Lehne Flash Cards

Common Drug Endings-cont’d

Common Drug Endings

Drug Classification

Drug Example

Drug Endings

Drug Classification

-tidine -prazole -cillin cef-, ceph-cycline -floxacin -thromycin -micin, mycin -azole -triptan -denafil, -dalafil -curium, -curonium

Histamine2 blocker-acid reducer Protein pump inhibitor-acid reducer Penicillin antibiotic Cephalosporin antibiotic Tetracycline antibiotic Fluoroquinolone antibiotic Macrolide antibiotic Aminoglycoside antibiotic Antifungal Serotonin-receptor agonists used for migraines PED5 inhibitors for erectile dysfunction Neuromuscular blockers used for muscle relaxation during surgery

Cimetidine Omeprazole Amoxicillin Cefazolin Tetracycline Levofloxacin Azithromycin Gentamicin Itraconazole Sumatriptan Sildenafil Pancuronium

-zosin -olol, -lol -zepam, -zolam

Alpha-adrenergic blocker used for HTN and BPH Prazosin Beta-adrenergic blocker (BB) Metoprolol Benzodiazepine (BZD) Diazepam, alprazolam Angiotensin-converting enzyme (ACE) inhibitor Lisinopril Angiotensin-receptor blocker (ARB) Candesartan Calcium channel blocker (CCB) Amlodipine Lipid-lowering drug Atorvastatin Thrombolytic used to dissolve clots Alteplase Anticoagulant Enoxaparin Corticosteroid Prednisone Bisphosphonate for osteoporosis Alendronate Bronchodilator used for asthma and COPD Albuterol

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Drug Endings

-pril -artan -dipine -statin -ase, -plase -parin -sone -dronate -terol

Drug Example

HTN, Hypertension; BPH, benign prostatic hypertrophy; COPD, chronic obstructive pulmonary disease; PED5, Phosphodiesterase type 5.

Continued

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Anticancer/Immunosuppressants drugs (methotrexate) Antiseizure drugs (carbamazepine, valproic acid, phenytoin, and others) Androgens (danazol, finasteride, dutasteride) ACE inhibitors (lisinopril and others) Angiotensin-receptor blockers (losartan and others) Antithyroid drugs (propylthiouracil, methimazole) Fluoroquinolone antibiotics (ciprofloxacin, levofloxacin) HMG-CoA reductase inhibitors [ie, statins] (atorvastatin and others) Isotretinoin (Accutane) used for acne Lithium used for bipolar disorder Nonsteroidal anti-inflammatory drugs (ibuprofen and others) Megadoses of vitamin A Tetracycline antibiotics (minocycline, doxycycline) Warfarin (Coumadin)

The risks for most drugs used in pregnancy have not been determined. (The benefits of treatment must balance the risks.) Category A: Remote risk of fetal harm Category B: Slightly more risk than A Category C: Greater risk than B Category D: Proven risk of fetal harm Category X: Proven risk of fetal harm

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 9 Drug Therapy During Pregnancy and Breast-Feeding

DRUGS THAT SHOULD BE AVOIDED DURING PREGNANCY BECAUSE OF PROVEN OR STRONGLY SUSPECTED TERATOGENICITY

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DRUGS THAT SHOULD BE AVOIDED DURING PREGNANCY BECAUSE OF PROVEN OR STRONGLY SUSPECTED TERATOGENICITY

Functions of Peripheral Adrenergic Receptor Subtypes

Receptor Subtype

Receptor Subtype

Response to Receptor Activation

Nicotinicn

All autonomic nervous system ganglia and the adrenal medulla

Alpha1

Nicotinicm Muscarinic

Neuromuscular junction All parasympathetic target organs: Eye Heart Lung

Stimulation of parasympathetic and sympathetic postganglionic nerves and release of epinephrine from the adrenal medulla Contraction of skeletal muscle Miosis (pupils constrict) Decreased rate Constriction of bronchi Promotion of secretions Voiding of the urinary bladder Salivation Increases gastric secretions, intestinal tone, and motility Defecation Generalized sweating Erection Vasodilation (BP decreases)

Alpha2

Bladder Gastrointestinal (GI) tract

Sweat glands Sex organs Blood vessels

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Location

Beta1

Beta2

Dopamine

Location

Response to Receptor Activation

Eye Arterioles and veins (skin, viscera, mucous membranes)

Mydriasis: “Wide eyed with fear” Constriction: (BP increases), blood is shunted away from the skin and viscera into skeletal muscle; “cold with fear” Sex organs, male Ejaculation Bladder neck and prostatic capsule Contraction Presynaptic nerve terminals Inhibition of transmitter release (NE): Decreased sympathetic nervous system (SNS) outflow to the blood vessels and heart reduces BP and pain Heart Increase in rate and force of contraction and in AV conduction velocity Kidney Release of renin to raise BP Arterioles (heart, lung, and skeletal Dilation increases blood flow to organs muscle) Bronchi Dilation improves oxygenation Uterus Relaxation prevents labor Liver Glycogenolysis increases blood glucose Skeletal muscle Enhanced contraction, glycogenolysis Kidney Dilation of kidney vasculature

CH 13 Physiology of he Peripheral Nervous System

Functions of Peripheral Cholinergic Receptor Subtypes

NE, Norepinephrine; AV, atrioventricular.

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MUSCARINIC AGONISTS Prototype: Bethanechol (Urecholine)

Mechanism of Action Activates muscarinic receptors Causes contraction of the detrusor muscle of the bladder and relaxation of the trigone and sphincter; the result is bladder emptying

Adverse Effects Hypotension due to vasodilation and bradycardia GI effects (excessive salivation, increased gastric acid, cramps, and diarrhea) Bladder rupture in patients with urinary obstruction Exacerbation of asthma due to bronchoconstriction Dysrhythmias in hyperthyroid patients due to reflex tachycardia

Cevimeline (Evoxac) for xerostomia (dry mouth) and inflammation of the cornea and conjunctiva Pilocarpine for topical therapy of glaucoma Muscarine is found in poisonous mushrooms Fold here

Uses Postoperative and postpartum urinary retention

Other Muscarinic Agonists

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 14 Muscarinic Agonists and Antagonists

MUSCARINIC AGONISTS Prototype: Bethanechol (Urecholine)

MUSCARINIC POISONING

Stimulation of muscarinic receptors causes profuse salivation, lacrimation (tearing), visual disturbances, bronchospasm, diarrhea, bradycardia, hypotension, and cardiovascular collapse

Sources of Muscarinic Poisoning

Treatment

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Ingestion of Inocybe and Clitocybe mushrooms Overdose with direct-acting muscarinic agonists (bethanechol, pilocarpine) Overdose with cholinesterase inhibitors (neostigmine [Prostigmin])

Ch 14 Muscarinic Agonists and Antagonists

MUSCARINIC POISONING Manifestation of Muscarinic Poisoning

Administration of atropine (a muscarinic blocking agent) Supportive care

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MUSCARINIC ANTAGONISTS (ANTICHOLINERGIC DRUGS) Prototype: Atropine

Prototype: Atropine Mechanism of Action

Other Muscarinic Antagonists

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Blocks muscarinic receptors Prevents receptor activation by endogenous acetylcholine Increases heart rate (tachycardia) Decreases salivary, bronchial, sweat, and acid-secreting cell secretions Relaxes bronchial smooth muscles (bronchodilation) Decreases bladder tone and GI motility (urinary retention) Dilates pupils (mydriasis) Cycloplegia (relaxation of the ciliary muscle) Mild central nervous system (CNS) excitation, hallucinations, and delirium

Drugs for an overactive bladder (eg, oxybutynin [Ditropan]) Scopolamine for motion sickness Ipratropium bromide (Atrovent) for COPD, rhinitis, and asthma Antisecretory anticholinergics (glycopyrrolate [Robinul]) Dicyclomine (Bentyl) for irritable bowel syndrome Centrally acting anticholinergics for Parkinson’s disease: (trihexyphenidyl [Artane] and benztropine [Cogentin])

Uses Preanesthesia to prevent bradycardia Dilation of pupil for ocular examination or surgery Treatment of bradycardia Intestinal hypertonicity and hypermotility for dysentery Antidote for muscarinic agonist poisoning

Adverse Effects Blurry vision, photophobia, increased intraocular pressure Urinary retention, dry mouth, constipation Anhidrosis and tachycardia (BUDCAT)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 14 Muscarinic Agonists and Antagonists

MUSCARINIC ANTAGONISTS (ANTICHOLINERGIC DRUGS)

ANTICHOLINERGIC SIDE EFFECTS B U D C A T

Other Drugs with Anticholinergic Side Effects Fold here

First-generation antihistamines (diphenhydramine [Benadryl]) Antiemetics (prochlorperazine [Compazine], promethazine [Phenergan]) First- and second-generation antipsychotic agents Tricyclic antidepressants (imipramine [Tofranil])

Ch 14 Muscarinic Agonists and Antagonists

ANTICHOLINERGIC SIDE EFFECTS B- blurry vision, photophobia, and increased intraocular pressure U- urinary retention D- dry mouth (xerostomia), decreased secretions C- constipation A- anhidrosis (absence of sweat) T- tachycardia

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ANTICHOLINERGIC DRUGS FOR OVERACTIVE BLADDER (OAB) Prototype: Oxybutynin (Ditropan, Ditropan XL, Oxytrol)

Mechanism of Action

Other Anticholinergic Drugs for OAB

Blocks muscarinic (M3) receptors in the bladder Inhibits bladder contractions and the urge to void

Adverse Effects

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Uses Overactive bladder (urge incontinence)

Darifenacin (Enablex) Solifenacin (Vesicare) Tolterodine (Detrol, Detrol LA) Trospium (Sanctura, Sanctura XR)

Blurry vision, photophobia, increased intraocular pressure Urinary retention, dry mouth, constipation Anhidrosis and tachycardia (BUDCAT) CNS effects

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 14 Muscarinic Agonists and Antagonists

ANTICHOLINERGIC DRUGS FOR OVERACTIVE BLADDER (OAB) Prototype: Oxybutynin (Ditropan, Ditropan XL, Oxytrol)

CHOLINESTERASE INHIBITORS Prototype: Neostigmine (Prostigmin)

Mechanism of Action

Other Reversible Cholinesterase Inhibitors

Prevents degradation of acetylcholine (ACh) ACh accumulates at neuromuscular junction Enhances effect of ACh to stimulate skeletal muscle contraction Muscarinic receptor activation Fold here

Uses Myasthenia gravis Reversal of neuromuscular blockade in postoperative patients Glaucoma, Alzheimer’s disease, and poisoning by muscarinic antagonists

Ambenonium (Mytelase) Pyridostigmine (Mestinon) Edrophonium (Tensilon) Physostigmine (Antilirium) for anticholinergic poisoning Echothiophate for treatment of glaucoma

Cholinesterase Inhibitors Used to Treat Alzheimer’s Disease Donepezil (Aricept) Galantamine (Razadyne) Rivastigmine (Exelon) Tacrine (Cognex)

Adverse Effects Excessive glandular secretions, increased GI motility Urinary urgency, bradycardia, sweating, and miosis Toxic doses reduce force of muscle contraction Cholinergic crisis—treat with atropine

Ch 15 Cholinesterase Inhibitors and Their Use in Myasthenia Gravis

CHOLINESTERASE INHIBITORS Prototype: Neostigmine (Prostigmin)

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NEUROMUSCULAR BLOCKERS Prototype: Succinylcholine (Anectine, Quelicin)

(Depolarizing neuromuscular blocker)

(Depolarizing neuromuscular blocker)

Mechanism of Action Causes paralysis of muscle by preventing repolarization (fasciculations)

Adverse Effects Prolonged paralysis in genetically determined individuals Hypotension Malignant hyperthermia—treat with dantrolene Hyperkalemia with cardiac arrest Muscle pain Antibiotics can intensify effect

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Uses Muscle relaxation during endotracheal intubation Short operative procedures Facilitation of mechanical ventilation Adjunct to electroconvulsive therapy Diagnosis of myasthenia gravis

Nondepolarizing Neuromuscular Blockers Atracurium (Tracrium) Cisatracurium (Nimbex) Pancuronium Rocuronium (Zemuron) Vecuronium (Norcuron)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 16 Drugs That Block Nicotinic Cholinergic Transmission

NEUROMUSCULAR BLOCKERS Prototype: Succinylcholine (Anectine, Quelicin)

ADRENERGIC AGONISTS Prototype: Epinephrine

Mechanism of Action

Other Adrenergic Agonists

Activates all four adrenergic receptors (alpha1, alpha2, beta1, and beta2) Pupil dilation, arterial and venous vasoconstriction Increases heart rate and force of contraction Bronchial dilation, glycogenolysis, enhanced muscle contraction Fold here

Uses Cardiac arrest, heart failure, anaphylactic shock AV heart block and asthma Delays absorption of local anesthetic and controls superficial bleeding Dilates pupil (mydriasis) for eye procedures

(Catecholamines and noncatecholamines) Norepinephrine (Levophed) Isoproterenol (Isuprel) Dopamine Dobutamine Phenylephrine Terbutaline Ephedrine

Ch 17 Adrenergic Agonists

ADRENERGIC AGONISTS Prototype: Epinephrine

Adverse Effects Hypertensive crisis, dysrhythmias, angina pectoris Necrosis after extravasation Hyperglycemia in diabetic patients

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ADRENERGIC AGONISTS Prototype: Phenylephrine

(Noncatecholamine)

(Noncatecholamine)

Mechanism of Action Activates alpha1 receptors Constricts blood vessels of the skin, viscera, and mucous membranes

Other Sympathomimetics Used for Nasal Congestion Oxymetazoline (Afrin) Pseudoephedrine (Sudafed)

Uses Fold here

Treatment of nasal congestion Delay of anesthetic absorption Dilation of the pupil for ocular exam

Adverse Effects Hypertension Necrosis

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 17 Adrenergic Agonists

ADRENERGIC AGONISTS Prototype: Phenylephrine

ALPHA-ADRENERGIC ANTAGONISTS Prototype: Prazosin (Minipress)

Mechanism of Action Blocks alpha1 receptors Dilates arteries and veins Relaxes smooth muscle in the bladder neck and prostatic capsule

Other Alpha Blockers

Uses Fold here

Essential hypertension Reversal of toxicity from alpha1 agonists Benign prostatic hyperplasia Pheochromocytoma Raynaud’s disease

Terazosin (Hytrin) Doxazosin (Cardura) Tamsulosin (Flomax) for BPH only Alfuzosin (Uroxatral) for BPH only Phentolamine for tissue necrosis

Ch 18 Adrenergic Antagonists

ALPHA-ADRENERGIC ANTAGONISTS Prototype: Prazosin (Minipress)

Adverse Effects Orthostatic hypotension, reflex tachycardia Nasal congestion Inhibition of ejaculation Use with sildenafil (Viagra) can lead to hypotension Sodium retention and increased blood volume Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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BETA-ADRENERGIC ANTAGONISTS First-Generation Nonselective Beta Blockers

Prototype: Propranolol (Inderal, InnoPran)

Prototype: Propranolol (Inderal, InnoPran)

Mechanism of Action

Uses Hypertension, angina pectoris, cardiac dysrhythmias Myocardial infarction, hyperthyroidism Migraine headache prophylaxis, “stage fright”

Other First-Generation Nonselective Beta Blockers

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Blocks beta1 and beta2 receptors Reduces heart rate, decreases force of ventricular contraction Decreases conduction through AV node, decreases cardiac output Suppresses secretion of renin Bronchoconstriction through beta2 blockade in the lung Reduces glycogenolysis through beta2 blockade in muscle and liver

Nadolol (Corgard) Sotalol (Betapace) for dysrhythmias Carvedilol (Coreg) blocks beta1, beta2, and alpha1 receptors Labetalol (Trandate) blocks beta1, beta2, and alpha1 receptors

Adverse Effects Bradycardia, AV heart block, heart failure Rebound cardiac excitation (tachycardia) after abrupt withdrawal Bronchoconstriction in asthmatics Inhibition of glycogenolysis, CNS effects mask tachycardia associated with hypoglycemia indicated in diabetics Avoid in patients with asthma, diabetes, depression, or severe allergies

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 18 Adrenergic Antagonists

BETA-ADRENERGIC ANTAGONISTS First-Generation Nonselective Beta Blockers

BETA-ADRENERGIC ANTAGONISTS Second-Generation Cardioselective Beta Blockers

Prototype: Metoprolol (Lopressor, Toprol XL)

Prototype: Metoprolol (Lopressor, Toprol XL) Other Cardioselective Beta Blockers

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Mechanism of Action Blocks cardiac beta1 receptors Reduces heart rate, decreases force of ventricular contraction Decreases conduction through AV node, decreases cardiac output Suppresses renin Minimal blockade of beta2 receptors (less bronchoconstriction) Not likely to inhibit glycogenolysis Preferred for patients with asthma or diabetes

Acebutolol (Sectral) Atenolol (Tenormin) Betaxolol (Kerlone) Bisoprolol (Zebeta) Esmolol (Brevibloc) for dysrhythmias

Ch 18 Adrenergic Antagonists

BETA-ADRENERGIC ANTAGONISTS Second-Generation Cardioselective Beta Blockers

Uses Hypertension, angina pectoris, heart failure Myocardial infarction Adverse Effects Bradycardia, reduction of cardiac output, AV heart block Rebound cardiac excitation (tachycardia) after abrupt withdrawal Masks tachycardia associated with hypoglycemia in diabetics

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BETA-ADRENERGIC ANTAGONISTS Third-Generation Vasodilating Alpha and Beta Blockers

Prototype: Labetalol (Normodyne, Trandate)

Prototype: Labetalol (Normodyne, Trandate)

Mechanism of Action Blocks alpha1 receptors on veins, causing vasodilation Blocks beta1 receptors in the heart and beta2 receptors in the lung Fold here

Uses Hypertension, hypertensive crisis

Other Alpha and Beta Blockers Carvedilol (Coreg) for heart failure (blocks beta1, beta2, and alpha1 receptors) Nebivolol (Bystolic) blocks beta receptors (promotes release of nitric acid, a vasodilator)

Adverse Effects Dizziness, orthostatic hypotension, ventricular dysrhythmias Nasal congestion, sexual dysfunction, bronchospasm

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 18 Adrenergic Antagonists

BETA-ADRENERGIC ANTAGONISTS Third-Generation Vasodilating Alpha and Beta Blockers

CENTRALLY ACTING ALPHA2 AGONISTS Prototype: Clonidine (Catapres)

Mechanism of Action

Other Alpha2 Agonists

Activates alpha2 receptors in the CNS Reduces sympathetic outflow to the heart and blood vessels Reduces stimulation of adrenergic receptors in the periphery Net effect of cardiac suppression and vasodilation is decreased blood pressure Fold here

Uses Hypertension Epidural infusion to relieve severe cancer pain

Guanabenz (Wytensin) Guanfacine (Tenex) Methyldopa* *Adverse

effects of methyldopa are hemolytic anemia and hepatotoxicity A positive Coombs’ test can occur with methyldopa

Adverse Effects

Ch 19 Indirect-Acting Antiadrenergic Agents

CENTRALLY ACTING ALPHA2 AGONISTS Prototype: Clonidine (Catapres)

Drowsiness and sedation Xerostomia (dry mouth) Hypotension Bradycardia, decrease in cardiac output Rebound hypertension in response to abrupt withdrawal Fetal harm Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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DOPAMINERGICS FOR PARKINSON’S DISEASE Prototype: Levodopa/Carbidopa (Sinemet)

Mechanism of Action Levodopa increases synthesis of dopamine in the striatum Carbidopa enhances effect of levodopa

Other Drugs That Increase Dopamine

Uses Reduces symptoms of Parkinson’s disease Fold here

Adverse Effects Effects take several months to develop Loss of effect occurs over time Nausea, vomiting, dyskinesias Postural hypotension, psychosis Dark sweat and urine, may activate melanoma

Pramipexole (Mirapex) Ropinirole (Requip) Entacapone (Comtan) Selegiline (Eldepryl) Amantadine (Symmetrel)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 21 Drugs for Parkinson’s Disease

DOPAMINERGICS FOR PARKINSON’S DISEASE Prototype: Levodopa/Carbidopa (Sinemet)

CHOLINESTRASE INHIBITORS FOR ALZHEIMER’S DISEASE Prototype: Donepezil (Aricept)

Mechanism of Action Prevents the breakdown of acetylcholine (ACh) Increases ACh at cholinergic synapses May slow progression of Alzheimer’s disease Minimal improvement of memory and cognitive function

Tacrine (Cognex) rarely used due to hepatotoxicity Rivastigmine (Exelon) Galantamine (Razadyne) Fold here

Uses Alzheimer’s disease

Other Cholinesterase Inhibitors

Adverse Effects Cholinergic effects Nausea, vomiting, dyspepsia, diarrhea Bradycardia Bronchoconstriction

Ch 22 Alzheimer’s Disease

CHOLINESTRASE INHIBITORS FOR ALZHEIMER’S DISEASE Prototype: Donepezil (Aricept)

Other Drugs for Alzheimer’s Disease Memantine (Namenda) N-methyl-D-aspartate (NMDA)–receptor antagonists for moderate to severe disease

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ANTIEPILEPTIC DRUGS (AEDs) Prototype: Phenytoin (Dilantin)

Mechanism of Action

Other AEDs

Inhibits entry of sodium into neurons Suppresses action potential of neurons

Uses Epilepsy Cardiac dysrhythmias

All AEDs may increase suicidal thoughts and behaviors

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Adverse Effects Nystagmus, sedation, ataxia, diplopia, cognitive impairment Gingival hyperplasia, rash, hirsutism, liver damage Fetal harm, bleeding tendencies in newborns Narrow therapeutic range (10 to 20 mcg/mL) Inject slowly (do not exceed 50 mg/minute) Dysrhythmias and hypotension if injected too fast Use normal saline to prevent precipitation Induces the metabolism of other drugs such as: oral contraceptives, warfarin, and glucocorticoids (drug effect is decreased) Withdraw over 6 to 8 weeks to prevent seizures

Carbamazepine (Tegretol) Valproic acid (Depakene, Depakote, Depacon) Ethosuximide (Zarontin) Phenobarbital Fosphenytoin (Cerebyx), a prodrug form of phenytoin

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Ch 24 Drugs for Epilepsy

ANTIEPILEPTIC DRUGS (AEDs) Prototype: Phenytoin (Dilantin)

ANTIEPILEPTIC DRUGS (AEDs) Prototype: Valproic Acid (Depakote)

Mechanism of Action

Newer Antiepileptic Drugs

Blocks sodium channels to suppress neurons Suppresses calcium influx Increases inhibitory influence of gamma-aminobutyric acid (GABA)

Uses Adverse Effects Nausea, vomiting, indigestion Hepatotoxicity, pancreatitis, fetal harm Weight gain, rash, hair loss, tremor Blood dyscrasias

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Epilepsy, bipolar disorder, migraine headaches

Oxcarbazepine (Trileptal) Lamotrigine (Lamictal) Gabapentin (Neurontin) Pregabalin (Lyrica) Levetiracetam (Keppra) Topiramate (Topamax) Tiagabine (Gabitril) Zonisamide (Zonegran) Felbamate (Felbatol) Vigabatrin (Sabril)

Ch 24 Drugs for Epilepsy

ANTIEPILEPTIC DRUGS (AEDs) Prototype: Valproic Acid (Depakote)

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MUSCLE RELAXANTS Prototype: Metaxalone (Skelaxin)

Mechanism of Action Unclear; sedative properties may cause relaxation

Other Centrally Acting Muscle Relaxants

Uses Relief of spasm resulting from muscle injury Fold here

Adverse Effects CNS depression Hepatotoxicity Physical dependence

Baclofen (Lioresal) Diazepam (Valium) Dantrolene Carisoprodol (Soma) Cyclobenzaprine (Flexeril, Fexmid) Cyclobenzaprine ER (Amrix) Chlorzoxazone (Paraflex, Parafon Forte, Remular-S) Methocarbamol (Robaxin) Orphenadrine (Norflex) Tizanidine (Zanaflex)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 25 Drugs for Muscle Spasm and Spasticity

MUSCLE RELAXANTS Prototype: Metaxalone (Skelaxin)

LOCAL ANESTHETICS Prototype: Lidocaine

Mechanism of Action

Other Local Anesthetics

Stops axonal conduction by blocking sodium channels in axonal membrane Stops nerve conduction

Procaine (Novocain) Bupivacaine (Marcaine)

Uses Surgical anesthesia Fold here

Adverse Effects Central nervous system excitation followed by depression Convulsions, respiratory depression Bradycardia, heart block, reduced contractile force Cardiac arrest, hypotension, allergic reactions

Ch 26 Local Anesthetics

LOCAL ANESTHETICS Prototype: Lidocaine

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GENERAL ANESTHETICS Inhaled Anesthetics

Mechanism of Action

Halothane (Fluothane) Isoflurane (Forane) Enflurane (Ethrane) Desflurane (Suprane) Sevoflurane (Ultane) Nitrous oxide

Enhance transmission at inhibitory synapses (GABA) Depress transmission at excitatory synapses (NMDA)

Uses Surgery Fold here

Adverse Effects Respiratory and cardiac depression Sensitization of the heart to catecholamines, leading to dysrhythmias Malignant hyperthermia—treat with dantrolene Aspiration of gastric contents Toxicity to operating room personnel Hepatotoxicity

Intravenous Anesthetics Thiopental sodium (Pentothal) Methohexital sodium (Brevital) Diazepam (Valium) Midazolam (Versed) Propofol (Diprivan) Etomidate (Amidate) Ketamine (Ketalar) Droperidol plus fentanyl (Innovar)

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Ch 27 General Anesthetics

GENERAL ANESTHESTICS

OPIOID ANALGESICS Prototype: Morphine

Mechanism of Action Activates mu receptors Produces analgesia, euphoria, sedation

Other Strong Opioid Agonists

Uses Relief of pain Fold here

Adverse Effects Respiratory depression, constipation Orthostatic hypotension, urinary retention, cough suppression Biliary colic, emesis, elevation of intracranial pressure Euphoria, dysphoria, sedation, miosis, neurotoxicity Tolerance and physical dependence Prolonged use affects hormone and immune functions Reversed with naloxone (Narcan)

Fentanyl (Sublimaze, Duragesic, Fentora, Actiq, Ionsys) Alfentanil (Alfenta) sufentanil (Sufenta) Remifentanil (Ultiva) Meperidine (Demerol) Methadone (Diskets, Dolophine, Methadose) Heroin Hydromorphone (Dilaudid) Oxymorphone (Opana) Levorphanol (Levo-Dromoran)

Moderate to Strong Opioid Agonists

Ch 28 Opioid (Narcotic) Analgesics and Antagonists

OPIOID ANALGESICS Prototype: Morphine

Codeine Oxycodone (OxyContin, Percodan, Percocet) Hydrocodone (Vicodin, Lortab) Propoxyphene (Darvon) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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AGONIST-ANTAGONIST OPIOIDS Prototype: Pentazocine (Talwin)

Mechanism of Action Acts as an agonist at kappa receptors and antagonist at mu receptors Produces analgesia and sedation Mild respiratory depression, increased cardiac work

Adverse Effects Physical dependence Unpleasant reactions (anxiety, strange thoughts, nightmares, hallucinations) If administered to a patient physically dependent on a pure opioid agonist, withdrawal syndrome can occur

Nalbuphine (Nubain) Butorphanol (Stadol) Buprenorphine (Buprenex, Subutex, Suboxone) Fold here

Uses Relief of mild to moderate pain

Other Partial Agonists

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Ch 28 Opioid (Narcotic) Analgesics and Antagonists

AGONIST-ANTAGONIST OPIOIDS Prototype: Pentazocine (Talwin)

OPIOID ANTAGONISTS Prototype: Naloxone (Narcan)

Mechanism of Action

Other Opioid Antagonists

Reverses the effects of opioids

Adverse Effects Minimal

Methylnaltrexone (Relistor) Nalmefene (Revex) Naltrexone (ReVia, Vivitrol) Fold here

Uses Reversal of opioid overdose Reversal of postoperative opioid effect Reversal of neonatal respiratory depression

Ch 28 Opioid (Narcotic) Analgesics and Antagonists

OPIOID ANTAGONISTS Prototype: Naloxone (Narcan)

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NONOPIOID CENTRALLY ACTING ANALGESICS Prototype: Tramadol (Ultram, Ultram ER)

Mechanism of Action Analog of codeine, weakly activates mu opioid receptors Blocks uptake of norepinephrine and serotonin Activates monoaminergic spinal inhibition of pain

Adverse Effects Mild sedation, dizziness, headache, dry mouth, constipation Increases the risk of seizure Minimal respiratory depression CNS depression if used with ETOH HTN if used with monoamine oxidase (MAO) inhibitors Serotonin syndrome if used with antidepressants or triptans Low potential for abuse; not a scheduled drug

Clonidine (Duraclon) Ziconotide (Prialt) Dexmedetomidine (Precedex) Fold here

Uses Relieves moderate to severe pain

Other Nonopioid Analgesics

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Ch 28 Opioid (Narcotic) Analgesics and Antagonists

NONOPIOID CENTRALLY ACTING ANALGESICS Prototype: Tramadol (Ultram, Ultram ER)

ERGOT ALKALOIDS Prototype: Ergotamine (Ergomar)

Mechanism of Action

Uses Migraine and cluster headaches

Other Ergot Alkaloids Dihydroergotamine (D.H.E. 45, Migranal) Ergotamine 1 caffeine (Cafergot, Ercaf)

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Alters transmission at serotonergic, dopaminergic, and alpha-adrenergic junctions Activates serotonin receptors Suppresses inflammation by blocking calcitonin gene–related peptide (CGRP) Promotes constriction

Ch 30 Drugs for Headache

ERGOT ALKALOIDS Prototype: Ergotamine (Ergomar)

Adverse Effects Nausea and vomiting Weakness in the legs, myalgias, tingling in the fingers and toes Angina-like pain Tachycardia or bradycardia Overdose can cause ergotism (ischemia due to constriction of vessels) Fetal harm Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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SEROTONIN1B/1D–RECEPTOR AGONISTS (TRIPTANS) Prototype: Sumatriptan (Imitrex)

Mechanism of Action Binds to 5-HT1B/1D (serotonin) receptors to cause vasoconstriction Reduces release of inflammatory peptides (CGRT) Diminishes perivascular inflammation Relieves migraine pain and associated symptoms

Adverse Effects

Fold here

Uses Migraine headache

Other Triptans Naratriptan (Amerge) Rizatriptan (Maxalt) Zolmitriptan (Zomig) Almotriptan (Axert) Frovatriptan (Frova) Eletriptan (Replax) Sumatriptan 1 naproxen (Treximet)

Chest symptoms (heavy arms and chest pressure) Coronary vasospasm Teratogenesis Vertigo, malaise, fatigue, tingling sensation

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 30 Drugs for Headache

SEROTONIN1B/1D–RECEPTOR AGONISTS (TRIPTANS) Prototype: Sumatriptan (Imitrex)

FIRST-GENERATION (CONVENTIONAL) ANTIPSYCHOTICS Prototype: Chlorpromazine (Thorazine)

Mechanism of Action

Other First-Generation Conventional Neuroleptics

Relieves positive symptoms of schizophrenia Blocks receptors for dopamine (D2), acetylcholine (ACh), histamine, and norepinephrine (NE)

Low Potency Chlorpromazine (Thorazine) Thioridazine (Mellaril)

Uses

Adverse Effects

Fold here

Schizophrenia, bipolar disorder, Tourette’s syndrome Prevention of emesis, and dementia

Medium Potency Loxapine (Loxitane) Molindone (Modan) Pherphenazine

Extrapyramidal symptoms (EPS) (acute dystonia, parkinsonism, akathisia, tardive dyskinesia) Neuroleptic malignant syndrome (lead pipe rigidity, high fever, autonomic instability) Anticholinergic effects (BUDCAT), orthostatic hypotension Sedation, neuroendocrine effects, seizures Sexual dysfunction, increased risk of sunburn Agranulocytosis, dysrhythmias (prolongs QT interval) Counteracts the effect of levodopa used in Parkinson’s disease Rate of mortality doubles when used in elderly patients with dementia Increases prolactin levels Cut here

Haloperidol (Haldol), Haldol Decanoate (depot preparation) Fluphenazine (Prolixin Decanoate [depot preparation]) Trifluoperazine, Thiothixene (Navane) Pimozide (Orap)

SECOND-GENERATION (ATYPICAL) ANTIPSYCHOTICS Prototype: Clozapine (Clozaril)

SECOND-GENERATION (ATYPICAL) ANTIPSYCHOTICS Prototype: Clozapine (Clozaril)

High Potency

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Other Second-Generation (Atypical) Antipsychotics

Fold here

Risperidone (Risperdal) Risperdal Consta (depot preparation) Paliperidone (Invega) Olanzapine (Zyprexa) Quetiapine (Seroquel) Ziprasidone (Geodon) Aripiprazole (Abilify)

Adverse Effects Agranulocytosis Metabolic effects (weight gain, diabetes, dyslipidemia) Seizures, myocarditis, orthostatic hypotension Rate of mortality doubles when used in elderly patients with dementia Sedation, weight gain, anticholinergic effects (BUDCAT) Lower risk of extrapyramidal effects Costs 10 times more than conventional agents Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 31 Antipsychotic Agents and Their Use in Schizophrenia

Mechanism of Action Relieves positive, negative, and cognitive signs and symptoms of schizophrenia Blocks receptors for serotonin (5-HT), D2, ACh, histamine, and NE Uses Schizophrenia Levodopa-induced psychosis Bipolar disorder

Ch 31 Antipsychotic Agents and Their Use in Schizophrenia

FIRST-GENERATION (CONVENTIONAL) ANTIPSYCHOTICS Prototype: Chlorpromazine (Thorazine)

TRICYCLIC ANTIDEPRESSANTS (TCAs) Prototype: Imipramine (Tofranil)

Mechanism of Action

Other TCAs

Inhibits reuptake of norepinephrine (NE) and serotonin (more serotonin and NE are available at the synapse)

Fold here

Uses Depression, bipolar disorder, neuropathic pain Chronic insomnia Attention deficit/hyperactivity disorder Panic disorder, obsessive-compulsive disorder (OCD)

Amitriptyline Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Sinequan) Maprotiline Nortriptyline (Aventyl, Pamelor) Protriptyline (Vivactil) Trimipramine (Surmontil)

Ch 32 Antidepressants

TRICYCLIC ANTIDEPRESSANTS (TCAs) Prototype: Imipramine (Tofranil)

Adverse Effects Orthostatic hypotension, anticholinergic effects (BUDCAT) Diaphoresis (sweating), sedation Cardiotoxicity, seizures, hypomania Increased risk of suicide, especially in younger individuals Many drug interactions Selective serotonin reuptake inhibitors (SSRIs) preferred for treatment of depression Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) Prototype: Fluoxetine (Prozac, Sarafem)

Mechanism of Action Inhibits serotonin reuptake (more serotonin is available at the synapse)

Other SSRIs

Adverse Effects Sexual dysfunction, nausea, headache, insomnia Weight gain, serotonin syndrome Withdrawal syndrome Neonatal abstinence syndrome and persistent pulmonary hypertension Teratogenesis Increased risk of suicide Extrapyramidal side effects Bruxism (clenching and grinding of the teeth) Decrease in platelet aggregation, leading to bleeding Hyponatremia

Fold here

Uses Major depression, bipolar disorder Obsessive-compulsive disorder Panic disorder, bulimia nervosa Premenstrual dysphoric disorder

Paroxetine (Paxil, Paxil CR, Pexeva) Fluvoxamine (Luvox) Sertraline (Zoloft) Citalopram (Celexa) Escitalopram (Lexapro)

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Ch 32 Antidepressants

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) Prototype: Fluoxetine (Prozac, Sarafem)

SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) Prototype: Venlafaxine (Effexor)

Mechanism of Action

Other SNRIs

Blocks norepinephrine (NE) and 5-HT uptake; weak blockade of dopamine uptake (more transmitter available at synapse)

Major depression, generalized anxiety disorder Social anxiety disorder (social phobia)

Adverse Effects

Fold here

Uses

Duloxetine (Cymbalta) (indicated for physical pain and diabetic neuropathy; can cause liver toxicity) Desvenlafaxine (Pristiq)

Nausea, headache, anorexia, nervousness, sweating, somnolence, and insomnia Weight loss, diastolic hypertension Sexual dysfunction, hyponatremia Increased risk of suicide Intense withdrawal syndrome with abrupt discontinuation (anxiety, agitation, tremors, headache, vertigo, nausea, tachycardia, tinnitus) Neonatal withdrawal syndrome Serotonin syndrome Fetal harm

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MONOAMINE OXIDASE INHIBITORS (MAOIs) Prototype: Isocarboxazid (Marplan)

Mechanism of Action Increases NE and serotonin by blocking the enzyme that inactivates them

Other MAOIs Phenelzine (Nardil) Tranylcypromine (Parnate) Transdermal selegiline (Emsam)

Uses Atypical depression, bulimia nervosa, OCD, and panic attacks Fold here

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Ch 32 Antidepressants

MONOAMINE OXIDASE INHIBITORS (MAOIs) Prototype: Isocarboxazid (Marplan)

Adverse Effects CNS stimulation (anxiety, insomnia, agitation, hypomania, and mania) Orthostatic hypotension due to vasodilation Hypertensive crisis from high levels of dietary tyramine Many drug interactions SSRIs preferred for treatment of depression

Ch 32 Antidepressants

SEROTONIN/NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) Prototype: Venlafaxine (Effexor)

ATYPICAL ANTIDEPRESSANTS Prototype: Bupropion (Wellbutrin, Zyban)

Mechanism of Action

Other Atypical Antidepressants Nefazodone (can cause liver failure) Mirtazapine (Remeron) Amoxapine Reboxetine Trazodone (Desyrel) has sedative effects

Unclear; may be related to blockade of dopamine uptake

Fold here

Uses Major depressive disorder Prevention of seasonal affective disorder (SAD) Smoking cessation Relief of neuropathic pain (unlabeled use) Attention deficit/hyperactivity disorder (unlabeled use)

Ch 32 Antidepressants

ATYPICAL ANTIDEPRESSANTS Prototype: Bupropion (Wellbutrin, Zyban)

Adverse Effects Risk of seizure May increase the risk of suicide Agitation, headache, dry mouth, constipation, weight loss, GI upset, dizziness, tremor, insomnia, blurred vision, and tachycardia

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MOOD-STABILIZING DRUGS Prototype: Lithium (Lithobid, Lithonate, Lithotabs)

Mechanism of Action Mechanism unclear; may alter ions and neurotransmitters May protect against neuronal atrophy and/or promote neuronal growth

Other Mood-Stabilizing Drugs Antiepileptic Drugs Valproic acid Carbamazepine Lamotrigine (Lamictal)

Uses

Adverse Effects Accumulates to toxic levels in the presence of a low sodium level Lithium levels must be kept below 1.5 mEq/L Blood levels are drawn 12 hours after evening dose Signs of toxicity include fine hand tremor, GI upset, thirst, polyuria, and muscle weakness Chronic use can lead to renal toxicity and hypothyroidism FDA Pregnancy Risk Category D Reversible leukocytosis, dermatologic reactions Drug interactions occur with diuretics, NSAIDs, and anticholinergics

Fold here

Stabilizes mood in patients with bipolar disorder Reduces euphoria, hyperactivity, and other symptoms Preferred for patients with classic (euphoric) mania

Atypical Antipsychotics Olanzapine (Zyprexa) Aripiprazole (Abilify) Ziprasidone (Geodon)

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Ch 33 Drugs for Bipolar Disorder

MOOD-STABILIZING DRUGS Prototype: Lithium (Lithobid, Lithonate, Lithotabs)

MOOD-STABILIZING ANTIEPILEPTIC DRUGS Prototype: Valproic Acid (Depakote)

Mechanism of Action

Other AEDs used for BPD

Suppresses mania and stabilizes mood

Carbamazepine (Equetro, Tegretol)—monitor CBC Lamotrigine (Lamictal)

Uses Mood stabilizer for patients with bipolar disorder Fold here

Adverse Effects GI disturbances, weight gain Thrombocytopenia, pancreatitis, liver failure Target trough level is 50 to 120 mg/mL Fetal harm

Ch 33 Drugs for Bipolar Disorder

MOOD-STABILIZING ANTIEPILEPTIC DRUGS Prototype: Valproic Acid (Depakote)

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Mechanism of Action Depresses central nervous system function Reduces anxiety, promotes sleep Potentiates the actions of GABA (an inhibitory neurotransmitter)

Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Estazolam (ProSom) Flurazepam (Dalmane) Lorazepam (Ativan) Midazolam (Versed) Oxazepam (Serax) Quazepam (Doral) Temazepam (Restoril) Triazolam (Halcion)

Uses Anxiety, insomnia, seizure disorder, induction of anesthesia Muscle spasm, panic disorder, and withdrawal from alcohol Adverse Effects CNS depression, anterograde amnesia Sleep driving and other complex sleep-related behaviors Paradoxic effects Weak respiratory depression if given orally IV administration can cause severe respiratory depression Abuse and addiction, teratogenic Do not mix with other CNS depressants or alcohol Reversal agent is flumazenil (Romazicon)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 34 Sedative-Hypnotic Drugs

BENZODIAZEPINES (BZDs) Prototype: Alprazolam (Xanax)

Fold here

BENZODIAZEPINES (BZDs) Prototype: Alprazolam (Xanax)

BENZODIAZEPINE-LIKE DRUGS Prototype: Zolpidem (Ambien)

Mechanism of Action

Other BZD-like drugs

Potentiate the actions of GABA (an inhibitory neurotransmitter)

Zaleplon (Sonata) Eszopiclone (Lunesta)

Uses Short-term management of insomnia Fold here

Adverse Effects Daytime drowsiness, dizziness Sleep driving and other complex sleep-related behaviors Do not use with alcohol or other CNS depressants

Melatonin Agonist Ramelteon (Rozerem)

Ch 34 Sedative-Hypnotic Drugs

BENZODIAZEPINE-LIKE DRUGS Prototype: Zolpidem (Ambien)

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BARBITURATES CNS Depressants

Mechanism of Action Potentiate the actions of GABA (an inhibitory neurotransmitter)

Thiopental Secobarbital Phenobarbital

Uses

Adverse Effects Respiratory depression, decreased blood pressure and heart rate Induction of hepatic drug-metabolizing enzymes (increases the metabolism of other drugs rendering them less effective) May lead to tolerance and dependence Frequently used as vehicles for suicide Teratogenic

Miscellaneous Sedative-Hypnotics Fold here

Insomnia Suppression of seizures, induction of general anesthesia Treatment of manic states

Chloral hydrate (Aquachloral Supprettes, Somnote) Meprobamate (Miltown) Paraldehyde (Paral) Trazodone (Desyrel) antidepressant Diphenhydramine (Sominex) Doxylamine (Unisom)

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Ch 34 Sedative-Hypnotic Drugs

BARBITURATES CNS Depressants

CNS STIMULANTS Prototype: Methylphenidate (Ritalin, Metadate, Concerta, Daytrana)

Mechanism of Action Promotes norepinephrine (NE) and dopamine (DA) release Inhibits NE and DA reuptake

Other CNS Stimulants

Adverse Effects

Fold here

Uses Attention deficit/hyperactivity disorder (ADHD) Narcolepsy

Dexmethylphenidate (Focalin) Dexedrine Adderall Modafinil (Provigil) Atomoxetine (Strattera)—nonstimulant

Insomnia, reduced appetite, weight loss Palpitations, hypertension, angina, dysrhythmias, psychosis Abrupt discontinuation can lead to withdrawal reactions Potential for abuse (Schedule II) Sudden death

Ch 36 CNS Stimulants and Attention-Deficit/Hyperactivity Disorder

CNS STIMULANTS Prototype: Methylphenidate (Ritalin, Metadate, Concerta, Daytrana)

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DISULFIRAM (ANTABUSE) Aversion Therapy for Alcoholism

Mechanism of Action Disrupts alcohol metabolism by blocking enzyme Acetaldehyde accumulates and produces unpleasant effects Uses Alcohol abuse Fold here

Adverse Effects Nausea, vomiting, flushing, palpitations, headache Sweating, blurry vision, hypotension, chest pain Shock occurs with ingestion of 7 mL of alcohol

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Ch 38 Drug Abuse II: Alcohol

DISULFIRAM (ANTABUSE) Aversion Therapy for Alcoholism

HIGH-CEILING (LOOP) DIURETICS Prototype: Furosemide (Lasix)

Mechanism of Action

Other High-Ceiling Diuretics

Blocks reabsorption of sodium and chloride in the descending limb of Henle’s loop to promote urination Produces profound diuresis

Ethacrynic acid (Edecrin) Bumetanide (Bumex) Torsemide (Demadex)

Ch 40 Diuretics

HIGH-CEILING (LOOP) DIURETICS Prototype: Furosemide (Lasix)

Uses Fold here

Rapid mobilization of fluid Pulmonary edema resulting from heart failure or renal or liver disease Especially useful in patients with renal insufficiency

Adverse Effects Hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia Ototoxicity, hyperglycemia, hyperuricemia, fetal harm Raises LDL and lowers HDL (minimally) May cause dysrhythmias when used with digoxin (reduces potassium)

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THIAZIDE DIURETICS Prototype: Hydrochlorothiazide (HCTZ)

Mechanism of Action Blocks reabsorption of sodium and chloride in the early segment of the distal convoluting tubule to promote urination

Other Thiazides and Related Diuretics Chlorothiazide (Diuril) Methyclothiazide (Enduron) Chlorthalidone (Hygroton, Thalitone) Metolazone (Zaroxolyn)

Uses

Adverse Effects

Fold here

Treatment of hypertension Mobilization of edema with mild heart failure, hepatic or renal disease Ineffective when GFR is low (,15 to 20 mL/min)

Hyponatremia, hypochloremia, dehydration Hypokalemia, magnesium deficiency, and hypotension Hyperglycemia, hyperuricemia, increase in LDL and triglycerides May cause dysrhythmias when used with digoxin (reduces potassium) Fetal harm

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Ch 40 Diuretics

THIAZIDE DIURETICS Prototype: Hydrochlorothiazide (HCTZ)

POTASSIUM-SPARING DIURETICS Prototype: Spironolactone (Aldactone)

Mechanism of Action

Other Potassium-Sparing Diuretics

Blocks the actions of aldosterone in the distal nephron Produces minimal diuresis Causes retention of potassium and increased excretion of sodium

Other Aldosterone Blockers Fold here

Uses Hypertension and edema Used in combination with other diuretics to counterbalance potassium loss Heart failure (Blocks the negative effects of aldosterone on the heart and blood vessels) Primary hyperaldosteronism, premenstrual syndrome Polycystic ovary syndrome, and acne

Triamterene (Dyrenium) Amiloride (Midamor)

Ch 40 Diuretics

POTASSIUM-SPARING DIURETICS Prototype: Spironolactone (Aldactone)

Eplerenone (Inspra) Not considered a diuretic Used for heart failure

Adverse Effects Hyperkalemia, dysrhythmias Endocrine effects (Gynecomastia, menstrual irregularities, impotence, and hirsutism) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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OSMOTIC DIURETICS Prototype: Mannitol (Osmitrol)

Mechanism of Action Creates an osmotic force in the lumen of the nephron Promotes diuresis by inhibiting passive reabsorption of water Uses

Adverse Effects Edema CHF and pulmonary edema

Fold here

Prophylaxis of renal failure Reduction of intracranial pressure Reduction of intraocular pressure

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 40 Diuretics

OSMOTIC DIURETICS Prototype: Mannitol (Osmitrol)

ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS Prototype: Ramipril (Altace)

Mechanism of Action Inhibits ACE, reducing levels of angiotensin II Dilates arterioles and veins to reduce blood volume and BP Prevents pathologic changes in cardiac structure Fold here

Uses Hypertension, heart failure, MI Diabetic and nondiabetic nephropathy Prevention of MI, stroke, and death

Other ACE Inhibitors

Adverse Effects Hypotension, cough, hyperkalemia Renal failure in patients with renal artery stenosis Fetal injury Angioedema Neutropenia, dysgeusia, and rash with captopril

Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil and Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Trandolapril (Mavik)

Ch 43 Drugs Acting on the Renin-Angiotensin-Aldosterone System

ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS Prototype: Ramipril (Altace)

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ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) Prototype: Losartan (Diovan)

Mechanism of Action Blocks the action of angiotensin II Dilates arterioles and veins to reduce blood volume and BP Prevents pathologic changes in cardiac structure Does not cause cough or significant hyperkalemia Fold here

Uses Hypertension, heart failure, MI, and diabetic nephropathy Prevention of MI, stroke, and death

Other ARBs Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avalide) Losartan (Hyzaar) Olmesartan (Benicar) Telmisartan (Micardis)

Adverse Effects Renal failure in patients with renal artery stenosis Hypotension Angioedema Fetal harm

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Ch 43 Drugs Acting on the Renin-Angiotensin-Aldosterone System

ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) Prototype: Losartan (Diovan)

DIRECT RENIN INHIBITORS (DRIs) Prototype: Aliskiren (Tekturna)

Mechanism of Action Binds with renin and inhibits the formation of angiotensin I

Uses Hypertension Fold here

Adverse Effects Angioedema and cough GI effects (diarrhea) Hyperkalemia Fetal injury and death

Ch 43 Drugs Acting on the Renin-Angiotensin-Aldosterone System

DIRECT RENIN INHIBITORS (DRIs) Prototype: Aliskiren (Tekturna)

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ALDOSTERONE ANTAGONISTS Prototype: Eplerenone (Inspra)

Mechanism of Action Blocks aldosterone, increases excretion of sodium and water Retention of potassium Reduces blood volume and blood pressure Prevents cardiovascular remodeling

Adverse Effects Hyperkalemia

Spironolactone

Fold here

Uses Hypertension, heart failure

Other Aldosterone Antagonists

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Ch 43 Drugs Acting on the Renin-Angiotensin-Aldosterone System

ALDOSTERONE ANTAGONISTS Prototype: Eplerenone (Inspra)

CALCIUM CHANNEL BLOCKERS Nondihydropyridines

Prototypes: Verapamil (Calan) and Diltiazem (Cardizem)

Prototypes: Verapamil (Calan) and Diltiazem (Cardizem)

Mechanism of Action

Fold here

Block calcium channels in the heart and blood vessels Dilate peripheral arterioles to reduce blood pressure Increase coronary perfusion Block SA and AV nodes to reduce heart rate and contractility Reduce force of myocardial contraction

Ch 44 Calcium Channel Blockers

CALCIUM CHANNEL BLOCKERS Nondihydropyridines

Uses Angina, essential hypertension, cardiac dysrhythmias Adverse Effects Constipation, dizziness, facial flushing, peripheral edema, hypotension Bradycardia, AV block, decreased cardiac contractility Chronic eczematous rash and gingival hyperplasia Verapamil increases digoxin level by 60% Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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CALCIUM CHANNEL BLOCKERS Dihydropyridine

Prototype: Amlodipine (Norvasc)

Prototype: Amlodipine (Norvasc)

Mechanism of Action

Uses Hypertension Angina

Other Dihydropyridine Calcium Channel Blockers

Fold here

Blocks calcium channels in the blood vessels Little effect on heart rate or contractility Vasodilation in peripheral arterioles lowers blood pressure Calcium channel blockade in coronary arteries increases perfusion

Nifedipine (Adalat, Procardia) Nicardipine (Cardene) Isradipine (DynaCirc) Felodipine (Plendil) Nimodipine (Nimotop) Nisoldipine (Sular)

Adverse Effects Hypotension, edema, flushing, dizziness, headache Peripheral edema, gingival hyperplasia, chronic eczematous rash Does not slow heart rate, as do verapamil and diltiazem

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Ch 44 Calcium Channel Blockers

CALCIUM CHANNEL BLOCKERS Dihydropyridine

VASODILATORS Prototype: Hydralazine (Apresoline)

Mechanism of Action

Other Vasodilators

Selective dilation of arterioles (mechanism unknown) Decrease in peripheral resistance and arterial blood pressure Increase in heart rate and myocardial contractility by reflex

Uses Adverse Effects Reflex tachycardia Increased blood volume Systemic lupus erythematosus–like syndrome Headache, dizziness, weakness, and fatigue

Fold here

Essential hypertension, hypertensive crisis, heart failure

BiDil (hydralazine and isosorbide dinitrate) Minoxidil Diazoxide (Hyperstat IV) Sodium nitroprusside (Nitropress) Angiotensin-converting enzymes (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Direct renin inhibitors (DRIs) Calcium channel blockers (CCBs) Alpha-adrenergic blocking agents Ganglionic blocking agents Adrenergic neuron blocking agents Centrally acting alpha2 agonists Nesiritide (Natrecor) Drugs used for pulmonary artery hypertension

Ch 45 Vasodilators

VASODILATORS Prototype: Hydralazine (Apresoline)

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CARDIAC (DIGITALIS) GLYCOSIDES Prototype: Digoxin (Lanoxin)

Positive Inotropic Agent for Heart Failure

Positive Inotropic Agent for Heart Failure

Mechanism of Action

Uses

Other Drugs Used to Treat Heart Failure

Fold here

Increases the force of ventricular contraction to increase cardiac output Inhibits Na1, K1-ATPase to increase Ca11 inside myocytes Competes with K1 for binding to Na1, K1-ATPase ↓ K → ↑ Na1, K1-ATPase inhibition → digoxin toxicity Changes electrical activity of heart and slows heart rate Increased cardiac output → decreased sympathetic tone, increased urine production, and decreased release of renin

Diuretics ACE inhibitors Angiotensin receptor blockers Beta blockers Aldosterone blockers

Heart failure and dysrhythmias

Adverse Effects Anorexia, nausea and vomiting, fatigue Visual disturbances (blurry vision, yellow tinge, halos) Dysrhythmias Digoxin toxicity (therapeutic level, 0.5 to 0.8 ng/mL) Hold if HR , 60 bpm or K1 is low Inject slowly over 5 minutes Give Digibind for digoxin overdose

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Ch 47 Drugs for Heart Failure

CARDIAC (DIGITALIS) GLYCOSIDES Prototype: Digoxin (Lanoxin)

CLASS I: SODIUM CHANNEL BLOCKERS Prototype: Procainamide (Procanbid)

Class IA Sodium Channel Blocker

Class IA Sodium Channel Blocker

Mechanism of Action Blocks cardiac sodium channels Slows conduction in the atria, ventricles, and His-Purkinje system Delays depolarization

Quinidine Disopyramide (Norpace) Fold here

Uses Atrial and ventricular dysrhythmias

Other Class IA Sodium Channel Blockers

Ch 48 Antidysrhythmic Drugs

CLASS I: SODIUM CHANNEL BLOCKERS Prototype: Procainamide (Procanbid)

Adverse Effects Systemic lupus erythematosus–like syndrome Blood dyscrasias QRS widening and prolongation

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CLASS I: SODIUM CHANNEL BLOCKERS Class IB Sodium Channel Blocker

Prototype: Lidocaine (Xylocaine)

Prototype: Lidocaine (Xylocaine)

Mechanism of Action

Uses Short-term therapy for ventricular dysrhythmias

Adverse Effects No significant impact on the ECG Drowsiness, confusion, and paresthesias Toxic doses may produce convulsions and respiratory arrest

Other Sodium Channel–Blocking Antidysrhythmics

Fold here

Blocks cardiac sodium channels Slows conduction in the atria, ventricles, and His-Purkinje system Reduces automaticity in the ventricles and His-Purkinje system Accelerates repolarization

Class IB Mexiletine (Mexitil) Phenytoin (Dilantin) Class IC Flecainide (Tambocor) Propafenone (Rythmol)

Other Class I Moricizine (Ethmozine)

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Ch 48 Antidysrhythmic Drugs

CLASS I: SODIUM CHANNEL BLOCKERS Class IB Sodium Channel Blocker

CLASS II: BETA BLOCKERS Prototype: Propranolol (Inderal)

Mechanism of Action

Uses Sinus tachycardia, severe recurrent ventricular tachycardia Exercise-induced tachydysrhythmias Paroxysmal atrial tachycardia provoked by emotion or exercise Angina of effort

Other Class II Agents Acebutolol (Sectral) Esmolol (Brevibloc)

Fold here

Nonselective beta-adrenergic antagonist Attenuates sympathetic stimulation of the heart Blocks both beta1 and beta2 receptors Reduces automaticity of the SA node Reduces velocity of conduction through the AV node (prolongs PR interval) Reduces myocardial contractility

Ch 48 Antidysrhythmic Drugs

CLASS II: BETA BLOCKERS Prototype: Propranolol (Inderal)

Adverse Effects Prolongs PR interval on the ECG Bradycardia, heart failure, AV block, and sinus arrest Hypotension, bronchospasm in patients with asthma Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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CLASS III: POTASSIUM CHANNEL BLOCKERS Prototype: Amiodarone (Cordarone, Pacerone)

Mechanism of Action

Other Class III Agents

Delays repolarization Reduces automaticity in the SA node, reduces contractility Reduces conduction velocity in the AV node, ventricles, and His-Purkinje system Dilates coronary and peripheral blood vessels

Bretylium Sotalol (Betapace) class II and class III Dofetilide (Tikosyn) Ibutilide (Corvert)

Uses

Adverse Effects Pulmonary toxicities (pneumonitis and fibrosis) Widening of the QRS complex, prolongation of the PR and QT intervals Sinus bradycardia, AV block, precipitation of heart failure, hypotension Toxicities in pregnancy Corneal microdeposits, optic neuropathy Blue-gray discoloration of the skin GI reactions (anorexia, nausea, vomiting) CNS reactions (ataxia, dizziness, tremor, mood alterations, hallucinations) Hepatitis, thyroid dysfunction Grapefruit juice increases levels to toxicity

Fold here

Recurrent ventricular fibrillation Unstable ventricular tachycardia

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Ch 48 Antidysrhythmic Drugs

CLASS III: POTASSIUM CHANNEL BLOCKERS Prototype: Amiodarone (Cordarone, Pacerone)

CLASS IV: CALCIUM CHANNEL BLOCKERS Prototypes: Verapamil (Calan, Isoptin, Verelan) Diltiazem (Cardizem, others)

Mechanism of Action Block calcium channels in the heart Slow SA node automaticity, delay AV node conduction Reduce myocardial contractility

Adenosine (Adenocard) Digoxin (Lanoxin) Fold here

Uses Atrial fibrillation or atrial flutter Supraventricular tachycardia

Other Antidysrhythmic Drugs

Ch 48 Antidysrhythmic Drugs

CLASS IV: CALCIUM CHANNEL BLOCKERS Prototypes: Verapamil (Calan, Isoptin, Verelan) Diltiazem (Cardizem, others)

Adverse Effects Bradycardia, AV block, and heart failure Hypotension, peripheral edema, and constipation Can elevate digoxin levels Grapefruit juice increases levels to toxicity

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HMG-CoA REDUCTASE INHIBITORS (STATINS) Prototype: Atorvastatin (Lipitor)

Mechanism of Action

Uses Hypercholesterolemia Primary and secondary prevention of CV events Post MI therapy Prevention of CV events in people with diabetes

Other “Statins”

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Inhibits the enzyme (HMG-CoA) that synthesizes cholesterol Increases the number of LDL receptors on liver cells to remove more LDL Decreases production of VLDLs and raises HDL levels Stabilizes plaque, slows progression of coronary calcification Improves endothelial function Enhances the ability of blood vessels to dilate Reduces the risk of thrombosis Inhibits platelet deposition and aggregation May increase bone formation

Fluvastatin (Lescol) Lovastatin (Mevacor, Altoprev) Pravastatin (Pravachol) Rosuvastatin (Crestor) Simvastatin (Zocor) Cholestin (dietary supplement made from red yeast)

Adverse Effects Headache, rash, GI complaints Myopathy, increases CK levels, rhabdomyolysis, dark urine, renal failure Hepatotoxicity, increases ALT and AST Rare peripheral neuropathy FDA Pregnancy risk Category X

Drug Interactions Macrolide antibiotics, azole antifungals HIV protease inhibitors, amiodarone, cyclosporine, and grapefruit juice raise some statins to toxic levels

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 49 Prophylaxis of Coronary Heart Disease

HMG-CoA REDUCTASE INHIBITORS (STATINS) Prototype: Atorvastatin (Lipitor)

NICOTINIC ACID Prototype: Nicotinic Acid (Niacor, Niaspan)

Mechanism of Action

Drug Combinations

Reduces LDL and triglycerides Increases HDL

Fold here

Uses Lowers triglycerides in patients at risk for pancreatitis Dyslipidemia Reduces the risk of major coronary events Reduces total mortality

Lovastatin/niacin (Advicor) Simvastatin/niacin (Simcor)

Adverse Effects

Ch 49 Prophylaxis of Coronary Heart Disease

NICOTINIC ACID Prototype: Nicotinic Acid (Niacor, Niaspan)

Flushing and itching (take 325 mg ASA 30 minutes before dose) Gastric upset, nausea, vomiting, diarrhea Hepatotoxicity May raise blood sugar in patients with diabetes May increase incidence of gout

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BILE-ACID SEQUESTRANTS Prototype: Colesevelam (WelChol)

Mechanism of Action Binds (sequesters) bile acids in the GI tract Prevents the absorption and promotes their excretion Forms insoluble complex with bile acids Increases LDL receptors Safest of all lipid-lowering drugs

Cholestyramine (Questran) Colestipol (Colestid)

Fold here

Uses Hypercholesterolemia Often used in combination with statin Approved to control hyperglycemia in patients with type 2 diabetes

Other Agents

Adverse Effects Constipation, bloating, indigestion Interferes with absorption of other drugs May impede absorption of fat-soluble vitamins

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 49 Prophylaxis of Coronary Heart Disease

BILE-ACID SEQUESTRANTS Prototype: Colesevelam (WelChol)

EZETIMIBE (ZETIA) Cholesterol-Lowering Drug

Mechanism of Action

Drug Combinations

Inhibits cholesterol absorption in the small intestine Reduces LDL, triglycerides, and apolipoprotein B Small increase in HDL

Simvastatin/ezetimibe (Vytorin)

Uses

Adverse Effects Reports of myopathy, rhabdomyolysis, pancreatitis, and thrombocytopenia May increase risk of liver damage when used with statins

Fold here

Hypercholesterolemia Used in combination with statins

Ch 49 Prophylaxis of Coronary Heart Disease

EZETIMIBE (ZETIA) Cholesterol-Lowering Drug

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FIBRIC ACID DERIVATIVES (FIBRATES) Prototype: Gemfibrozil (Lopid)

Mechanism of Action Reduces triglycerides by lowering VLDL Raises HDL levels

Other Fibric Acid Derivatives Fenofibrate (TriCor, Antara, Lofibra, Triglide) Fenofibric acid (TriLipix)—approved for use with statins

Uses Hypertriglyceridemia Fold here

Adverse Effects Rash, nausea, abdominal pain, diarrhea Gallstone formation Myopathy, liver injury Increases warfarin levels, leading to hemorrhage Do not combine gemfibrozil with statins

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 49 Prophylaxis of Coronary Heart Disease

FIBRIC ACID DERIVATIVES (FIBRATES) Prototype: Gemfibrozil (Lopid)

ORGANIC NITRATES (ANTIANGINAL AGENTS) Prototype: Nitroglycerin

Mechanism of Action

Similar Agents

Dilates veins, decreases venous return to the heart Reduces ventricular filling and wall tension (preload) Reduces cardiac oxygen demand

Isosorbide mononitrate Isosorbide dinitrate Amyl nitrite

Uses Adverse Effects Headache, orthostatic hypotension Reflex tachycardia Tolerance to drug effect Vasospasm if withdrawn abruptly Use with sildenafil (Viagra), other drugs for erectile dysfunction may lead to severe hypotension

Other Antianginal Agents Fold here

Angina, myocardial infarction

Ch 50 Drugs for Angina Pectoris

ORGANIC NITRATES (ANTIAGINAL AGENTS) Prototype: Nitroglycerin

Beta blockers Calcium blockers Ranolazine (Ranexa)

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ANTICOAGULANTS Prototype: Heparin

Mechanism of Action

Low-Molecular-Weight Heparins (LMWH)

Suppresses the formation of fibrin in veins Inactivates clotting factors thrombin and Xa Anticoagulant effect develops quickly

Enoxaparin (Lovenox) Dalteparin (Fragmin) Tinzaparin (Innohep) LMWH can be given on a fixed dose; does not require aPTT monitoring

Uses

Monitor Activated partial thromboplastin time (aPTT) Normal aPTT: 40 seconds; therapeutic level: 60 to 80 seconds

Adverse Effects Bleeding—antidote is protamine sulfate Heparin-induced thrombocytopenia (HIT) Decreased platelet count (,100,000/mm3) leads to thrombosis Hypersensitivity reaction (fever, chills, urticaria) May be used during pregnancy

Fold here

Used for pulmonary embolism, evolving stroke, DVT Open heart surgery, renal dialysis Prevention of postoperative thrombosis Disseminated intravascular coagulation Acute myocardial infarction

Selective Factor Xa Inhibitors Fondaparinux (Arixtra) Rivaroxaban (Xarelto)

Direct Thrombin Inhibitors Bivalirudin (Angiomax) Lepirudin (Refludan) Argatroban Desirudin (Ipravask)

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Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

ANTICOAGULANTS Prototype: Heparin

ANTICOAGULANT Prototype: Warfarin (Coumadin, Jantoven)

Mechanism of Action

Oral Anticoagulant

Suppresses coagulation by reducing production of clotting factors Antagonizes vitamin K Inhibits vitamin K–dependent clotting factors Blocks synthesis of factors VII, IX, X, and prothrombin Effect takes a few days

Uses Fold here

Long-term prophylaxis of venous thrombosis and pulmonary embolism Prevention of thromboembolism in patients with mechanical heart valves Prevention of thrombosis in patients with atrial fibrillation Prevention of transient ischemic attacks and recurrent MI

Monitor Prothrombin time (PT)—reported as INR Goal INR for atrial fibrillation: 2-3 Goal INR for mechanical valves: 3-4.5

Adverse Effects Hemorrhage—antidote is vitamin K (phytonadione) Skin disorders, GI disturbances, red-orange color of urine Increased risk of fractures with long-term use Many drug-drug interactions Keep intake of vitamin K foods constant Fetal harm

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ANTIPLATELET DRUGS Prototype: Aspirin

Mechanism of Action Irreversible inhibition of COX-1 and COX-2 Suppresses platelet aggregation Decreases prostaglandin synthesis Reduces the risk of arterial thrombosis Reduces inflammation, pain, and fever Fold here

Uses

Adverse Effects Gastric distress (heartburn and nausea) GI bleeding, gastric ulceration and perforation Not used in children because of the risk of Reye’s syndrome Fetal harm (prolongs labor, premature closure of the patent ductus) Salicylism (tinnitus, sweating, headache, dizziness) Hypersensitivity in patients with allergies Renal impairment Bleeding

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

ANTIPLATELET DRUGS Prototype: Aspirin

Ischemic stroke, transient ischemic attacks (TIAs) Chronic stable angina, unstable angina Coronary stenting, acute MI, previous MI Primary prevention of MI

Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

ANTICOAGULANT Prototype: Warfarin (Coumadin, Jantoven)

ANTIPLATELET DRUGS ADENOSINE DIPHOSPHATE RECEPTOR (ADP) ANTAGONISTS Prototype: Clopidogrel (Plavix)

Mechanism of Action

Other, Similar Agent

Blocks ADP receptors so that platelets are unable to aggregate

Adverse Effects Dyspepsia, diarrhea, rash Intracranial hemorrhage, GI bleeding Rare thrombotic thrombocytopenia (TTP)

Fold here

Uses Prevents blockage of coronary artery stints Reduces thrombotic events—MI, ischemic stroke, vascular death

Ticlopidine (Ticlid)—major adverse effects

Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

ANTIPLATELET DRUGS ADENOSINE DIPHOSPHATE RECEPTOR (ADP) ANTAGONISTS Prototype: Clopidogrel (Plavix)

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ANTIPLATELET DRUGS GLYCOPROTEIN llb/llla–RECEPTOR ANTAGONISTS Prototype: Abciximab (RePro)

Mechanism of Action

Other, Similar Agents

Causes reversible blockade of platelet GP IIb/IIIa receptors Interferes with the final step in platelet aggregation

Adverse Effects Hemorrhage

Fold here

Uses Prevents ischemic events in patients with acute coronary syndrome Used during percutaneous angioplasty

Eptifibatide (Integrilin) Tirofiban (Aggrastat) Dipyridamole (Persantine) Cilostazol (Pletal)

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Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

ANTIPLATELET DRUGS GLYCOPROTEIN llb/llla–RECEPTOR ANTAGONISTS Prototype: Abciximab (RePro)

THROMBOLYTIC DRUGS Prototype: Alteplase (tPA)

Mechanism of Action

Other, Similar Agents

Converts plasminogen to plasmin Plasmin is an enzyme that digests the fibrin matrix of clots Dissolves existing thrombi Does not prevent thrombi from forming

Adverse Effects Bleeding Intracranial hemorrhage

Fold here

Uses Acute myocardial infarction, pulmonary embolism, and ischemic stroke

Streptokinase (Streptase) Tenecteplase (TNKase) Reteplase (Retavase) Urokinase (Abbokinase)

Ch 51 Anticoagulant, Antiplatelet, and Thrombolytic Drugs

THROMBOLYTIC DRUGS Prototype: Alteplase (tPA)

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FERROUS SULFATE Oral Iron Preparation

Mechanism of Action Essential to the function of hemoglobin and myoglobin (oxygen-storing molecule of muscle)

Other Oral Iron Preparations Ferrous fumarate Ferrous gluconate Carbonyl iron

Uses Iron deficiency anemia (microcytic hypochromic anemia) Fold here

Adverse Effects Nausea, heartburn (pyrosis), bloating, constipation, diarrhea May turn stool dark green or black Liquid iron preparation stains teeth Toxic to children (lethal dose is 2 to 10 grams)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 54 Drugs for Deficiency Anemias

FERROUS SULFATE Oral Iron Preparation

CYANOCOBALAMIN (VITAMIN B12)

Mechanism of Action Essential for synthesis of DNA Catalyzes conversion of folic acid to its active form Uses B12 deficiency, pernicious anemia Macrocytic normochromic anemia (megaloblastic anemia) Fold here

Adverse Effects Hypokalemia Never given IV Folic acid can mask the hematologic effects of B12 deficiency

Ch 54 Drugs for Deficiency Anemias

CYANOCOBALAMIN (VITAMIN B12)

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FOLIC ACID (FOLATE)

Mechanism of Action Essential for synthesis of DNA

Uses Treatment of folic acid deficiency (megaloblastic anemia) Used prophylactically to prevent neural tube defects (NTDs) Adverse Effects Fold here

Does not correct neurologic consequences Can correct anemia but may mask B12 deficiency Always give folic acid with B12

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 54 Drugs for Deficiency Anemias

FOLIC ACID (FOLATE)

ERYTHROPOIETIC GROWTH FACTORS Prototype: Epoetin Alfa (Erythropoietin, Epogen, Procrit)

Mechanism of Action Stimulates production of red blood cells in the bone marrow

Other Erythropoietic Growth Factors Darbepoetin Alpha (Aranesp)—long acting Methoxy polyethylene glycol (Mircera) Fold here

Uses Anemia of chronic renal failure Anemia due to AIDS treatment with AZT (zidovudine) Anemia caused by chemotherapy Anemia in patients facing surgery

Ch 55 Hematopoietic Growth Factors

ERYTHROPOIETIC GROWTH FACTORS Prototype: Epoetin Alfa (Erythropoietin, Epogen, Procrit)

Adverse Effects Hypertension Increase in cardiovascular events (heart failure, thrombosis, stroke and MI) Hemoglobin level should not exceed 12 g/dL Rise in hemoglobin should not exceed 1 g/dL in 2 weeks Red cell aplasia (anemia due to autoimmune response)

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LEUKOPOIETIC GROWTH FACTORS Prototype: Filgrastim (Neupogen)

Mechanism of Action Acts on bone marrow to increase production of neutrophils

Other Leukopoietic Growth Factors Pegfilgrastim (Neulasta) Sargramostim (Leukine)

Fold here

Uses Patients undergoing myelosuppressive chemotherapy Patients undergoing bone marrow transplantation Harvesting of peripheral blood progenitor cells Severe chronic neutropenia Reduces risk of infection Adverse Effects Bone pain, leukocytosis Elevates uric acid levels, LDH, and alkaline phosphatase Splenomegaly

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 55 Hematopoietic Growth Factors

LEUKOPOIETIC GROWTH FACTORS Prototype: Filgrastim (Neupogen)

THROMBOPOIETIC GROWTH FACTORS Prototype: Oprelvekin (Neumega)

Mechanism of Action Stimulates production of platelets (thrombocytes)

Uses Patients undergoing myelosuppressive chemotherapy Increases platelets to minimize thrombocytopenia Fold here

Adverse Effects Retention of sodium and water by kidneys Peripheral edema Tachycardia, atrial fibrillation, atrial flutter Severe allergic reactions Conjunctival injection

Ch 55 Hematopoietic Growth Factors

THROMBOPOIETIC GROWTH FACTORS Prototype: Oprelvekin (Neumega)

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ORAL AGENTS FOR TYPE 2 DIABETES BIGUANIDES Prototype: Metformin (Glucophage, Fortamet, Glumetza, Riomet)

Mechanism of Action

Uses Type 2 diabetes Prevention of type 2 diabetes Treatment of polycystic ovary syndrome (PCOS)

Fold here

Inhibits glucose production in the liver (gluconeogenesis) Inhibits glucose absorption in the intestines Sensitizes insulin receptors on fat and skeletal muscle Enhances glucose uptake and metabolism by muscle Lowers basal and postprandial blood sugar

Adverse Effects Decreased appetite, nausea, diarrhea, and weight loss Rare cases of lactic acidosis Avoid in patients with renal disease (Cr .1.4 mg/dL) Avoid in patients with ethyl alcohol (ETOH) abuse, infection, liver disease, or CHF Discontinue 48 hours prior to test with contrast medium to avoid lactic acidosis Can reduce vitamin B12 and folic acid absorption

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES BIGUANIDES Prototype: Metformin (Glucophage, Fortamet, Glumetza, Riomet)

ORAL AGENTS FOR TYPE 2 DIABETES SULFONYLUREAS Prototype: Glipizide (Glucotrol, Glucotrol ER)

Mechanism of Action Stimulates insulin release from the pancreas

Other Sulfonylureas Glyburide (DiaBeta, Micronase) Glimepiride (Amaryl)

Uses Type 2 diabetes Fold here

Adverse Effects Hypoglycemia Possible increased risk of sudden cardiac death Fetal harm Disulfiram-like reaction when taken with ETOH

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES SULFONYLUREAS Prototype: Glipizide (Glucotrol, Glucotrol ER)

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ORAL AGENTS FOR TYPE 2 DIABETES MEGLITINIDES Prototype: Repaglinide (Prandin)

Mechanism of Action

Other Meglitinide

Stimulates pancreatic insulin release

Nateglinide (Starlix)

Uses Type 2 diabetes Fold here

Adverse Effects Hypoglycemia Administer 30 minutes before a meal

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES MEGLITINIDES Prototype: Repaglinide (Prandin)

ORAL AGENTS FOR TYPE 2 DIABETES THIAZOLIDINEDIONES (GLITAZONES, TZDs) Prototype: Rosiglitazone (Avandia)

Mechanism of Action Increases insulin sensitivity

Other TZDs Pioglitazone (Actos)

Uses Type 2 diabetes Fold here

Adverse Effects Mild headache and upper respiratory infections Raises LDL levels Fluid retention—caution in patients with CHF Hepatotoxicity—monitor ALT May increase cardiovascular events

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES THIAZOLIDINEDIONES (GLITAZONES, TZDs) Prototype: Rosiglitazone (Avandia)

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ORAL AGENTS FOR TYPE 2 DIABETES ALPHA-GLUCOSIDASE INHIBITORS Prototype: Acarbose (Precose)

Mechanism of Action

Other Alpha-Glucosidase Inhibitor

Delays absorption of carbohydrates Lowers postprandial blood glucose levels

Adverse Effects Flatulence, cramps, abdominal distention, and diarrhea Hypoglycemia, liver dysfunction

Fold here

Uses Type 2 diabetes

Miglitol (Glyset)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES ALPHA-GLUCOSIDASE INHIBITORS Prototype: Acarbose (Precose)

Uses Type 2 diabetes

Fold here

Mechanism of Action Increases the incretin system Inhibits the enzyme DPP-4, which breaks down incretin hormones Suppresses glucagon release from the alpha cells of the pancreas Stimulates insulin release from the beta cells of the pancreas Turns off glucose production in the liver

ORAL AGENTS FOR TYPE 2 DIABETES GLIPTINS Prototype: Sitagliptin (Januvia)

Ch 56 Drugs for Diabetes Mellitus

ORAL AGENTS FOR TYPE 2 DIABETES GLIPTINS Prototype: Sitagliptin (Januvia)

Adverse Effects Nasal inflammation, upper respiratory tract infection Minimal hypoglycemia

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NEW INJECTABLE DRUGS FOR DIABETES INCRETIN MIMETIC Prototype: Exenatide (Byetta)

Mechanism of Action

Uses Type 2 diabetes

Fold here

Action similar to natural incretins released in the GI tract Slows gastric emptying Stimulates glucose-dependent release of insulin Inhibits postprandial release of glucagon Suppresses appetite Decreases postprandial blood glucose

Adverse Effects Hypoglycemia Nausea, vomiting, and diarrhea Rare incidences of pancreatitis Weight loss Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 56 Drugs for Diabetes Mellitus

NEW INJECTABLE DRUGS FOR DIABETES INCRETIN MIMETIC Prototype: Exenatide (Byetta)

Uses

Fold here

Mechanism of Action Mimics the effects of amylin (hormone made in the pancreas) Reduces postprandial levels of glucose Delays gastric emptying Suppresses glucagon secretion Increases the sense of satiety Enhances the effects of mealtime insulin

NEW INJECTABLE DRUGS FOR DIABETES AMYLIN MIMETIC Prototype: Pramlintide (Symlin)

Ch 56 Drugs for Diabetes Mellitus

NEW INJECTABLE DRUGS FOR DIABETES AMYLIN MIMETIC Prototype: Pramlintide (Symlin)

Type 1 and type 2 diabetes

Adverse Effects Hypoglycemia when combined with other agents Nausea Injection site reactions

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INJECTABLE DRUGS FOR DIABETES GLUCAGON

Mechanism of Action Hormone that increases plasma levels of glucose Opposite effect of insulin Uses

Adverse Effects Nausea and vomiting Place patient on side after administration

Fold here

Treats hypoglycemia from insulin overdose Used only if intravenous glucose is not available

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Ch 56 Drugs for Diabetes Mellitus

INJECTABLE DRUGS FOR DIABETES GLUCAGON

THYROID HORMONES Prototype: Levothyroxine (Synthroid, Levoxyl)

Synthetic Preparation of T4

Synthetic Preparation of T4

Mechanism of Action Converted to T3 in the body Thyroid hormone replacement

Other Thyroid Hormone Preparations

Adverse Effects Thyrotoxicosis if dosage is excessive Tachycardia, angina, nervousness, insomnia Hyperthermia, sweating, and tremor Increases warfarin levels Takes about 1 month to reach plateau Take on an empty stomach Do not mix with calcium or iron

Fold here

Uses Hypothyroidism

Liothyronine (Cytomel, Triostat) T3 Liotrix (Thyrolar) T3, T4 combination Armour Thyroid—desiccated animal thyroid glands

Ch 57 Drugs for Thyroid Disorders

THYROID HORMONES Prototype: Levothyroxine (Synthroid, Levoxyl)

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ANTITHYROID DRUGS Prototype: Propylthiouracil (PTU)

Mechanism of Action Inhibits thyroid hormone synthesis Inhibits conversion of T4 to T3 in the periphery

Other Antithyroid Drugs

Uses

Adverse Effects Agranulocytosis, hypothyroidism Fetal harm, rash, nausea, arthralgia, headache Dizziness, paresthesias, and liver injury May take 6 to 12 months to develop

Fold here

Hyperthyroidism, Graves’ disease Thyrotoxic crisis

Methimazole (Tapazole) Radioactive iodine (131I) Nonradioactive iodine—(Lugol’s solution) Sodium iodide (IV) Potassium iodide (Thyro-Block) Propranolol (Inderal) suppresses tachycardia

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Ch 57 Drugs for Thyroid Disorders

ANTITHYROID DRUGS Prototype: Propylthiouracil (PTU)

ERECTILE DYSFUNCTION DRUGS PDE-5 Inhibitors

Prototype: Sildenafil (Viagra)

Prototype: Sildenafil (Viagra)

Mechanism of Action Enhances the normal erectile response to sexual stimuli by inhibiting PDE-5

Other Erectile Dysfunction Drugs

Adverse Effects Hypotension, priapism Nonarteritic ischemic optic neuropathy (NAION) Sudden hearing loss, dizziness, vertigo, tinnitus Headache, flushing, dyspepsia, nasal congestion Visual changes (blue color tinge, light sensitivity, blurring) Use with nitrates and alpha blockers leads to hypotension

Fold here

Uses Erectile dysfunction

Tadalafil (Cialis) Vardenafil (Levitra) Papaverine plus phentolamine injection Alprostadil (prostaglandin E1)

Ch 65 Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia

ERECTILE DYSFUNCTION DRUGS PDE-5 Inhibitors

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DRUGS FOR BENIGN PROSTATIC HYPERTROPHY (BPH) 5-alpha-Reductase Inhibitors

Prototype: Finasteride (Proscar)

Prototype: Finasteride (Proscar)

Mechanism of Action

Other 5-alpha Reductase Inhibitor

Reduces levels of dihydrotestosterone (DHT) Promotes regression of prostate epithelial tissue Reduces mechanical obstruction of the urethra Fold here

Adverse Effects Reduces ejaculate volume and libido Gynecomastia (breast enlargement) Reduces prostate-specific antigen (PSA) May mask an elevated PSA Benefits develop slowly over 6 to 12 months

Dutasteride (Avodart)

Alpha1-Adrenergic Antagonists Terazosin (Hytrin) Doxazosin (Cardura) Tamsulosin (Flomax)—used for BPH only Alfuzosin (Uroxatral)—used for BPH only Other Drugs for BPH Saw palmetto Tolterodine (Detrol) PDE-5 inhibitors Botox Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 65 Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia

DRUGS FOR BENIGN PROSTATIC HYPERTROPHY (BPH) 5-alpha-Reductase Inhibitors

Oral Polio Vaccine (OPV) not used in the United States Measles, Mumps, and Rubella Virus Vaccine (MMR) Live Influenza Attenuated Vaccine (LIAV)

Ch 67 Childhood Immunization

LIVE VIRUS VACCINES Varicella (Varivax)

LIVE VIRUS VACCINES Live virus vaccines are contraindicated in pregnancy Give with caution in immunocompromised patients

Fold here

Yellow fewer vaccine Zoster vaccine (Zostavax) Rotavirus vaccine (Rotarix, Rota Teq)

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IMMUNOSUPPRESSANTS Prototype: Cyclosporine (Sandimmune, Gengraf, Neoral)

Mechanism of Action

Other Immunosuppressants

Suppresses production of inflammatory cells Reduces B cells and cytotoxic T cells

Uses Adverse Effects Nephrotoxicity, infection, hepatotoxicity, lymphomas Hypertension, tremor, hirsutism, leukopenia Gingival hyperplasia, gynecomastia Anaphylaxis, fetal harm

Fold here

Prevents rejection of organ transplants

Tacrolimus (Prograf) Sirolimus (Rapamune) Glucocorticoids Cytotoxic drugs Antibodies

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Ch 68 Immunosuppressants

IMMUNOSUPPRESSANTS Prototype: Cyclosporine (Sandimmune, Gengraf, Neoral)

FIRST-GENERATION H1 ANTAGONISTS Antihistamines

Prototype: Diphenhydramine (Benadryl)

Prototype: Diphenhydramine (Benadryl)

Uses Seasonal allergic rhinitis, urticaria, severe allergy, motion sickness, insomnia Cold symptoms, sleep aid, mild transfusion reactions, allergic reactions

Other First-Generation Antihistamines

Fold here

Mechanism of Action Blocks H1 receptors Blocks some muscarinic receptors Reduces actions of histamine Reduces flushing, itching, and secretion of mucus

Ch 69 Antihistamines

FIRST-GENERATION H1 ANTAGONISTS Antihistamines

Brompheniramine Chlorpheniramine (Chlor-Trimeton) Dexchlorpheniramine Clemastine (Tavist) Promethazine (Phenergan) Hydroxyzine (Vistaril)

Adverse Effects Sedation, confusion, fatigue Paradoxical excitation can occur Gastrointestinal disturbances Anticholinergic effects (BUDCAT) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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SECOND-GENERATION (NONSEDATING) H1 ANTAGONISTS Prototype: Loratadine (Claritin)

Antihistamine

Antihistamine

Uses Allergic rhinitis, urticaria, and mild transfusion reactions

Other Second-Generation Nonsedating H1 Antagonists Fold here

Mechanism of Action Blocks H1 receptors Reduces actions of histamine Reduces flushing, itching, secretion of mucus Does not cross brain-blood barrier to cause sedation

Desloratadine (Clarinex) Fexofenadine (Allegra) Cetirizine (Zyrtec) Levocetirizine (Xyzal) Azelastine (Astelin) nasal spray

Adverse Effects Reduce dose if hepatic or renal impairment occurs Cetirizine (Zyrtec) may cause mild sedation in some patients

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Ch 69 Antihistamines

SECOND-GENERATION (NONSEDATING) H1 ANTAGONISTS Prototype: Loratadine (Claritin)

CYCLOOXYGENASE INHIBITORS Nonsteroidal Anti-inflammatory Drug (NSAID) Prototype: Aspirin

Mechanism of Action Irreversible inhibition of cyclooxygenase (COX-1 and COX-2) Suppresses platelet aggregation Decreases prostaglandin synthesis Reduces inflammation, pain, and fever

Uses Fold here

Suppression of inflammation Analgesia Reduction of fever in adults Dysmenorrhea Suppression of platelet aggregation to protect against MI and stroke Prevention of colorectal cancer Possible protection against Alzheimer’s disease

Adverse Effects Gastric distress (heartburn and nausea) GI bleeding, gastric ulceration and perforation Not used in children because of the risk of Reye’s syndrome Fetal harm (prolongs labor, premature closure of the patent ductus) Salicylism (tinnitus, sweating, headache, dizziness) Hypersensitivity in patients with allergies Renal impairment Bleeding

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CYCLOOXYGENASE INHIBITORS First Generation—Nonaspirin NSAIDs Prototype: Ibuprofen (Advil, Motrin)

Prototype: Ibuprofen (Advil, Motrin)

Other NSAIDs

Mechanism of Action Reversible inhibition of COX-1 and COX-2 Inhibits prostaglandin synthesis Has anti-inflammatory, analgesic, and antipyretic actions

Adverse Effects Bleeding, gastric ulceration, renal impairment Cross-hypersensitivity with aspirin May precipitate Reye’s syndrome Fetal harm Risk of MI and stroke

Fold here

Uses

Fenoprofen (Nalfon) Flurbiprofen (Ansaid) Ketoprofen Naproxen (Aleve, Anaprox, Naprelan, Naprosyn) Oxaprozin (Daypro) Diclofenac (Voltaren, Cataflam)—risk of liver failure Voltaren Gel and Flector Patch Diclofenac Plus Misoprostol (Arthrotec) Diflunisal (Dolobid) Etodolac Indomethacin (Indocin) Ketorolac (Toradol), available IM or IV Mefenamic acid (Ponstel) Meclofenamate Meloxicam (Mobic) Nabumetone Piroxicam (Feldene) Sulindac (Clinoril) Tolmetin (Tolectin) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 70 Cyclooxygenase Inhibitors: NSAIDs and Acetaminophen

CYCLOOXYGENASE INHIBITORS First Generation—Nonaspirin NSAIDs

Fever, pain, arthritis, dysmenorrhea Closure of the ductus arteriosus in preterm infants

Ch 70 Cyclooxygenase Inhibitors: NSAIDs and Acetaminophen

CYCLOOXYGENASE INHIBITORS Nonsteroidal Anti-inflammatory Drug (NSAID) Prototype: Aspirin

CYCLOOXYGENASE INHIBITOR Second-Generation NSAID (COX-2 Inhibitor)

Prototype: Celecoxib (Celebrex)

Prototype: Celecoxib (Celebrex)

Uses

Fold here

Mechanism of Action Selective inhibition of COX-2 Decreases prostaglandin synthesis at the site of injury Reduces pain and inflammation Spares COX-1 inhibition Minimal gastric, renal, and platelet effect Osteoarthritis, rheumatoid arthritis, dysmenorrhea Acute pain

Adverse Effects Dyspepsia, mild renal impairment Not used in patients with sulfonamide allergy Premature closure of ductus arteriosus No inhibition of platelets Increased risk of MI and stroke

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ACETAMINOPHEN (TYLENOL) Analgesic and Antipyretic

Mechanism of Action Reduces prostaglandin synthesis in the CNS Has no anti-inflammatory properties Uses Fold here

Adverse Effects Toxic metabolite builds up in ETOH abusers Hepatic necrosis can occur Maximum dose is 4 grams/day Acetylcysteine (Mucomyst) given for overdose Inhibits metabolism of warfarin (risk of bleeding)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 70 Cyclooxygenase Inhibitors: NSAIDs and Acetaminophen

ACETAMINOPHEN (TYLENOL) Analgesic and Antipyretic

Pain and fever Preferred in children No GI injury, no effect on platelets or kidneys

Ch 70 Cyclooxygenase Inhibitors: NSAIDs and Acetaminophen

CYCLOOXYGENASE INHIBITOR Second-Generation NSAID (COX-2 Inhibitor)

GLUCOCORTICOIDS Short Acting

Mechanism of Action Suppress immune responses and inflammation Inhibit prostaglandins, leukotrienes, and histamine Suppress phagocytes and lymphocytes

Intermediate Acting

Fold here

Uses Rheumatoid arthritis, SLE, inflammatory bowel disease Bursitis, osteoarthritis, anaphylaxis, asthma Skin disorders, neoplasms, suppression of allograft rejection Prevention of respiratory distress syndrome (RDS) in preterm infants Replacement therapy for patients with Addison’s disease

Cortisone Hydrocortisone

Prednisone Prednisolone Methylprednisone Triamcinolone

Long Acting Betamethasone Dexamethasone

Adverse Effects Adrenal insufficiency resulting from suppression of HPA axis Osteoporosis, infection, glucose intolerance (increases blood sugar) Myopathy, sodium and water retention, potassium loss Growth retardation, mood changes Cataracts, glaucoma Peptic ulcer disease, iatrogenic Cushing’s syndrome Fetal harm

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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Blocks conversion of folic acid to its active form Reduces joint destruction, retards disease progression Takes 3 to 5 months to see effect

Sulfasalazine (Azulfidine) Leflunomide (Arava) Hydroxychloroquine (Plaquenil)

Uses Rheumatoid arthritis, non-Hodgkin’s lymphoma Lymphocytic leukemia, psoriasis, and Crohn’s disease

DMARDs II

Adverse Effects

Fold here

Mechanism of Action

DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDs I) Prototype: Methotrexate (Rheumatrex, Trexall) Other DMARDs I

Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Rituximab (Rituxan) Abatacept (Orencia)

DMARDs III Penicillamine (Cuprimine) Azathioprine (Imuran) Cyclosporine Anakinra (Kineret) Protein A column (Prosorba) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 72 Drug Therapy of Rheumatoid Arthritis

DISEASE-MODIFYING ANTIRHEUMATIC DRUGS (DMARDs I) Prototype: Methotrexate (Rheumatrex, Trexall)

Bone marrow suppression, hepatic fibrosis GI ulceration, pneumonitis, and fetal harm

Ch 71 Glucocorticoids in Nonendocrine Diseases

GLUCOCORTICOIDS

DRUGS FOR HYPERURICEMIA Prototype: Allopurinol (Zyloprim)

Mechanism of Action

Other Drugs for Hyperuricemia

Inhibits uric acid formation

Adverse Effects Hypersensitivity syndrome Nausea, vomiting, abdominal discomfort Drowsiness, headache, metallic taste Cataracts with prolonged use (.3 years)

Probenecid Sulfinpyrazone (Anturane)

Drugs for Acute Gouty Arthritis Fold here

Uses Chronic tophaceous gout Hyperuricemia secondary to chemotherapy Not useful for acute gouty attacks

Ch 73 Drug Therapy of Gout

DRUGS FOR HYPERURICEMIA Prototype: Allopurinol (Zyloprim)

NSAIDs Glucocorticoids Colchicine (GI toxicities)

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BISPHOSPHONATES Prototype: Alendronate (Fosamax)

Mechanism of Action Suppresses resorption of bone Reduces both the number and activity of osteoclasts

Other Bisphosphonates

Uses

Adverse Effects Esophagitis Musculoskeletal pain, ocular problems Osteonecrosis of the jaw Atrial fibrillation

Fold here

Postmenopausal osteoporosis Osteoporosis in men Glucocorticoid-induced osteoporosis Paget’s disease of the bone

Risedronate (Actonel) Ibandronate (Boniva) Tiludronate (Skelid) Etidronate (Didronel) Zoledronate (Reclast, Zometa)

Other Drugs Used to Treat Osteoporosis Selective Estrogen Receptor Modulators (SERMs) Raloxifene (Evista) Parathyroid Hormone Teriparatide (Forteo)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 74 Drugs Affecting Calcium Levels and Bone Mineralization

BISPHOSPHONATES Prototype: Alendronate (Fosamax)

ANTI-INFLAMMATORY DRUGS FOR ASTHMA INHALED CORTICOSTEROIDS (ICSs) Prototype: Fluticasone Propionate (Flovent)

Mechanism of Action

Uses

Other Inhaled Corticosteroids

Fold here

Suppresses the inflammation of asthma Decreases leukotrienes, histamine, and prostaglandins Decreases eosinophils and leukocytes Reduces edema of the airway and mucus production Reduces bronchial hyperactivity Increases number of beta2 receptors Increases responsiveness to beta2 agonists

Beclomethasone dipropionate (QVAR) Budesonide (Pulmicort Turbohaler, Pulmicort Respules) Flunisolide (AeroBid) Mometasone furoate (Asmanex Twisthaler) Triamcinolone acetonide (Azmacort)

Ch 75 Drugs for Asthma

ANTI-INFLAMMATORY DRUGS FOR ASTHMA INHALED CORTICOSTEROIDS (ICSs) Prototype: Fluticasone Propionate (Flovent)

Combination ICSs and Long-Acting Beta2 Agonists Fluticasone and salmeterol (Advair) Budesonide and formoterol (Symbicort)

Control of asthma Administered on a fixed schedule Takes 2-8 days to see an effect, maximum benefit in 4-6 weeks

Adverse Effects Oropharyngeal candidiasis—rinse mouth after use Minimal adrenal suppression and bone loss Slows growth but does not reduce adult height Slight increased risk of cataracts, glaucoma, and osteoporosis

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ANTI-INFLAMMATORY DRUGS FOR ASTHMA LEUKOTRIENE MODIFIERS Prototype: Montelukast (Singulair)

Mechanism of Action

Uses Control of asthma (not used as first-line therapy) Prevention of exercise-induced bronchospasm Allergic rhinitis Not used for rescue

Other Leukotriene Modifiers Zileuton (Zyflo)—associated with rare liver injury Zafirlukast (Accolate)—associated with rare liver injury Fold here

Blocks leukotriene receptors Reduces inflammation, bronchoconstriction, and edema Decreases secretion of mucus Reduces eosinophils and other inflammatory cells Reduces dosage of inhaled corticosteroids

Adverse Effects GI upset Delayed effect Possible rare neuropsychiatric effects (mood changes, suicidal thoughts) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 75 Drugs for Asthma

ANTI-INFLAMMATORY DRUGS FOR ASTHMA LEUKOTRIENE MODIFIERS Prototype: Montelukast (Singulair)

ANTI-INFLAMMATORY DRUGS FOR ASTHMA Prototype: Cromolyn (Intal)

Mechanism of Action Suppresses inflammation, prevents release of histamine Stabilizes mast cell membrane Not a bronchodilator

Ch 75 Drugs for Asthma

ANTI-INFLAMMATORY DRUGS FOR ASTHMA Prototype: Cromolyn (Intal)

Uses Fold here

Control of asthma Must be given on a fixed schedule (not used for rescue) Prevents exercise-induced bronchospasm Allergic rhinitis (intranasal cromolyn)

Adverse Effects Safest of all antiasthma medications Rarely, can cause cough or bronchospasm

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BRONCHODILATORS BETA2-ADRENERGIC AGONISTS (Inhaled Short-Acting Agents)

Prototype: Albuterol (Proventil, Ventolin, Accuneb)

Prototype: Albuterol (Proventil, Ventolin, Accuneb)

Uses Rapid relief of asthma symptoms

Other Beta2-Adrenergic Agonist Levalbuterol (Xopenex, Xopenex HFA) Fold here

Mechanism of Action Activation of beta2-adrenergic receptors in the lung Promotes bronchodilation Rapid onset of action for rescue breathing Suppresses histamine release in the lung Increases ciliary motility

Oral Beta2-Adrenergic Agonists Albuterol (generic) tablets or syrup Albuterol (VoSpire ER) Terbutaline (Brethine) (Inhaled beta2 agents are preferred)

Adverse Effects Tachycardia, angina, and tremor

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 75 Drugs for Asthma

BRONCHODILATORS BETA2-ADRENERGIC AGONISTS (Inhaled Short-Acting Agents)

BRONCHODILATORS BETA2-ADRENERGIC AGONISTS (Inhaled Long-Acting Agents)

Prototype: Salmeterol (Serevent)

Prototype: Salmeterol (Serevent)

Mechanism of Action

Uses

Other Long-Acting Inhaled Beta2-Adrenergic Agonists Fold here

Activates beta2-adrenergic receptors in the lung Promotes bronchodilation Suppresses histamine release in the lung Increases ciliary motility

Ch 75 Drugs for Asthma

BRONCHODILATORS BETA2-ADRENERGIC AGONISTS (Inhaled Long-Acting Agents)

Formoterol (Foradil) Arformoterol (Brovana)

Asthma Should not be used alone Should be used in conjunction with an ICS

Adverse Effects Effect is delayed by 20 to 30 minutes Not to be used for rescue breathing Tachycardia, angina, tremor, and leg cramps Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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BRONCHODILATORS METHYLXANTHINES Prototype: Theophylline

Mechanism of Action

Other Methylxanthines

Produces bronchodilation by relaxing bronchi

Adverse Effects Narrow therapeutic range (5-15 mcg/mL) Dysrhythmias, ventricular fibrillation Convulsions, cardiorespiratory collapse, and death Many drug-drug reactions

Aminophylline

Fold here

Uses Asthma (Beta2 agonists and inhaled corticosteroids preferred)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 75 Drugs for Asthma

BRONCHODILATORS METHYLXANTHINES Prototype: Theophylline

INTRANASAL GLUCOCORTICOIDS (ICSs) Prototype: Fluticasone (Flonase)

Mechanism of Action

Other Intranasal Glucocorticoids

Anti-inflammatory actions suppress symptoms of allergic rhinitis Prevent or suppress congestion, rhinorrhea, sneezing, nasal itching

Uses Seasonal and perennial rhinitis Fold here

Adverse Effects Drying of the nasal mucosa, burning or itching Sore throat, epistaxis (nose bleed), and headache

Beclomethasone (Beconase AQ) Budesonide (Rhinocort Aqua) Flunisolide (Nasarel) Mometasone (Nasonex) Triamcinolone (Nasacort AQ)

Other Drugs Used for Allergic Rhinitis Oral and nasal antihistamines Intranasal cromolyn sodium (NasalCrom) Topical sympathomimetics (Oxymetazoline-Afrin) Oral sympathomimetics (phenylephrine, pseudoephedrine) Ipratropium bromide (Atrovent) nasal spray Montelukast (Singulair)

Ch 76 Drugs for Allergic Rhinitis, Cough, and Colds

INTRANASAL GLUCOCORTICOIDS (ICSs) Prototype: Fluticasone (Flonase)

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ANTITUSSIVES Prototype: Dextromethorphan

Nonopioid Antitussive

Nonopioid Antitussive

Mechanism of Action

Other Nonopioid Antitussives

Acts in the CNS to suppress cough Elevates the cough threshold

Adverse Effects Mild inebriation and mind-body dissociation when abused Can increase analgesic response to morphine

Fold here

Uses Acute cough

Diphenhydramine (Benadryl) Benzonatate (Tessalon)

Opioid Antitussives Codeine Hydrocodone

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 76 Drugs for Allergic Rhinitis, Cough, and Colds

ANTITUSSIVES Prototype: Dextromethorphan

HISTAMINE2-RECEPTOR ANTAGONIST Prototype: Cimetidine (Tagamet)

Mechanism of Action

Other Histamine2-Receptor Antagonists

Blocks H2 receptors on parietal cells of the stomach Reduces volume of gastric juice and hydrogen ion content

Fold here

Uses Gastric and duodenal ulcers Gastroesophageal reflux disease (GERD) Treatment of Zollinger-Ellison syndrome Aspiration pneumonitis Heartburn, acid indigestion, and sour stomach

Ranitidine (Zantac) Famotidine (Pepcid) Nizatidine (Axid)

Ch 77 Drugs for Peptic Ulcer Disease

HISTAMINE2-RECEPTOR ANTAGONIST Prototype: Cimetidine (Tagamet)

Adverse Effects Significant side effects are uncommon Antiandrogenic effects Confusion, hallucinations, CNS depression or excitation Pneumonia

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PROTON PUMP INHIBITORS (PPIs) Prototype: Omeprazole (Prilosec)

Mechanism of Action Inhibits the enzyme that generates acid production

Other PPIs

Adverse Effects Headache, diarrhea, nausea, and vomiting Gastric cancer, and hip fractures

Lansoprazole (Prevacid) Rabeprazole (Aciphex) Pantoprazole (Protonix) Esomeprazole (Nexium) Fold here

Uses Duodenal and gastric ulcers, erosive esophagitis GERD, dyspepsia Zollinger-Ellison syndrome

Other Antiulcer Drugs Sucralfate (Carafate) Misoprostol (Cytotec) Antacids

Combination Drugs for Helicobacter pylori–associated ulcers Helidac Pylera Prevpac

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 77 Drugs for Peptic Ulcer Disease

PROTON PUMP INHIBITORS (PPIs) Prototype: Omeprazole (Prilosec)

ANTIEMETIC DRUGS Serotonin-Receptor Antagonists

Prototype: Ondansetron (Zofran)

Prototype: Ondansetron (Zofran)

Mechanism of Action Suppresses emesis by blocking 5-HT3 receptors in the chemoreceptor trigger zone (CTZ)

Other Serotonin-Receptor Antagonists

Fold here

Uses Reduces nausea and vomiting caused by chemotherapy, radiation therapy, and anesthesia (postoperatively)

Adverse Effects Headache, diarrhea, and dizziness

Granisetron (Kytril) Dolasetron (Anzemet) Palonosetron (Aloxi)

Other Agents Used for Nausea

Ch 79 Other Gastrointestinal Drugs

ANTIEMETIC DRUGS Serotonin-Receptor Antagonists

Glucocorticoids Aprepitant (Emend) Benzodiazepines

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ANTIEMETIC DRUGS Dopamine Antagonists

Prototype: Prochlorperazine (Compazine)

Prototype: Prochlorperazine (Compazine)

Mechanism of Action

Other Dopamine Antagonists

Suppresses emesis by blocking dopamine2 receptors in the CTZ

Adverse Effects Extrapyramidal reactions, anticholinergic effects Hypotension and sedation

Fold here

Uses Nausea and vomiting Used after surgery, cancer chemotherapy, or other conditions

Phenothiazines Chlorpromazine (Thorazine) Perphenazine (Trilafon) Promethazine (Phenergan) Butyrophenones Haloperidol (Haldol) Droperidol (Inapsine) Metoclopramide (Reglan) Cannabinoids Dronabinol (Marinol) Nabilone (Cesamet) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 79 Other Gastrointestinal Drugs

ANTIEMETIC DRUGS Dopamine Antagonists

PROKINETIC AGENTS Prototype: Metoclopramide (Reglan)

Mechanism of Action Suppresses emesis by blocking receptors for dopamine and serotonin in the chemoreceptor trigger (CTZ) Increases upper GI motility by enhancing the actions of acetylcholine

Uses Fold here

Suppresses postoperative nausea and vomiting Suppresses emesis associated with chemotherapy, radiation therapy, toxins and opioids Relieves diabetic gastroparesis Suppresses gastroesophageal reflux disease (GERD)

Ch 79 Other Gastrointestinal Drugs

PROKINETIC AGENTS Prototype: Metoclopramide (Reglan)

Adverse Effects Sedation and diarrhea Extrapyramidal reactions, especially in children

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HYDROXYZINE (VISTARIL, ATARAX) Antiemetic Drug

Anticholinergic-Antihistamine

Anticholinergic-Antihistamine

Mechanism of Action Blocks histaminergic and cholinergic receptors

Adverse Effects Sedation, blurry vision, urinary retention, dry mouth

Fold here

Uses Nausea

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 79 Other Gastrointestinal Drugs

HYDROXYZINE (VISTARIL, ATARAX) Antiemetic Drug

PENICILLINS (PCNs) Narrow-Spectrum Penicillin (Penicillinase Sensitive)

Beta-Lactam Antibiotic

Beta-Lactam Antibiotic

Prototype: Benzylpenicillin (Penicillin G)

Prototype: Benzylpenicillin (Penicillin G)

Mechanism of Action

Parenteral PCN G (three salts)

Disruption of the bacterial cell wall Fold here

Uses Parenteral antibiotic treats gram-positive and gram-negative Streptococcus and Neisseria organisms, anaerobes, and others Drug of choice for syphilis

(1) Potassium PCN G (IM or IV) (2) Procaine PCN G (never used IV) (3) Benzathine PCN G (never used IV) Prescribed in units (1 unit = 0.6 mg)

Oral PCN

Adverse Effects Allergic reaction, pain at site of injection Neurotoxicities Do not mix PCN with aminoglycosides in IV solutions

Penicillin V (Veetids)

Ch 83 Drugs That Weaken the Bacterial Cell Wall I

PENICILLINS (PCNs) Narrow-Spectrum Penicillin (Penicillinase Sensitive)

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ANTISTAPHYLOCCAL PENICILLINS Penicillinase-Resistant Penicillins

(PCNs that cannot be inactivated by bacterial beta-lactamases)

(PCNs that cannot be inactivated by bacterial beta-lactamases)

Prototype: Nafcillin (Unipen)

Prototype: Nafcillin (Unipen)

Mechanism of Action

Other Antistaphyloccal Penicillins

Disruption of the bacterial cell wall Fold here

Uses Treats infections caused by penicillinase-producing strains of Staphylococcus (ie, S. aureus, S. epidermidis)

Oxacillin Dicloxacillin Methicillin (no longer available)

Adverse Effects Allergic reaction, GI effects Thrombophlebitis, hypokalemia

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 83 Drugs That Weaken the Bacterial Cell Wall I

ANTISTAPHYLOCCAL PENICILLINS Penicillinase-Resistant Penicillins

AMINOPENICILLINS Broad-Spectrum Antibiotics

Prototype: Amoxicillin

Prototype: Amoxicillin

Mechanism of Action Disruption of the bacterial cell wall

Other Aminopenicillins Ampicillin (Amoxicillin is preferred for oral therapy) Fold here

Uses Same antimicrobial spectrum as PCN plus increased activity against gram-negative bacilli Treats infections caused by Haemophilus influenzae, Escherichia coli, and Salmonella and Shigella organisms Ineffective against Staphylococcus aureus Adverse Effects Diarrhea

Ch 83 Drugs That Weaken the Bacterial Cell Wall I

AMINOPENICILLINS Broad-Spectrum Antibiotics

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ANTIPSEUDOMONIAL PENICILLINS Extended-Spectrum Penicillins

Prototypes: Ticarcillin, Piperacillin

Prototypes: Ticarcillin, Piperacillin

Mechanism of Action

Antipseudomonal Penicillins with Beta-Lactamase Inhibitors

Disruption of the bacterial cell wall

Fold here

Uses Antimicrobial spectra same as for aminopenicillins plus Pseudomonas aeruginosa, Bacteroides fragilis, and Enterobacter, Proteus, and Klebsiella spp. Used with aminoglycosides (not in the same IV) Can be destroyed by bacterial penicillinases

Ticarcillin with clavulanic acid (Timentin) Piperacillin with tazobactam (Zosyn)

Adverse Effects Sodium overload Interference with platelet function, leading to increased bleeding time

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 83 Drugs That Weaken the Bacterial Cell Wall I

ANTIPSEUDOMONIAL PENICILLINS Extended-Spectrum Penicillins

FIRST-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

Prototype: Cephalexin (Keflex)

Prototype: Cephalexin (Keflex)

Mechanism of Action Weakens the bacterial cell wall

Other First-Generation Cephalosporins

Adverse Effects Allergic reaction Pain at injection site Thrombophlebitis Rare antibiotic-associated pseudomembranous colitis (AAPMC)

Cefadroxil (Duricef) Cefazolin (IV) Fold here

Uses Gram-positive infections Surgical prophylaxis

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

FIRST-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

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SECOND-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

Prototype: Cefprozil (Cefzil)

Prototype: Cefprozil (Cefzil)

Mechanism of Action

Other Second-Generation Cephalosporins

Disruption of the bacterial cell wall

Fold here

Uses Enhanced activity against gram-negative bacteria Upper respiratory tract infections Acute otitis media (AOM) and sinusitis

Cefaclor (Ceclor) Cefotetan (Cefotan) Cefoxitin (Mefoxin) Cefuroxime (Ceftin) Zinacef

Adverse Effects Allergic reaction Bleeding tendencies (cefotetan) Thrombophlebitis Rare antibiotic-associated pseudomembranous colitis (AAPMC)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

SECOND-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

THIRD-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

Prototype: Ceftriaxone (Rocephin)

Prototype: Ceftriaxone (Rocephin)

Mechanism of Action Disruption of the bacterial cell wall

Other Third-Generation Antibiotics

Uses Active against gram-negative organisms Able to penetrate cerebrospinal fluid (CSF) Treats meningitis caused by gram-negative and gram-positive bacteria Effective for Neisseria gonorrhoeae infection

Cefdinir (Omnicef) Cefditoren (Spectracef) Cefixime (Suprax) Cefpodoxime (Vantin) Ceftibuten (Cedax)

Oral Fold here

IM, IV

Adverse Effects Allergic reaction Thrombophlebitis Rare antibiotic-associated pseudomembranous colitis (AAPMC) Fatal precipitate forms with calcium (Do not mix with Ringer’s lactate)

Cefoperazone (Cefobid) Cefotaxime (Claforan) Ceftazidime (Fortaz) [for Pseudomonas aeruginosa] Ceftizoxime (Cefizox)

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

THIRD-GENERATION CEPHALOSPORINS Beta-Lactam Antibiotics

Fourth-Generation Cephalosporin Cefepime (Maxipime) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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CARBAPENEMS Broad-Spectrum Beta-Lactam Antibiotics

Prototype: Imipenem (Primaxin)

Prototype: Imipenem (Primaxin)

Mechanism of Action

Other Carbapenems

Disruption of the bacterial cell wall

Adverse Effects GI effects Hypersensitivity reactions Suprainfections Seizures (rare)

Fold here

Uses Active against gram-positive cocci, gram-negative cocci, gram-negative bacilli, and anaerobic bacteria

Meropenem (Merrem IV) Ertapenem (Invanz) Doripenem (Doribax)

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

CARBAPENEMS Broad-Spectrum Beta-Lactam Antibiotics

VANCOMYCIN (VANCOCIN) Antibiotic

Mechanism of Action Inhibits bacterial cell wall synthesis

Uses

Fold here

Active against gram-positive bacteria Effective for serious infections, such as methicillin-resistant Staphylococcus aureus (MRSA) Second choice to treat antibiotic-associated pseudomembranous colitis Oral form used in patients who do not respond to metronidazole to delay resistance Used for patients allergic to penicillin

Adverse Effects Ototoxicity Rapid infusion can lead to red man syndrome (ie, flushing, tachycardia, and hypotension) Thrombophlebitis Immune-mediated thrombocytopenia

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

VANCOMYCIN (VANCOCIN) Antibiotic

NOTE: Infuse over 60 minutes or longer Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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TETRACYCLINES Broad-Spectrum Antibiotics

Mechanism of Action

Prototype: Doxycycline (Vibramycin)

Suppresses bacterial growth by inhibiting protein synthesis Binds to 30S ribosomal subunit to prevent the addition of amino acids Bacteriostatic

Other Tetracyclines

Uses Fold here

Rocky Mountain spotted fever, typhus fever, Q fever Infections caused by Chlamydia trachomatis Brucellosis, cholera Pneumonia caused by Mycoplasma pneumoniae Lyme disease, anthrax Gastric infections with Helicobacter pylori (peptic ulcer disease [PUD]) Periodontal disease and acne Community-acquired methicillin-resistant S. aureus (CA-MRSA)

Tetracycline (Sumycin) Minocycline (Minocin) Demeclocycline (Declomycin)

Adverse Effects GI irritation, suprainfection (AAPMC) Overgrowth with fungi (Candida albicans) Discoloration of teeth (avoid in children ,8 years old) Do not give to pregnant women Hepatotoxicity, exacerbation of renal impairment Photosensitivity, vestibular toxicity Chelating agents interfere with absorption Do not administer with: milk products, calcium, iron, magnesium, and laxatives

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 84 Drugs That Weaken the Bacterial Cell Wall II

TETRACYCLINES Broad-Spectrum Antibiotics Prototype: Doxycycline (Vibramycin)

MACROLIDES Broad-Spectrum Antibiotic

Prototype: Erythromycin

Prototype: Erythromycin

Mechanism of Action Inhibits bacterial cell wall synthesis Binds to the 50S ribosomal subunit to block addition of amino acids

Other Macrolides

Fold here

Uses Active against most gram-positive and some gram-negative organisms Treats atypicals such as: Pneumonia caused by Legionella pneumophila and Mycoplasma pneumoniae Bordetella pertussis, Corynebacterium diphtheria Can be used as an alternative to PCN in allergic individuals Treats chlamydial infections (urethritis, cervicitis)

Clarithromycin (Biaxin) Azithromycin (Zithromax) Dirithromycin (Dynabac) Troleandomycin (Tao)

Ch 85 Bacteriostatic Inhibitors of Protein Synthesis

MACROLIDES Broad-Spectrum Antibiotic

Adverse Effects GI effects, liver injury Inhibitor of cytochrome P450 Increases levels of theophylline, carbamazepine, and some statins QT prolongation and sudden cardiac death

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CLINDAMYCIN (CLEOCIN) Antibiotic

Mechanism of Action Inhibits bacterial protein synthesis Uses

Adverse Effects Antibiotic-associated pseudomembranous colitis (AAPMC) Diarrhea

Fold here

Used as an alternative to penicillin for serious gram-positive anaerobic infections Bacteroides fragilis, Fusobacterium sp., Clostridium perfringens

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 85 Bacteriostatic Inhibitors of Protein Synthesis

CLINDAMYCIN (CLEOCIN) Antibiotic

LINEZOLID (ZYVOX) Oxazolidinones Antibiotic

Mechanism of Action Bacteriostatic inhibitor of protein synthesis Binds to the 23S portion of the 50S ribosomal subunit

Fold here

Uses Active against aerobic and gram-positive bacteria Enterococcus faecium (vancomycin sensitive and vancomycin resistant) Staphylococcus aureus (methicillin-sensitive and methicillin-resistant strains) Staphylococcus epidermidis (methicillin-resistant strains) Streptococcus pneumoniae (PCN sensitive and PCN resistant) Adverse Effects GI effects Myelosuppression (reversible) Neuropathy HTN (blocks MAO)

Ch 85 Bacteriostatic Inhibitors of Protein Synthesis

LINEZOLID (ZYVOX) Oxazolidinones Antibiotic

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AMINOGLYCOSIDES Narrow-Spectrum Antibiotics

Prototype: Gentamicin

Prototype: Gentamicin

Mechanism of Action

Other Aminoglycosides

Disrupts bacterial protein synthesis Binds to the 30S ribosomal subunit Fold here

Uses Effective against aerobic gram-negative bacilli Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa

Tobramycin Amikacin (Amikin)

Adverse Effects Nephrotoxicity (renal dosing required to avoid toxic drug levels) Ototoxicity (requires peak and trough level monitoring) Intensifies neuromuscular blockade, leading to respiratory arrest Incompatible with PCN

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Ch 86 Aminoglycosides: Bactericidal Inhibitors of Protein Synthesis

AMINOGLYCOSIDES Narrow-Spectrum Antibiotics

SULFONAMIDES AND TRIMETHROPRIM Prototype: Trimethoprim/Sulfamethoxazole (Bactrim, Septra)

Mechanism of Action Combination antibiotic that inhibits bacterial synthesis of folic acid Uses

Adverse Effects GI effects Hypersensitivity reactions (Stevens-Johnson syndrome) Not for use in patients with sulfa allergies Hematologic effects: Agranulocytosis, leukopenia, thrombocytopenia, aplastic anemia Hemolytic anemia in patients with G6PD deficiency Kernicterus (do not use in infants ,2 months or pregnant women near term) Crystalluria, leading to renal damage (increase fluids) CNS effects, hyperkalemia, photosensitivity Increases the effects of sulfonylurea, leading to hypoglycemia

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Urinary tract infections Pneumocystis pneumonia (PCP) caused by Pneumocystis jiroveci

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FLUOROQUINOLONES Prototype: Ciprofloxacin (Cipro)

Mechanism of Action Inhibits bacterial DNA and cell division

Other Fluoroquinolones

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Adverse Effects Achilles tendon rupture and tendinitis (black box warning) GI upset CNS effects (dizziness, headache, and restlessness) Do not take with milk products or iron Elevates levels of warfarin Not recommended for children under age 18 Avoid in pregnancy

Respiratory fluoroquinolones: Moxifloxacin (Avelox)* and Levofloxacin (Levaquin) Gemifloxacin (Factive)* *Prolongs

QT interval

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Ch 90 Miscellaneous Antibacterial Drugs

FLUOROQUINOLONES Prototype: Ciprofloxacin (Cipro)

Uses Infections of the urinary, respiratory, and GI tracts, bones, joints, skin, and soft tissues Anthrax

Ch 87 Sulfonamides and Trimethoprim

SULFONAMIDES AND TRIMETHROPRIM Prototype: Trimethoprim/Sulfamethoxazole (Bactrim, Septra)

METRONIDAZOLE (FLAGYL) Antibacterial Drug

Mechanism of Action Causes cell death by damaging bacterial DNA

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Uses Protozoal infections Infections caused by obligate anaerobic bacteria (Bacteroides fragilis) Infections of the CNS, abdominal organs, bones, joints, skin, and soft tissue Infections of the genitourinary tract (Trichomonas vaginalis) Drug of choice for antibiotic-associated colitis caused by Clostridium difficile Eradicates Helicobacter pylori Used as prophylaxis in colorectal or abdominal surgery Adverse Effects Nausea, headache, dry mouth, metallic taste Vertigo, numbness in the extremities Dark discoloration of urine Disulfiram-like effect (vomiting) when used with alcohol Increases warfarin levels

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ANTIFUNGAL AGENTS Prototype: Itraconazole (Sporanox)

Mechanism of Action Causes bacterial cell wall to leak

Other Azole Antifungals

Uses Systemic and superficial mycoses (fungi) Fold here

Fluconazole (Diflucan) Voriconazole (Vfend) Ketoconazole (Nizoral) Posaconazole (Noxafil) Miconazole (Monistat) Clotrimazole

Other Antifungal Drugs Amphotericin B (causes nephrotoxicity) Caspofungin (Cancidas) Micafungin (Mycamine) Anidulafungin (Eraxis) Flucytosine (Ancibon) Nystatin (Mycostatin) Terbinafine (Lamisil) Butenafine (Lotrimin) Ciclopirox (Loprox, Penlac Nail Lacquer) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 91 Antifungal Agents

ANTIFUNGAL AGENTS Prototype: Itraconazole (Sporanox)

Adverse Effects GI effects, headache, abdominal pain, and edema Cardiac suppression Liver injury Inhibits hepatic drug-metabolizing enzymes Drug reactions with digoxin, warfarin, sulfonylureas, statins, proton pump inhibitors (PPIs)

Ch 90 Miscellaneous Antibacterial Drugs

METRONIDAZOLE (FLAGYL) Antibacterial Drug

ANTIFUNGAL AGENT Griseofulvin

Mechanism of Action Inhibits fungal mitosis Uses

Adverse Effects

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Superficial mycoses (fungi) Dermatophytic infections of the skin, hair, and nails Not active against Candida species or systemic mycoses May take 3 to 8 weeks to have an effect

Ch 91 Antifungal Agents

ANTIFUNGAL AGENT Griseofulvin

May diminish effects of warfarin

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ANTIVIRAL DRUGS Prototype: Acyclovir (Zovirax)

Mechanism of Action Suppresses synthesis of viral DNA

Other, Similar Agents

Adverse Effects IV administration can lead to phlebitis and nephrotoxicity Infuse slowly over 1 hour and maintain hydration Oral therapy may lead to nausea, vomiting, diarrhea Headache and vertigo

Valacyclovir (Valtrex) Famciclovir (Famvir)

Topical Agents Fold here

Uses Herpes simplex genitalis Mucocutaneous herpes simplex infections Varicella-zoster infections

Penciclovir (Denavir) Docosanol (Abbreva)

Ocular Agents Trifluridine (Viroptic) Vidarabine ointment (Vira-A)

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Ch 92 Antiviral Agents I

ANTIVIRAL DRUGS Prototype: Acyclovir (Zovirax)

DRUGS FOR HEPATITIS Prototype: Interferon Alpha

Mechanism of Action Decreases viral replication

Uses Hepatitis B and hepatitis C Fold here

Adverse Effects Flulike syndrome Neuropsychiatric effects—depression and suicidal ideation Fatigue, thyroid dysfunction, heart damage Bone marrow suppression

Ch 92 Antiviral Agents I

DRUGS FOR HEPATITIS Prototype: Interferon Alpha

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DRUGS FOR HEPATITIS Prototype: Ribavirin (Rebetol, Copegus)

Mechanism of Action Unclear Uses Used with interferon for treatment of hepatitis C Fold here

Adverse Effects Hemolytic anemia Fetal harm (FDA Pregnancy Risk Category X) Use a second reliable form of birth control during treatment and for 6 months after treatment

Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

Ch 92 Antiviral Agents I

DRUGS FOR HEPATITIS Prototype: Ribavirin (Rebetol, Copegus)

NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) Antiretroviral Drugs

Prototype: Zidovudine (Retrovir)

Prototype: Zidovudine (Retrovir)

Mechanism of Action

Other NRTIs and Combinations

Suppress the synthesis of viral DNA by blocking transcriptase Penetrates the CNS better than most antiretrovirals Fold here

Uses HIV infection

Adverse Effects Anemia and neutropenia from bone marrow suppression Lactic acidosis with hepatomegaly and hepatic steatosis Gastrointestinal effects CNS reactions (headache, insomnia, confusion, anxiety, and seizures) Myopathy

Ch 93 Antiviral Agents II

NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIs) Antiretroviral Drugs

Didanosine (Videx) Stavudine (Zerit) Lamivudine (Epivir) Abacavir (Ziagen) Tenofovir disoproxil fumarate (Viread) Emtricitabine (Emtriva) Zalcitabine (Hivid) Abacavir/zidovudine/lamivudine (Trizivir) Abacavir/lamivudine (Epzicom) Emtricitabine/tenovir (Truvada) Lamivudine/zidovudine (Combivir) Emtricitabine/tenofovir/efavirenz (Atripla) Copyright © 2010 by Saunders, an imprint of Elsevier Inc.

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NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Antiretroviral Drugs

Prototype: Efavirenz (Sustiva)

Prototype: Efavirenz (Sustiva)

Mechanism of Action Binds directly to HIV reverse transcriptase Inhibits reverse transcriptase

Other NNRTIs Fold here

Uses HIV infection

Nevirapine (Viramune) Delavirdine (Rescriptor) Etravirine (Intelence)

Adverse Effects CNS symptoms Rash, Stevens-Johnson syndrome Fetal harm Liver damage Many drug-drug reactions

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Ch 93 Antiviral Agents II

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIs) Antiretroviral Drugs

PROTEASE INHIBITORS Antiretroviral Drugs

Prototype: Ritonavir (Norvir)

Prototype: Ritonavir (Norvir)

Mechanism of Action Inhibits the enzyme protease, which HIV requires to mature

Other Protease Inhibitors

Adverse Effects Hyperglycemia/diabetes, fat maldistribution, hyperlipidemia Increased bleeding in hemophiliac patients Reduced bone mineral density Elevation of serum transaminases Can increase or decrease levels of other drugs Many drug-drug interactions

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Uses HIV infection

Lopinavir/ritonavir (Kaletra) Indinavir (Crixivan) Saquinavir (Invirase) Nelfinavir (Viracept) Amprenavir (Agnerease) Fosamprenavir (Lexiva) Atazanavir (Reyataz) Tipranavir (Aptivus) Darunavir/ritonavir (Prezista)

Ch 93 Antiviral Agents II

PROTEASE INHIBITORS Antiretroviral Drugs

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INTEGRASE INHIBITORS Antiretroviral Drugs

Prototype: Raltegravir (Isentress)

Prototype: Raltegravir (Isentress)

Mechanism of Action

Other Drugs for HIV

Inhibits integrase to stop HIV replication

Adverse Effects Diarrhea, nausea, fatigue, headache, and itching Possible myopathy and rhabdomyolysis

HIV Fusion Inhibitor Fold here

Uses HIV infection

Enfuvirtide (Fuzeon)

Chemokine Receptor CCR5 Antagonist Maraviroc (Selzentry)

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Ch 93 Antiviral Agents II

INTEGRASE INHIBITORS Antiretroviral Drugs

Dietary Supplement Ginkgo biloba Glucosamine Green tea

Saw palmetto

Soy St. John’s wort

Valerian root

Potential Problems

Improves age-related memory Osteoarthritis Improves mental clarity, weight loss, cancer prevention Anxiety Stimulant Irritable bowel syndrome, antibiotic-associated diarrhea Benign prostatic hypertrophy

May suppress coagulation Increased risk of bleeding Increased heart rate, hepatotoxicity Reduces effects of warfarin Hepatotoxicity, sedation Stroke, MI, and death Flatulence

Prevention of cancer Menopausal symptoms Mild to moderate depression

Sedative, promotes sleep

Suppresses platelet aggregation-risk of bleeding Fetal harm in women Increased risk of oxalate Kidney stones Photosensitivity Accelerates metabolism of many drugs Serotonin syndrome Drowsiness

Dietary Supplement

Uses

Potential Problems

Black cohosh

Menopausal symptoms

Coenzyme Q-10

Echinacea Feverfew

May reduce myalgias associated with statins Prevents bacteria from adhering to urinary tract Stimulates immune system Migraine prophylaxis

Flaxseed

Dyslipidemia and constipation

Garlic

Dyslipidemia and hypertension

Ginger root

Vertigo, nausea, and vomiting Anti-inflammatory effects

Liver toxicity Comes mixed with St. John’s wort; many drug-drug reactions May antagonize the effects of warfarin GI upset and formation of uric acid kidney stones Allergic reactions Suppresses platelet aggregation-risk of bleeding Suppresses platelet aggregation-risk of bleeding Suppresses platelet aggregation-risk of bleeding Suppresses platelet aggregation-risk of bleeding High doses can cause spontaneous abortion

Cranberry juice

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Kava Ma huang Probiotics

Uses

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Ch 107 Dietary Supplements

Commonly Used Dietary Supplements

Commonly Used Dietary Supplements

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