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Coronary Artery Di sease

6

Coronary Artery Diseases Types of angina I

IStable angina l !unstable angina ll Exercise-induced Prinzmetal angina

Chronic angina l

~octumal Anginal

Or Vasospastic angin Coronary artery Diseases The most common complications associated with Coronary artery disease include: Angina pectoris, Myocardial infarction, post Myocardial infarction,and Ischemic stroke. Insufficient supp ly of oxygen to heart can lead to Ischemic conditions. Myocardial ischem ia is usually caused by coronary vessel atheroscleros is (High LDL and high cholesterol is the most common risk facto r). As the vessel lumen nalTOws blood flow is reduced. •

Other causes that limit coronary blood How include: Arterial thrombi and Spasm

A ngina Pectoris Angina are those symptoms of myocardial ischem ia that occur when myocardial oxygen availability is insufficient to meet myocardial oxygen demand. These symptoms include: Chest discomfort often described as heaviness, pressure, and squeezing. The sensation is localized typically in the sternal region. •

Symptoms often last one to five minutes. Angina can radiate to the left shoulder, to both anns (ulnar surfaces of the foreann and hand), and can radiate to the neck,jaw, teeth, epigastrium and back.

Types of angina Angina Pectoris

Severe chest pain because of inadequate coronary blood How to supply oxygen demand. Which is usually aggravated by exertion or stress and relieved by nitroglycerine. The most common form of IHD.

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www. PhannacyPrep.Com Types of angina pectoris

Nocturnal angina (angina decubitus)

Stable anginal Classic angina (most common-90%) Unstable angina Exercise induced angina Exertion angina Chronic angina Prinzmetal angina octurnal angina Mostly secondary to atherosclerosis (high LDL) Due to obstruction in coronary arteries More predictable Precipitated by exertion or emotional stress or by heavy meal. Relieved by rest or using nitroglycerine's The most serious one (worsening pain) Thrombosis in a branch Caused by formation atherosclerotic (disease of arteries, in fatty plaques develop in inner wall), occurs at rest ACE inhibitors are used as single treatment Decreased response to rest and nitroglycerine This angina occurs in the recumbent position and is not specifically related to either rest or exertion Nitroglycerine may relieve the paroxysmal nocturnal dyspnea

Prinzmetal angina (vasospastic or variant angina)

Coronary artery spasm that reduces blood flow precipitates this angina. Secondary to coronary artery spasm Usually occurs at rest (pain may disrupt sleep) Calcium channel blockers are most effective

Stable angina or classical

Unstable angina/resting! Crescendo

I

I Vasod ilators I INitrates I

I

I

Drugs Used In Angina Pectoris

I Cardiac depressants I

Calcium blockers, and ACE inhibitors Nifedipine, Verapamil, Diltiazem

Short duration Inhaled amyl nitrite Sublingual Nitroglycerine Isosorbide dinitrite

I

Intennediate Oral regular or sustainedrelease Nitroglycerine lsosorbide dinitrite

I

~-blockers

Proponolol

I

Long duration Transdermal Ntiroglycerine patch

Treatment of angina The following beta-blockers are used in treatment of angina: Beta-blockers with Selective Intrins ic Sympathomimetic Activity (ISA) : Acebutolol hydrochloride Beta-blockers with Non-I SA: Atenolol and Metoprolol tartrate can be used. Beta-blockers w ith Nonselective, ISA: Pindolol Beta-blockers with Nonselective, Non-ISA: Nadolol, Propranolol hydrochloride, Timolol maleate Calcium Channel Blockers are used in treatment of angina: Amlodipine besylate, Diltiazem hydrochloride, Nifedipine, Verapamil hydrochloride The following Coronary Vasodilators, Nitrates are used in treatment of angina: Copyright C 2000-2009 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without pemlission. This manual is being used during review sessions conducted by PhannacyPrep.

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Coronary Artery Disease

Nitroglycerin, Isosorbide dinitrate, Isosorbide·5· mononilrate.

Nitrates

Ht

Nitri tes

rl t

Nitric oxide (NO)

1-+1t cGMP ~

V",So<

Ca2+ channel Blockers These agents are used to treat hypertension and are effective in treating angina as wel l. All musc les, including the smooth muscle of the blood vessels, require calcium in order to contract. If the Copyright 0 2000·2009 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without pennission. This manual is being used during review sessions conducted by PhannacyPrep.

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calcium-channel blocking agents block the entrance of calcium into the muscle, the muscle will not contract. This will allow themuscle to relax and subsequently reduce the blood pressure. Other therapeutic uses: angina, migraine, antiarrhythmic.

Non dihydropyridines

Diltiazem hydrochloride Verapamil hydrochloride

Verapamil is similar to Beta blockers in effect Verapamil can cause bradycardia The effect on Heart is graded from higher to lower: verapamil > diltiazem > nifedipine Verapamil ~ avoid using in CHF (cause -ve inotropic effect) and constipation Nifedipine Dihydropyridine Felodipine Amlodipine Nicardipine Nifedipine is similar to Nitrate in effect (peripheral ~ decrease aftcrload, dihydropyridine can cause tachycardia. Dihydropyridines Relax and dilating arteries . The effect on vascular smooth muscles is high with dihydropyridine: nifedipine > diltiazem > verapamil Comparison of d ihydropyridine and Non-dihydropyridine Mechanism

DHP

NDHP

Cause Reflex tachycardia No heart blockade Peripheral vasodilation Amlodipine long half-life (Only amlodipine does not cause reflex tachycardia) Can be used in asthma Avoid CYP3A4 Inhibitorsflnducers

Cause Bradycardia Cause Heart blockade Myocardial vasodilation Negative (-ve) inotropic effect (worsening CHF)

iltiazem

Coronary Dilatation ~

(GFJ)

Side effects: flushing, profound low blood pressure, swelling oflegs and feet, constipation and stomach upset. Ifedema (swelling) of the legs and feet occur, a diuretic may be added to the regimen.

Nifedipine (Adalat) Mechanism Therapeutic use

Side Effects

A calcium blocker which interfere with conduction of signals in the muscles of the heart and vessels. Given regularly to prevent Angina attacks. Reduce high blood pressure and is often helpful in improving circulation to the limbs in disorders such as Raynaud's disease. Blood pressure will fall too low' and sometimes causes heart rhythm. Tachycardia, flushing, headache, dizziness, Orthostatic hypotension, and edema

Amlodipine (Norvasc) Mechanism

A calcium blocker which interfere with conduction of signals in the muscles of the heart and vessels. Copyright 0 2000-2009 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without pennission. This manual is being used during review sessions conducted by PharmacyPrep.

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www.Pharmacv Prep.Com Therapeutic use

Sidc Effects

Coronary Artery Disease Angina and Chest pain Can be safely used by asthmatic and non·insulin·dependent diabetic. Blood pressure may fa ll too low Sometime may cause mild to moderate leg and ankle swelling

Diltiazem (Cardizem) Mechanism Therapeutic use Side Effects

A calcium channel blocker that interfere with the conduction of signals in the muscles of the heart and blood vessels. Angina Longer acting formulations are used to treal hi gh blood pressure Usually well tolerated, occasional hypotension or orthostatic hypotension, flUSh ing, arrhythmia, and bradycardia. Use with caution in patient with CHF

Myocardial Infarction (Heart attack) Mechanism Drug of Choice for Acute coronary syndrome

ASA

Post MI

Myocardial ischemi a is usually caused by coronary vessel atherosclerosis . As the vessel lumen narrows blood flow is reduced Acute MI 7 ~· b l ockers, ACE, CCB, Prophylaxis (prevention)7 ASA (60·8\ mg/day), Ni troglycerine Severe chest pain-7 Morphine Anticoagulants-7 Heparins. LMWH, Warfarin Antipiatelets7Aspirin, clopidogrel, • M9i01en~ tlc\opldme ~Iood A = AnalgesIcs .IIU A = AntipyretIcs Anglo1enslnl A = Antiinflammatory ~An9~'ln • conwrtlng A = Anllplatelets (60·81 mg/day) Kidney fn>yMe lung Aspi rin decrease morbidity and mortality AngIoIensltl ll

fj-"" "'- t

oCCB

ft

Vasocon.-"

tAldost_ _ 1on Thrombolytic used for coronary t ADH $«Ietlon perfusion, eg: streptok inase l·ThI." Also Glycoprotein lIB, lilA inhibitors such Ttrofiban can be used

STEMl treatment ASA, Beta·blockers, Nitrates, CCB, Thrombolytics NSTEM I treatment: ASA, Beta·blockers, Nitrates, Heparin

Coronary Artery Disease Ti.ps -I, () 1:> ~'M

I

Nitroglycerine spray storage and admin istration 7 'y-~~ "0.- • Nitroglycerine SL storage condition require-7 c..-...J.- l '('~ ~ C' Light sensitive -7 ~~ Nitrates should be avoid taking with -7 .1. " What is active moiety of nitrates 7 ~ \. \..) \ ( ~~():-­ . Nitroglycerine is chemically classified as -7 l\J 1 ~ Nitroglycerine + seldanafil can cause hypotens ion and this due to nitroglycerine and seldanafil.

i:.. e-..p

i

:::--r )

!J ~

\r

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The most common side effect ofni lroglycerine is headache; therefore nitroglycerine should be taken while sitting position . Nitroglycerine patch can cause tolerance, to avoid tolerance use nitrate free period. What drugs effective in MI prevention and treatIl}ent -7 "t.,~). .f\ ') J What drugs should be avoided in MI -7 ~\ ?\~u..\.\IJ ~ c ~_ 1'1 _ I M Severe C.hest pain associated with Ml treatedb~ -7 \'\};~ ~ 0 0 ~ -

-r\ ()

H, -) -:;.

M,

STEM] -) ~ ;":-'-~ ~ NSTEMl -) ,,",0'" S.. ~ MAt what dose ASA act as Antiplatelet -7 b C> _ {1 \) , ASA act as irreversible Antiplatelet drug Nitrates -7 Increase nitrites -7 Increase N itric oxide (NO) -7 vascular smooth muscle relaxation

Abbrevation and Tenninology LDL IHD SL CN CCB MI ACE ASA STEM ] NSTEMI

Low-density Lipoprotein

Angiotensin-Converting Enzvme Acetyl Saliaylate ST-Segment Elevation Ml non-ST-Se ment Elevation MI

Generic and Brand Verdanafil Sildenafil Tadanafil Nitro russide

Levitra Viagra Cialis Nitrooress

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Congesti ve Heart Failure

7

Congestive Heart Failure (CH F) Drugs Used to treat Congestive Heart Failure

I

I

Positive inotropic drugs

I

I

Vasodilators

I

I Cardioic g1ycosides Digoxin Digitoxin Quabain

p-agonists, Dobutamine POE inhibitors Amrinone

ACE inhibitors Captopril Enalapril Lisinopril

Nitrates, Nitroprusside, Hydralazine, POE inhibitors Milrinone

Congestive heart failure is characterized by reduced cardiac output so that the heart is not able to pum p sufficient oxygenated blood strongly enough to reach the tissues. The heart beat is weak and rapid and the heart muscles may hypertrophy (grow larger) to compensate for reduced cardiac output. Atrial fibrillation occurs when the atria beat rapidly and out of sequence. Cardiac Heart failure due to: Increased sympathetic activity Fluid retention (edema) Decrease in heart muscle contractil ity Due to negative (-ve) inotropic effect Due to +ve chronotropic effects Left systolic dysfunction Left sided failure (systolic failure) This is the most common type of heart failure, Often due to hypertension. Due left ventricular (systolic) dysfunction leads to pulmonary edema; Symptoms: SOB (Dyspnea), Wheezing. Can be treated by ACE l, and beta blockers (rarely in chronic), only carvedilol (PI , P2 and 0.1). The Most common etiology of left sided heart failu re is: Due to impaired pumping abi lity of the heart Usually occurs in Left ventricular ejection fraction May be present without CHF Ejection fraction is lower than 35%, it is Left ventricular dysfunction (systolic failure) Right Sided Heart failure (diastolic failure) Due to chronic lung d isease, Diastolic filling is impaired this can leads to peripheral edema. Symptoms: edema in veins, legs, bowel. Diuretics or Dihydropyridine cess treats ri ght-sided heart failure. Ejection fraction is greater than 45%, it is Right ventricular dysfunction (Diastolic fa ilure)

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The Treatment of Congestive Heart Failure (CHF) The treatment of congestive heart failure may include: diurectics to reduce the back-up of fluids in the lungs an the rest of the body; vasodilators that decrease vacular resistance and help improve circulation through the heart; ACE inhibitors to improve cardiac function an y may slow the progression ofCHF and Angiotensin n ATI receptor antagonists.

Cardiac glycosides Mechanism

Positive Inotropic effect

Negative chronotropic effect

Digoxin, digitoxin, Ouaban Cardiac glycoside increase myocardial contractility ad efficiency Improve systemic circulations Improve renal perfusion Reduce edema Inhibit the membrane bound Na+lK+ activated ATPase Increase intracellular sodium concentration Reduce calcium transport form cell Facilitate calcium entry via voltage gated membrane channel Increased vagal tone of the (SA) node Reduced CNS sympathetic out flow Systemic arteriolar and venous constriction

Vagomimetic effect

Increased vagal tone of the sinoatrial (SA) node.

Side effects

Early stages of toxicity: GI: Anorexia, nausea & vomiting and diarrhea eNS: Headache, visual disturbances (green and yellow vision) Confusion, neuralgia, delirium

Digoxin (Lanoxin) Digoxin

Bioavailability

Therapeutic use

Digoxin is the most widely used cardiac g lycoside Don' t confuse with digoxin with doxepin, Desoxyn, or digitoxin. 75% bioavailability, 20-40%, protein bound T 1!2=40 hr Urinazy excretion CHF. Atrial fibrillation, protects ventricles

Inh ibits (slows)

+-r.~9i\""'a/K ATPase

+---;:=:f;-Na

Reduced Na gradient ~)OW~ Caremoval

Digoxin Mechlln l~m of Action

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Congestive Heart Failure I" sign: 01 effects: Nausea, vomiting, diarrhea, Blurry yellow vision, scotoma. CVS ~ Arrhythmias, ventricular tachycardia CNS ~ visual disturbances (blurred vision) Patient should understand the importance offollow up laboratory test for this medication; Pulse

Monitor

Increased force of contractio n

Decreases and systolic volume

Decreases wa ll tension

ECG Counselling

• • • •

Increased ejection of blood

Adjust the dose with renal failure patients Do not take extra dose if dose missed. Use same brand consistently. Avoid high dose sod ium medications Do not take with high fiber food ; fiber diet may reduce digoxin absorption.

Improves Oxygenation

Digoxin mechanism of action Electrolyte 'rearrangement' (Mechanism)

j lnotropy (Desired)

Tachyarrhythrnias (S ide effect)

Increased Vagal tone (Mechanism)

Bradyarrhythmias

(Side effecl)

! Heart Rate (Desired)

Digitalis toxicity Digitalis toxicity

Predisposing factors

Toxicities of digoxin increased by renal failure (decrease excretion) Hypokalemia, or hyperkalemia (potentiates drug effect) Hypothyroidism, hypoxia, renal failure and myocarditis also predisposing factors for digitalis toxicities.

Drugs that cause digitali s toxicity Drugs that 1 digoxin levels Amidome Verapamil Erythromycin TetracycJin I Quinidine

Drugs that ! K+ levels Thiazides Loop diuretics Corticosteroids

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www.PhannacvPrep.Com Digital is toxicity: Reduced potassium levels Digitalis toxicity can be managed by: discontinue digoxin, monitor blood potassium levels. Sever tachycardia may require the use ofFAS antibodies. Which bind to inactive digoxin Di gifab

Digital is toxicity Management

Antidote

P,_L P

Comparison of digoxin and digitoxin Digox.in Digox.in has advantage of a relatively short half· life, which allows better treatment of toxic reactions.

Di itoxin Binds strongly to proteins extravascular space, resulting in large volume of distribution.

Rapid onset of act ion.

Slow onset of action

Digoxin eliminated largely unchanged in Urine

Extensively metabolized by liver before it excrete in feces.

_u - N,

Left ventricular heart failure cause -7 -_----~ -::---0 (2, Ri ght ventricular heart failure cause -7 ..£I~-..Q ~. DOC fo rCHF 7 1\L C) . '", ;\.~ -\I ~L Digoxin pharmacological action include -7 -tV v l...~, ~ . ~ Comparison of digoxi'l. and ii,gitoxin, which is short acting and why-7 ~(j 2000·2009 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without permission. This manual is being used during review sessions conducted by PhannacyPrep.

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Antiarrhythmic Drugs

8

Anti Arrhythmic Drugs Antiarrhythmic Drugs Classification

T Class II P-blockers Esmolol (Propranolol) TImolol Atenolol Metoprolol Nadolol

Class I la-Na! channel blockers Quinidine Procainamide DisoQY!iIll ide \.;.\miodaronO Ib: Lidocaine Mcxilctinc Tocainide Ic: Flecainide ropafenone la

Ib Ie II III

IV

Class III K+ channel

inhibitors Amiodarone (Cordarone) Bretylium Dofetilide Sotolol

N a+ channel blocker N a+ channel blocker N a+ channel blocker Beta blockers K+ channel blockers Cal+ channel

Class rv Ca 1+ channel blockers Verapamil Diltiazem Nifedipine (procardia, Adalat)

Miscellaneous Adenosine Magnesium

Slows ohase 0 deoolarization Shortens nhase 3 renolarization Sil!nificantlv slow nhase 0 denolarization Decrease Dhase 4 denolarization Prolon!! nhase 3 renolarization Shortens action notential

Arrhythmias Arrhythmias develop because of abnormal impulse generation, propagation or both. Cardiac arrhythmias are related to abnormal electrical activity within the heart resulting in either altered rhythm or impulse conduction. Dysrhythmia--disturbed heart rhythm Arrhythmia - absence of rhythm Bradycardia - a heart rate that is lower than nonnal «60 beats/min). Tachycardia - a heart rate that is higher than normal (> 100 beats/min). Paroxysmal - an arrhythmia that suddenly begins and ends (may occur with fever) Sinus bradycardia - low sinus rate I OO/min; usually due to abnormal focus within the atria and paroxysmal in nature. This type of rhythm includes paroxysmal atrial tachycardia (PAT). Atrial fibrillation - uncoordinated atrial depolarizations. Junctional escape rhythm - SA node suppression can result in AV node-generated rhythm of 4060 beats/min (not preceded by p-wave). AV nodal blocks - a conduction block within the AV node (or occasionally in the bundle of Hi s) Copyright 10 20(}()+2009 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without permission. This manual is being used during review sessions conducted by PharmacyPrep.

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Antiarrhythmic Drugs

[hal impairs impulse conduction from the atria to the ventricl es . Types of pacemakers • Natural (main) pacemaker of heart SA node • Latent pacemaker of heart AV node Bundles of His Purkinje fibers Pulse direction: SA node ? AV node ? His ? Purkinje fibers Supraventricular arrhythmias (SVA)-arrhythmias develops above the bundles of Hi s Ventricular arrhythmias (VA)-->devel ops below the bundle of Hi s Types of arrhythmias Supraventricular (atrial) SVA Premature atrial contraction Atrial flutter Atrial fibri llation Paroxysmal supraventricular tachycardia (PSVT) Si nus tachycardia Si nus bradycardia Ventricular arrhythmias (VA) Premature Ventricular Contraction (PVC) Ventricular tachycardia (VT) Ventricular fibrillati on (VF)

• Heart blockade: The el ectrical impulses are partially or fully blocked between the atria and the ventricles . The SA node in the right atrium ' fires' at the normal rate, but the rate at which the ventricles contract (pulse rate) depends on how many impulses get through to the ventricl es. Three types: 1it degree ---blockage of pulsation 2nd degree ----blockage of pulsation 3rd degree---complete heart block First-degree heart block means there is a slight delay in each impulse going from the atria to the ventricles. But, each impulse does get through and the heart rate is nonnal. Second-degree heart block means that some impulses from the atria are not conducted through to the ventricles. The rate that the ventricles contract can then be slow. Third degree or ' complete heart block' means that no impulses are conducted through. The ventricles then comract at their own intrinsic rate of about 20-40 beats per minute. So, you have a very slow pulse. Myocard ial Action Potential Curve Myocardial action potential curve reflects action potential, which describe electrical activity of five phases. This occurs in atrial and ventricular myocytes and Purkinje fibers

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Antiarrhythmic Drugs

Phase 0: Rapid Depolarization: Na+ enters the cell -7All Class la drugs Phase J: Early rapid repolarization: K~ leaves the cell Phase 2: Plateau: Ca2+ enters the cell Phase 3: Final rapid repolarization: K+ pumped out of the cell Phase 4: Slow depolarization: K* inside the cell and Na+, Ca2+ out side the cell Phase I to starting phase 3 is Absolute refractor Period or Effecti ve refractory period -7 The cell cannot respond to any stimuli During Phase 3 is relative refractory period -7 The cell ability to respond stimuli increases or cell can respond to strong sti muli

2

mV 3

IJ,,~

"

~ '-.

~----~=~~-~~~~ Myocardial action pOlential curve

Torsade de pointes A problem in one of the ion channels can prolong the Q-T interval. A prolonged Q-T interval can increase ri sk for a type of arrhythmia called torsade de pointes. When torsade de pointes occurs, heart cannot pump enough oxygen-rich blood to the rest of body, especially your brain. Torsade de pointes can also lead to ventricular fibrillation, a dangerous fonn of arrhythmia that causes rapid, uncoordinated contractions in the muscle fibers of the ventricles. With ventricular fibrillation, the heart cannot pump oxygen-rich blood to the rest of the body, wh ich can lead to death. Drugs and diseases that can lead to QT-prolongation Phenothiazines and haloperidol -7 anti psychotics Type III antiarrhythmic drugs In patients with hepatic fai lure. Electrocardiograph Wave Forms The electrical acti vity occurred during depolarization and repolarization transmitted through electrodes attached to the body and transformed by an electrocardiograph (ECG) in to series ofwavefonns; P WAVE: indicated atrial depolarization PR INTERVAL : indicates the spread of the impulse from the atria through Purkenje fibres. QRS complex: indicates ventricular depolarization ST segment: indicates phase 2 or the action potential- the absolute refractory period. T wave: shows phase 3 of the action potential-ventricular repolarization. Q-T interval -7 mechani cal contraction of the ventricles (Torse de pointes) U wave -7 caused by hypokalem ia

,

•

Arrhythmias Treatment Class I Class la

Quinidine -7 decrease 50% digoxin, SE:Torsades de pointes Procai namide -7 SE:Torsades de pointes Di sopyramide -7 SE:Torsades de pointes

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Therapeutic use Class Ib

Therapeutic use Class Ic

Therapeutic use Class II Beta blockers

Therapeutic use Class III K ~ channel blockers

Class IV Ca2+ channel blockers Therapeutic use Digoxin

Therapeutic use

Antiarrhythmic Drugs

Pharmacological action; Slow the phase 0 (slow entry of Sodium ion) Prolong re-polarization Prolong effective refractory period Indicated to treat SVT, VT Lidocaine Tocainamide Mexiletine Pharmacological action: Min imal effect on Phase 0 Slow phase -III repolarization (decrease K pump o ut) Indicated to treat VT, VA iv Lidocaine: used to treat cardioversion related arrhythm ias Encainide, Propafenone ~ decrease 25-50% digoxin Flecainide Pharmacological action: Very effective on slowing phase 0 depolarization Little effect on repoiarization Indicated to treat VA Propranolol Atenolol Timolol Pharmacological action: Competitively block catecholamine induced stimulation of Beta receptor thereby Suppress phase I V depolarization Indicated to treat AT, SVT, VT, VA Amiodarone ~ blue skin, photosensitivity, photophobia Bretyl ium Sotalol Prolong Phase II I repolarization (Prolong QT interval) ~ Torose de pointes Indicated to treat VA Verapamil Diltiazem Nifedipine Pharmacological action: Shortens action potential Indicated to treat SVA, VA Pharmacological aClion: Effects vagotonic response (vegomimetic) thereby increases AV nodal refractoriness. It is contraindicated in ventricular fibrillation. Ventricular taChycardia may result from digitalis toxicities Indicated to treat SVA (atrial arrhythmias) only Contraindicated in ventricular arrhythmias

Quinidine (Quinaglute) Mechanism

Binds to sodium activated channels Inhibits ectopic arrhythmias, VA

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www.PharmacyPrepCom Therapeutic use Drug-Drug interaction

Side Effects

Counselling

Antiarrhythmic Drugs Atrial, AV junctional, and ventricular tachycardia. Maintain sinus rhythm after direct atrial flutter or fibrillation. Antihypertensive, Anticoagulant - Quinidine may increase the effects of these drugs. Phenobarbital and Phenytoin - reduce the effect of quinidine Digoxin-Quinidine increases the effects of digoxin (decrease 50% digoxin dose). SA and AV block or asystole, nausea, vomiting, diarrhea (cinchonism-large doses-blurred vision, tinnitus, headache, disorientation and psychosis. Torsos De pointes (VA) • Toxic level ~induce ventricular tachycardia. • Increases steady state concentration of digoxin by displacing PPB • Report tinnitus, blurred vision immediately • Avoid concurrent use of aluminum containing antacids • Keep out of reach of children • Administer after meal to minimize gastric distress • Don ' t crush tablets because drug irritates mucosa.

Procainamide (Pronestyl) Mechanism Side Effects

Binds to sodium activated channels Chronic use: lupus like syndrome (25-30%), toxic levels-asystole or induction of VA. GI intolerance is less than quinidine. CNS· depression, hallucinations and psychosis.

Amiodarone (Cordarone)

Side effects (4P)

Amiodarone is structurally related to thyroxine, and it contains iodine. I. DOC antiarrhythmic & recommended in more severe LVD & ifC! with I BB 2. IV Amiodarone --effec-tive in terminating VT, more so in preventing recurrence 3. Most effective fo r thx in electrical storm 4. Usually used as an empiric therapy ,f.) Respiratory: Pulmonary, mcluding Intererstitia~leumonitis; Respiratory muscle impairment GI: nausea, anorexia, constipation; hepatitis and cirrhosis; Hypothyroidism ; hyperthyroidism; Amiodarone inhibit(fripheral conversion

ofT~ toT]

Counseling

~

Blue skin color gn:aentation), corneal deposits, hepatic toxicity, optic neuritis, erectile dysfunc IOn~otophobia Avoid exposure to sunlight, use sunscreen Avoid grapefruit juice

Digoxin (Lanoxin) Therapeutic use Contraind icated

Atrial arrhythmias Ventricular fibrillation and hypokalimic patients

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Antiarrhythmic Drugs May be taken with or without food Meals wI bran fiber, antacids may reduce amt of drug absorbed Store between15-25 0 C in a tight container and protect from light

Antiarrhythmic drugs Tips What phases of action potential curve have no effect of stimuli 7 ~e. \ ~ Relative refractory period is 7 ~ _ . Phase I action potential is 40 (+ve) due to 7 '-("~ ~ L. 0.. f'I_ What drug cause QT prolongation (torse des pointes) 7 . Y~Il'J·~:;·I({ ~ . Digoxin is contraindicated in what type of arrhthmias 7 V.a......., . F \ b Patient taking digoxin, the prescription is expired what will you do? ~ K Amiodorone side effects are: Photosensitive reactions, skin pigmentation, Blurred vision. Pulmonary toxicity, Pneumonitis.

t;

p

'(',,~

'A,

Abbrevation and Tenninology SVA PSVT VA VT SVT

Supra Ventricular Arihythmias Paroxysmal SupraVentricular Tachycard ia Ventricular Arihvthmias Ventricular Tachvcardic SUDraventricular tachycardia

SA

AV PVC ECG PPB LVD BS

Premature ventricular contraction Electrocardiograph Beta Blocker

Generic and Brand Amiodarone Digoxin Procainamide Diso ramide Encainide Ro afenone Digoxina I Quinidi ne Procainamide Flecainide

Cordarone Lanoxin Procaine SR No aceCR Enkaid Rhythmol Lanoxin uinagiute, Quinidex Pronestvl Procan Procanbid Tambocor

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Antiarrhythmic Drugs

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W:iJ~R,1L ~ \90.] ~~ IS due negative calcIUm balance Side effects Increase risk of infection due to impaired wound healing and immunosuppression associated with Diabetes -7 due to hyperglycemia SE oral steroids Increased appetite can cause we ight gain Hypertensi on is due to increase water retention (Edema) Peptic ulcers Euphoria Psychosis Immunosuppression -7 due to suppression ofh!:E.

Adrenocorticoids Tips Increase in cortisone cause --> Decrease corticosteroids Gause~> What is steroid sparing drug --> Aldosterone are secreted from -->

Abbrevation and Tenninology eNS

Centa[ Nervous S stem Intra Ocular Pressure

lOP

Generic and Brand Cortisone Hydrocortisone Betamethasone Beclomethasone Prednisolone Prednisone Triamcilone M ethvTrll-edn iso lone Ketoconazole Snironolactone Mife ristone Me ra ne AminO-;;-' utethi m ide

Cortone A-hvdroCort, Ala-Cort, Ala-Scalpt, Anu-Med HC Oi rosone. Oi rolene Beclovent Beconase A Beconase. var Vancenase AX-Pred Bubbli-Pred Econo red Econo red Plus Oeltasone. Predone. Stera red Stera red OS A-Methanred Cortimed De medalone De o-Medrol Medralone Extina Kuric Nizoral Shamnoo Nizoral Nizoral A-D Xolepel Aldactone Snirono Mife rex Meto irone Amino lutethimide

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Oral Contraceptives

27

Oral Contraceptives Oral contraceptives (birth control pills) are combinations of estrogen and progestins. The combination preparations may be monophasic, biphasic or triphasic. They contain various estrogens and progestins . Some common ones are listed: Drugs that Causes Of OC Failure

Contraindications

Precautions

Starting Hormonal Contraceptives

Alcohol ·excessive chronic, Anti biotics (ampicillin, cotrimoxazole, griseofulvin, metronidazole, nitrofurantoin, neomycin, penicillin, rifabutin, rifampin & tetracycline), Anticonvulsants (carbamazepine, ethosuxim ide, oxcarbazepine, phenobarbital, phenytoin, primidone & topiramate l dose), Antivirals (nelfinavir & ritonavir), modafinil, red clover & St. John's wort. Active thromboembolic disease ·-undiagnosed vaginal bleeding Acute or chronic obstructive liver disease Known or suspected breast cancer Known Or suspected pregnancy Hypertension· may use OCs if hypertension controlled CVD, hyperlipidemia· OCs with new progestins preferred because of more favorable lipid profile Diabetes -low dose OCs unlikely to affect glucose control but estrogen may complicate vascu lar disease Epilepsy - some anticonvulsants ! oes efficacy due to l metabolism; may require use ofOCs with >35ug EE Hepatitis, cirrhosis - avoid OCs if active disease; may use if liver enzymes have returned to normal Gallbladder disease - iIlay be exact:rbatt:d by Des Migraine - avoid OCs if classic, complex, age ~35 (lstroke) Inflammatory bowel disease - active diarrhea may reduce absorption and efficacy of OCs and require backup method Systemic lupus erythematosus - avoid ~C 's as estrogens can complicate vascular disease Smoking women over age 35 - if light smoker «\5cigs/day) or on nicotine patch, can use 20 Jlg EE product but l risk ofDVT. Starting Combined Des: Most effective ifstarted Day I of menstrual period can be started any day up to Day 6 To avoid weekend periods, start on I S1 Sunday after period begins If started after Day 5 use backup method for first 7 -10 days as ovulation may not be suppressed Starting Progestin-only Pill (PO P): Start on Day 1 of menstrual period an~ daily thereafter Use backup method for first month

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www.PhannacvPreo.Com Starting Hormonal Contraceptives

Side Effects & Their Management

Miss pills

Plan B (Levonorgestrel O.7Smg per dose) Or Minipill Or Morning after pill or Emergency contraception Side effects plan B

Oral Contraceptives Starting Depo-Provera: im Should be inj ected during the first 5 days of menstrual cycle rule out pregnancy Repeat injection ql2 weeks - effective for up to 14 wks Breakthrough bleeding - most common in 1st 3 months; if persists beyond 3-6mon check for other causes (eg. chlamydia). Change to oe with 1 estrogen/progestin depending on when BTB occurs in the cycle; may also be related to poor compliance, smoking, DIs Breast tendemess - if persists beyond 1st 3months rule oul pathologic causes; change to oe with! estrogen/progestin Weight gain - may i appetite in 1st month but overall weight gain is minimal with low dose oes & within nonnal limits for age-related gain; may be cyclical due to Na & H20 retention Nausea - often subsides within 3 months; take at hs with food or change to lower estrogen content Headache - tension headaches unaffected but honnone related or vascular migraines may i!; if precipitated or exacerbated by oes should avoid their use Acne - sometimes worsens initially but usually improves in the long tenn; change to ! androgenic OC or use topical therapy Chloasma - irreversible and idiosyncratic; exacerbated by sunlight so use sunscreen and reduce exposure; ! estrogen dose Miss one pill: Take as soon as you remember and take usual pill next day. This means that you might take two pills in a day. Miss two pills in a row: First two weeks : Take two pills the day you remember and two pills next day. Then take one pill until you finish pack. Use back up method of birth control, if you have sex in next seven days of missing pill. Third week: Safely dispose remained pills and start new pack same day. (If you're on Sunday start schedule continue one pill until Sunday). You may not have periods this month. If you miss two periods in a row call doctor. Progestin only Very efective within 24hrs and can be used upto 5 days unprotected inter course. Schedule 2 (Phannacist intervention) Contains 2 pills (use 2nd pill after 12 hours of I " pill) To treat Nausea and vomiting associated with this pill can be treated by Gravol (dimenhydrinate) Nausea (23.1%), Vomiting (5%), Dizziness, fatigue

Abbrevation and Tenninology DC

DVT BTB

Oral Contraceptive Deep Veinthrombosis Break Through Bleeding

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Oral Contraceptives

Generic and Brand Levonorgestrel, Ethinyl Estradi ol Ethinvl Estradiol, Norethindrone

Alesse Brevicon Demulen Diane·35 Ortho· Cept Marvelon Ortho M in·Ovral Triphasil Svnphasic

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Oral Contraceptives

~

;;>

O--~

M'J~ ~ ~~ \-1et-~o tra~

~~ \v,1:)~ ~

4 'l.--65 years Degenerative joint disease caused by breakdown of the cartilage b/w bones, degradation of articular cartilage in ~ynov ialjoints

Rheumatoid Arthritis In the morning (last I hour) Not localized Worsens with prolong inacti vity. (Usually improves with activity). Common Autoimmune inflammatory condition Chronic systemic Symmetrical synovitis affecting similar joints bilateral.

Abbrevation and Tenninology I Cylco Oxygenase

Generic and Brand I Diclofenac

Cataflam, Solaraze

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Desease Modifying Antirheumatic Drugs

M~"'OL~() .. LC)

ll~ / --:-,

e Osteoporosis associated with the use of which of OA drug --> Which DMARDs require ophthalm ic examination monitoring- > Mucositis is side effect of 7 Pannus means7

Abbrevation and Tenninology DMARD RA

ASA TNF

LFT

esc uc

NSAID SJS

OA

Disease Modifying Antirheumatic Drugs Rheumathoid Arthritis Acet 1 Salia late Tumor necrosis factor Liver Funtion Test ComDlete Blood Count Ulceralive Colitis Nonsteroidal Anti-Inflammatory Drug Steven Johnson Syndrome Ostreoarth itis

Generic and Brand Arava Leflunomide Cyc1osporine Neoral Minocycline Cleeravue-M Dynacin Minocin Myrac 0 - enicillamine Cuprimine Infliximab Remicade Embrel EtanerceDt Anakinra Kineret Copynght (:I 2000-2009 1lP$ Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to reproduce without pennission. This manual is being used during review sessions conducted by PhannacyPrep.

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Gout and Hyperuricemia

~ 30 Gout and Hyper uricemia I

I Gout attack therapy

I

r

Hyperuricemia TheraDV

I

I

I

Antimitotics and anti-inflammatory action

Colchicine

I

Corticosteroids

I

Nonsteroidal Anti-inflammatory Drugs (NSA IDs)

UricosuricS71ncrease excretion of uric acid

Xanthine oxidase inhibitors " prevents conversion of purine to uric acid

Indomethacin 7 Highest anti· inflammatory NSAID Phenylbutazone Sulindac

Dexamethasone Dexamethasone sodium phosphate Hydrocortisone sodium succinate Methylprednisolone acetate Prednisone Triamcinolone

Probenecid" Take with full glass

H,O SuJfinpyrazone7 Take with full glass of HP

0

Allopurinol" Take with full glass of HP

Basics of Gout arthritis Gout is a d isease in which monosodium urate monohydrate (MSU) crystal deposit in joints, soft tissues such as cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium tubules. Gout arthritis involves 4 Stages Asymptomatic hyperuricemia Acute gouty attacks Intercritical gout Tophaceous gout Asymptomatic hyperuricemia Nonnal serum urate levels: Woman 360 mmollL Men 420 mmollL

r...........

lL

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~

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R~

..-.

J

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Gout and Hyperuricemia

Hereditary metabolic disease that is a fonn of acute arthritis and is marked by inflammation of the - Joints. Gout is associated with increased body stores of uric acid. Acute attacks involve joint inflammation caused by precipitation of uric acid crystals. Hyperuricemi a ~ Urate crystal in joints -? inflammatory response Acute gout arthritis Abrupt onset of excruciating pain and inflammation of joint during the night or early morning. Patient cannot tolerate even light pressure such as a bed sheet on the affected j oint. Attacks often resolve spontaneously over 3- 10 days. J.IIline treatment is N SAID's For sever pain a Intra-articular inj ection of corticosteroid. (especially in patient with polyarticular gout) Colchicinea It relieves pain withjn 24 hours in 90% patients if treated within few hours of attacks. Side effects: Gl ~ abdominal pain, cramps, diarrhea, N and V Rarely a Neuropathy, myopathy, bone marrow suppression Intercritical gout: Most patient have second attack within 6 - 24 months . Chronic tophaceous gout: May occur after 12 year of first attack.

Colchicine - "'> .v> J c::C>~ ~ t.-r \:,

3~ '~

Mechanism

Colchicine is as selective inhibitor of microtubule assembly, reduced leukocyte migration and phagocytosis: the drug may also reduce production ofleukotriene B4 • Because it reacts with tubulin and interferes with microtubu le assembly, this is general mitotic poison. Tubul in is necessary for nonnal cell division, motility and much other process: therefore, colchicine has systemic side effects if used in excess

Therapeutic use

Used only for GOUl, can be used as IV Antiinflammatory action only No analgesjc effect No J![jrp5uric effect

Side effects

Diarrhea, nausea, and abdominal pain . Chronic use can produce hemorrhagic gastroenteritis, hematuria, alopecia, agranulocytos is and peripheral neuropathy

Drug-Drug interactions

Taking cyclosporine with colchicine may lead to adverse effects on the kidneys.

Indomethacin (Indocin) Mechanism

Potent NSA1D's such as indomethac in also effective (but not as selective) in inhibiting the inflammation of acute gouty arthritis. NSA1 D's acts through prostaglandin formation and through inhibition of crystal phagocytosis by macrophage

Therapeutic use

Use to treat gout arthritis

Side effec ts

Indomethacin may cause renal damage or bone marrow depression .

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Gout and Hyperuricemia

Mechanism

Uric acid is both actively secreted and actively reabsorbed in the kidney. Probenecid partially inhibits both the active secretion and the active reabsorption. Uricosuric agents are weak acids that compete with uric acid, in the S2 segment of the proximal renal tubu le, for reabsorption by weak acid mechanism Gout Before using probenecid check to see that the patient is not a high excreter of uric acid, otherwise the use of drug may precipitate uric acid crystals in the kidney

Therapeutic use Side effects

Counselling Take plenty of water

Sulfinpyrazone (Anturane) Mechanism

Allopurinol (Zyloprim)

Metabolism Therapeutic use Side effects

C 1.< . ; : " , ,,

&" .~"'~ ~,

." , AZo " ,0 I'r """ --. """t ~ e.

Sulfinpyrazone partially inhibits both the active secretion and the active reabsorption Inhibits platelet aggregation Gout arthriti s Urate crystal formation Take plenty of water

Therapeutic use Side effects Counselling

Mechan ism

""'-,,-X'c"'-r-\.o~ ~~ 'r "';;4;' Y~

en ~

Rlbo," -

Allopurinol is a suicide inhibitor of xanthine oxidase (XO) Purine a uric acid Allopurinol aoxypurinol Reduce uric acid pool

r

P + ATP

s - Ph"pho"bo,yl - 1 - PY'TO'h'" (pRPp) + GI,"ml"

Inosinic Acid j

Hypersensitivity rashes Inosine Peripheral neuritis and necrotizing j 1 vasculitis Hyroxilnthinp GI intolerance, diarrhea Ir.X~M-'~h~I"-,-o-xo~·d-,,'eI In condition with large purine turnover xanthine Xanthine stone formation may occur Ir.X~M----'th~'"-,-o-xo~d-,,'eI Alkalinize the urine to increase solubi lity With 6~merca topurine (but not thioguanine) Uric Acid Must decrease by 2 I use Wit a opurm . Xanthine oxidase is main biotransforming enzyme for 6-mercaptopurine. Example of6-mercaptopurines is azathioprine, an anticancer drug Take plenty of water

! !

Counselling

Gout arthritis Practice Tips

T}>~"--.A a

~,}

t'"

Not. used in acute gout a~ack7A\ 0 - 1'\4. Punnestructurepresentm 7 ~\f,

l\~t,,,J:) ~po00 I 4

31 - 2

www.PharmacvPrep.Com Dose

Alendronate Counseling

Osteoporosis Alendronate (Fosamax) available in a once weekly 70mg tablet Available dosage forms: 5 mg, IOmg, 35 mg, 40 mg, 70 mg Prevention of osteoporosis in postmenopausal women - once 5 mg daily Treatment of osteoporosis in women 10 mg once daily or 70 mg tablet once weekJy Treatment and prevention of glucocorticoid induced osteoporosis in men and women- 5 mg once daily Treatment of osteoporosis in men one 10 mg tablet once daily or 70 mg once a week. Risedronate (Actonel) = Available dosage forms: 5 mg, 35 mg, Take first thing in the morning empty stomach Take with plenty of water Do not lie down for 30~45 min after medications (slay upright) Calcium supplements should be separated by 2hours before or after

Raloxifene (Evista) Mechanism

Selective Estrogen Receptor Modulator (SERM) Estrogen like action on bone and lipid metabolism Estrogen antagonist action in breast and endometrium

Therapeutic use

Prevents postmenopausal bone loss, increases bone density approximately 3%, decrease vertebral fractures Has estrogenic and antiestrogenic activity It does not have effect on endometrium like tamoxifen and estrogen, therefore may not predispose uterine cancer. Lower cholesterol and LDL but no effect on HDL and TG . For prevention of osteoporosis in postmenopausal

Side Effects

Increase risk of Deep vein thrombosis (DVT) Avoid in who are pregnant and planning to become pregnant. Aggravate hot flushes Coadministration of cholestyramine reduces absorption up to 60%. Do not take together.

Calcitonin salmon Calcitonin is a hormone secreted from thyroid gland Calcitonin hormone helps bone formation by transporting Ca from blood to bones Mechanism: Directly effect on osteoclast and decrease bone resorption through direct effect. Two products are available Miacalcin 200 JU/day intranasally Common SE is nasal irritation Calcimar, caltine 50 - 100 JU sc/day or Q 2,.j day or 5days/wk Not approved for osteoporosis

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Osteoporosis

Osteoporosis Tips

present~ 0 ~ ft- ~ _n

_r rO~4~ ~ Riskfactorsofosteoporosis~ ~ost_~ ~.- ~Ot>~_-' \_- ',t: ~e!~

Bone remodeling occurs, when whi lj;h.is Osteoporosis is caused by ~ Q... ~~ )

Androgendeficiencycause~ t\'1pDoc~~ d {~J~) ~ What is NOT risk factor ofosteroporosis ~ 0 ~ S ii:y Recommended daily allowance of vitamin D is 7 40 0 •

o....~

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Ff 0 I 4 Elderlymayabsorbcalciumpoorlydueto \~ ~ o....sease-7 D ~ -l

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Abbrevation and Tenninology Selective Estrogen Receptor Modulator Low Densitv Liooorotein Hi gh Densitv Liooorotein

SERM

LDL

HOL TO OVT

Deep Vein Thrombos is

Generic and Brand Raloxifene Alendronate Etidronate Risedronate Fosavance

s-J 1~ '" Ptr'-'"-~~ U,"\

t. O-t

I

:,nort actmg Albuterol (salbutamol) Isoproterenol Isoetharine Metaprotereno] T

Long acting Fonneterol Salmeterol

Asthma Triggers (factors that increase risk of asthma)

~Tj]jrigi9giOi.rs"---------------lN~,,\vvrtlt< ~ CO P D Early asthmatic response- Symptoms only (i.e., bronchoconstriction) Cold ai r Exercise Emotional stress Late asthmatic response- Worsening asth ma Allcrgens (Pollens. cockroach, molds, animal dandur) Respiratory viruses Occupational chemicals Drugs - ASA, NSAIDs Food additives - sulfites, tartrazine Air pollution (including cigarette smoke)

GERD Sinusitis

Treatment for chronic asthma

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Asthma and COPD

Beta? agonist drugs Be~Agonist

Short acting beta., agonist (SABA) Albuterol (S-albutamol) Terbutaline \,..,... 1. Metaproterenol ~.. \ ~ Co...~ Pirbuterol C ~ acting bet~ agonist (LABA)

~ ~~

c.....tto

~'--' Q(5

c::::::

-.

.

Salmeterol ""~ Fonnoterol (short ~ I- 3 min and long duration 12 hours)

Mechanism

Bronchodilation Vasodilatation Slightly decrease peripheral resistance Increase muscle and liver glycogenolysis Relax uterine muscles Increase release of glucagon

Therapeutic use

Treat Asthma

Short acting beta 2 agonist: Albuterol, terbutaline, pirbuterol

Rapid onset of action and provide relief for 4 to 6 hours. Indicated in symptomatic treatments, rescue agents, combat acute bronchoconstriction Albuterol, terbutaline, pirbuterol has little alpha-I and beta -I effects. Does not effect by COMT enzymes because these are acti vated by non COMT Inhalation route has less toxic side effects than systemic routes. Have less tachycardia, hyperglycemia, and hypokalemia effects with inhalations routes. Short acting are best reserved for treatment of acute exacerbations and prophylaxis o f exercise induce asthma (EIA)

Long acting bela 2 agonist: Salmeterol

Salmeterol has long duration of action, providing bronchodilation for at least 12 hours, and slow onset of action. Indicated in maintenance treatment in combination with corticosteroids especially for nocturnal asthma, EIA, and COPD Not indicated in acute asthmatic attacks

SE

Tremors (shaking) ~ due to effect on bet~ receptors of muscles Cardiovascular SE (tachycardia, palpitation) due to effect on Beta I receptors

Salbutamol (Ventolin) Mechanism

Sympathomimetic bronchodilator that relaxes the muscle surrounding the bronchioles

Therapeutic use

Relieve symptoms of Asthma, chronic bronchitis and emphysema.

Side effects

Fine tremor of the hands Anxiety, tension restlessness

Recommendation

Inhalation is considered more effective because drug is delivered directly to the bronchioles

Contraindication

Caution in diabetes, Hyperparathyroidism, CV disorders

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Asthma and COPD

Onset ofbronchodi lation

10-20 minutes

Duration of bronchodilation

4-5 hours

Salmeterol (Serevent) Mechanism

A Sympathomimetic Bronchodilator, And Relaxes The Muscle Surrounding The Airways In The Lungs But Because It Has A Slow Onset Of Effect, It Is Not Used For Immediate Relief Of Symptoms Of Asthma. It Has Longest Duration OfBronchodiiation

Therapeutic use

Indicated In COPD And Emphysema Prevention Of oClumal Asthma Prevention Of Exercise Induced Asthma

Side effects

Dry And Irritated Nose, Throat (Inhalations), Tremors, Nervousness, Cough Wheezing

Drug-drug intemclion

There is an increase risk of low blood potassium levels when high doses of salmeterol are taken with corticosteroids, Theophylline And Diuretics

Metaproterenol (Alupent) Mechanism

Produces dilatation of the bronchioles and improved airway funct ion

Therapeutic use

Asthma 5-10 Minutes

Onset of bronchodilation Duration of action

4-5 Hours

Terbutaline (Bricanyl) Mechanism

A sympathomimetic bronchodilator that dilates the small ain'lays of the lungs

Therapeutic use

Treatment and prevention of the bronchospasm occurring with asthma, chronic bronchitis, and emphysema Bronchodi lator and reduce uterine contractions in premature labor.

Side effects

Muscle tremor, especially of the hands Nervousness and restlessness

Drug-drug . interaction

Administered subcutaneously and orally. Terbutaline may intemct with MAOIs to cause a dangerous rise in blood pressure

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Asthma and COPD

Corticosteroids Corticosteroids

Mechanism

Therapeutic use

Side effects

Recommendation Combination products

Prednisone - PO, Prednisolone PO, Beclomethasone Budesonide Fluticasone Triamcilone Steroids have no effect on the airway smooth muscles; rather decrease the number and activity of cells involved in airway inflammation. (Macrophage, eosinophiis, and T-Iymphocytes). Prolonged use for several months reduces the hyperresponsiveness of smooth muscles. Antiinflammatory response reduced by reversal of mucosal edema Asthma Allergic rhinitis lnhaled glucocorticosteroid are the drug of choice in moderate to severe asthma that req uires bet~ agonist more than once daily. Inhaled corticosteroids are deposited in the airway and mouth Severe asthma systemic glucocorticoids (short time use only) Glucocorticoids most effe ctive when taken conti nuous Oral thrush (candidiasis): Can be reduced by rinsing mouth or using spacer Spacers: reduces systemic side effects and reduces thrush. Nasal sprays : systemic absorption is minimal and side effects are localized nasal irritation, nosebleed, sore throat, rarely cand idiasis To red uce corticoids side effects rinse and gargle mouth after inhalations. Adviar = Salmeterol (LABA) + Fluticasone (steroid) Symbicort = Formeterol (LABA) + Budesanoide

PrednisoneJPrednisolone (Inflamase) Mechanism Therapeutic use Side effects Drug-Drug interaction Recommendation

Predn isolone is the active form of Prednisone, is a powerful corticosteroid Skin diseases, rheumatic disorders, and certain blood disorders. Long term treatment with high doses can cause fl uid retention, indigestion, diabetes, hypertension and acne. It may increase the adverse effects of Diuretics Prolonged systemic use can lead to such adverse effects as diabetes, glaucoma, cataracts, and fragile bones, and may retard growth in children. Dosages are usually tailored to min imize these effects.

Fluticasone (Flovent) Mechani sm

A corticosteroid drug used to control inflam mation in asthma and allergic rhinitis.

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Asthma and COPD

Mechanism

It does not produce relief immediately, so it is important to take it regularly.

Therapeutic use

Prevent asthma attack (by inhaler) Prevent allergic rhinitis

Side effects

Fungal infection causing irritation of the mouth and throat (inhaled form) To minimize side effects thorough rinsing the mouth ang gargling with water after inhalation is recommended

Monitoring

Periodic checks of adrenal funct ions may be required if large doses are being taken.

Budesonide (Pulmicort, Rhinocort) Mechanism

A corticoisteroid in a form of slow release capsule that reduces inflammation of whether nose, lungs, or intestines

Therapeutic use

Prevent attacks of asthma but not stop an existing attack. Enema to treat ulcerative colitis Rel ieve symptoms ofCrohn's disease

Side effects

Fewer and less serious side effects

Drug-Drug interaction

Ketoconazole and other azole antifungals can increase the blood level of oral Budesonide.

Monitoring

When taking in a large dose, period ic checks may be needed to insure the adrenal glands are working properly Chi ldren inhalers may have their growth (height) monitored regularly.

Beclomethasone (Qvar) Mechanism

A corticosteroids that controls nasal symptoms by reducing inflammation and mucus production in the nose.

Therapeutic use

Relieve the symptoms of allergic rhinitis and to control asthma Helps to reduce symptoms such as wheezing and coughing Given to people whose asthma is not responding to bronchodi lators alone.

Side effects

Fungal infections causing irritation of the mouth and throat (inhalers)

Recommendation

Rinse mouth and gargle with water after each inhalation.

Monitoring

When large doses are being used, periodic checks is required to ensure that the adrenal glands are functioning healthy.

Anticholinergics Ipratropium Bromide

Atrovem

Mechanism

An anticholinergic bronchodi lator that relaxes the muscles surrounding the bronchioles. Has longer effect but slower onset.

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Asthma and COPD

www.PhannacyPrep.Com Therapeutic use

Maintenance treatment of reversible ainvay disorders, particularly Chronic Bronchitis Runny nose due to allergy (nasal spray) T he drug of cho ice for COPD

Side effects

Anticholinergic s ide effects Has rare side effects

Onset of effect

5·15 minutes

Duration of action

8 hours

Tiotropi um (Spiriva)

Long acting muscarinic blocker Administered by special devise handihaler Available as capsule

Combivent

Ipratropium bromide + Salbutamol (MO l) and Nebul izers

All MDI

Should shake before use

Leukotriene inhibitors Zafirlukast Mechanism

Leukotriene inhibitors Inhibitors ofLTC 4 and LTD4 receptors Steroid sparing properties

Therapeutic use

Have anti-inflammatory and bronchodilator activity Reduce bronchospasm and associated symptoms that are mediated through leukotrienes. Used fo r exercise induced asthma DOC for aspirin induced asthma

Side effects

Sudden withdrawal of corticosteroid patient taking Zafirlukast precipitated Churg·Strauss syndrome (Severe asthma with increase eosinophil count in blood). Vasculitis angiitis: A patchy inflammation of the walls of small blood vessels

Drug.Food interaction

Zafirlukast-Food reduces bioavailability take I hour before or 2 after meals Take empty stomach Oral tablets Used in 12 year or Over 12 year old only

Montelukast

Singulair Chewable tablets and G ranules

Mechanism

Inhibitors of LTC 4 and LTD4 receptors

Therapeutic use

Have antiinflammatory and bronchodilator activity Reduce bronchospasm and associated symptoms that are mediated through leukotrienes. Used in Exercise induced asthma

Side effects

Headache Nausea and diarrhea Abdominal pain

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Asthma and COPD

Drug-Food interaction

Montelukast may be taken without regard to food. Chewable tablet Powder Over 2 year old can be used

Theophylline and Aminophylline Mechanism

(A minophylline will breaks down to Theophylline in the body) Induce phosphodiesterase (POE) inhibition Alter intracellular calcium Adenosine antagonisms Increase circulating catecholamines

Therapeutic use

Antiinflammatory action Chronic asthma----mainly decreases symptoms Bronchitis and emphysema Use as a preventive measure, and is added to standard therapy

Side Effects

GI effects -7 Nausea, vomiting, abdominal cramps, Diarrhea, headache, CVS -7 Palpitation CNS effects -7 Insomnia, seizures, dizziness, nervousness, restlessness Overdose causes seizures, and arrhythmias. Dosage should be adjusted based on serum levels Sustain release theophyllines allow for a longer dosing interval and improve compliance. Compliance to oral theophylline also may better than that inhaled bronchodilators and corticosteroids Oral therapy: Sustained released theophylline allows for longer dosing interval and improve compliance

Recommendation

Monitoring

Factors that alter theophylline clearance

-.

Periodic checks on blood levels are requires especially the Serum level Theophyllines are contraindicated in patients with hypersensitivity to xanthine compounds. Cuation in patient with peptic ulcers and seizure diseases Increase theophylline clearance (decrease levels): age: 1-9 years, '::, High protein diet, smoking (tobacco, Qlarijuana), fever, drugs such as carbamazepine, Phenobarbital, phenytoin and nfampl~ . Decrease theophylline clearance (Increase levels): Age (elderly, infants, under 6 months age, premature neonates), CHF, Fatty food, High carbohydrated diet, Liver dysfunction and Drugs such as: Oral contraceptives, Non selective beta blockers, CCBs, Macrolide antibiotics, Clindamycin, Zafirlukast, Allopurinol.

~obllr1J

tartmmillipirle RrtamplCln

-

cyt:losporin

l'

Theophylline

ke:Dc~naztll ~,~

smoking

U phenytoin anbcoagulam

i

~~~nitidlne

ropilll'(Jloi

"

ftuconilzol obesity lmonary aedema

COf'

allopurinol uncosul'llic drugs Erylhromyt:in

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Asthma and COPD

Cromolyn and nedocromil Mechanism Therapeutic use

Side Effects

Mast cell inhibitors Has Anti-inflammatory Action Effective in prophylactic, has anti-inflammatory effect. Not used in acute asthmatic attacks Cromolyn administered by inhalation of micro fine powder or as an aerosol solution. Cromolyn poor absorption causes more side effect that can be reduced by powder or aerosol formulations . Internasal cromolyn reduces allergic rhinitis symptoms Bitter taste lrritation of nasal mucosa, pharynx, larynx

Chronic Obstructive Pulmonary Diseases (COPD) CO PD : Chronic Obstructive Pulmonary Di seases; COPD is due to chronic obstruction in airway passage. COPD is two types: • •

Emphysema (high altitude sickness) Chroni c bronchitis .

EMPHYSEMA is a disease in which the small air exchange sacs (alveoli) in the lungs become permanently enlarged and damaged (alveoli walls destroyed) decreas ing oxygen absorption and resulting in shortness of breathe. CHRONIC BRONCfITTIS is an inflammation of the airways in the lungs that causes your lungs to produce excessive amounts of mucus (phlegm). This reduces the flow of air to the lungs . Onset age 45 years Risk Factors that Cause COPD • Smoking (80·90%) • Family History • Occupational exposures to ceI1ain ducts and fumes • Air Pollution • Second Hand Smoke • Asthma Drug used for the treatment of CO PO

•

• Beta adrenergic agonists • COI1icosteroids • Ipratropium (Atrovent) Theophylline

Asthma and COPD Tips

PDt:. Theophylline inhibit activity of -7 Leukotrienes are chemical derivatives of -7

l

""L,, ll..,,,,,,boV, ~ OL str.,.Q,( ,is; leishmaniasis Availability: 3% cream/lotion/oral suspension Not absorbed in the G IT

Mechanism

Bind to ergosterol from pores resulting in the leakage of cell ular contents

Side effects

Infusion related fever and chills; anorexia; muscle pain; headache Non-infusion related: nephrotoxic, hyperkalemia, hypomagnesemia, tachycardia, anemia, thrombocytopenia, arrhythmias, YF, HTN, tachypnea, leukoencephalopathy, dry skin, skin discoloration, SJS, toxic epidermal necrolys is, agranulocytosis, jaundice, hemorrhage, sore throat

Contraindication

Allergies

WARN ING

Apply only to patients with progressive, potentially fatal infections and should not be used to treat non-serious infection Monitor Lab test sp. Renal function (frequently), liver function, serum electrolytes particularly magnesium and potassium, blood count, Hgb conc. Not use for dosage adj ustment Does not penetrate CSF

Drug interaction

Antineoplastic= increase renal toxicity, bronchospasm, hypotension Corticosteroids/ACTH= increase. amphotericin B-induced hypokalemia, renal toxicity; Nephrotoxic agents (Cisplatin, pentamidine, aminoglycoside, cyclosporine= increase renal toxicity Digitalis glycosides= Amphotericin B-induced hypokalemia, increase digitalis toxicity Skeletal muscle relaxants= enhance cureiform Others: AZT, chloramphenicol, antithyroid, colchicine, deferoxamine, streptozocin, plicamycin, lithium, penicillamine Overdose : cardiorespiratory arrest

Prccauti"on

Storage of dry powder; 2-8 deg, protect from light Give slow IV infusion

Counselling

When applying topicals on the skin, protect nails and clothes as it may stain

References

CPS 2004, 854-855, Comprehensive Pharmacy Review, 5th Ed. Page 795,

Nystatin Category Therapeutic use

Mechanism Side effects

Polyene antibiotic, structurally similar to Amphotericin B, fungicidal, fungistatic Active against Camlitia ~p. Primarily use as a topical agent in vaginal and oral candidiasis Not very effective against dermatophytes (Tinea) Inhibit growth of yeast, binds to sterol in the funga l cell membrane, increasing permeability and causing leakage of intracellular components Irritation e.g. mild digestive upset, Nausea & Vom iting diarrhea; creaml vaginal tablet- itching, burning, irritation

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Antifungals

Advantage Drug interaction

Can be use by pregnant women

Precaution

Application of vaginal tablet

Counselling

Nystatin liquid-3-5x a day by mouth for mouth infections, intestinal infection-3x per day. Shake bottle well before each use. Place half of the liquid on one side and the other half on the other side. Hold; swish it for several times in the mouth before swallowing. For intestinal use, just swallow liquid. Skin ointment or cream. Use several times a day. Wash thoroughly the affected area. Apply a small amount of the cream or ointment and gently massage it. Keep away from eyes . Powder. Dust the powder inside shoes and socks. Nystatin vaginal tab and cream. Use 001 BID as directed for vaginal infections. Use vaginal tab or cream for two week in women who are not pregnant and 3-6 weeks before delivery in pregnant women. Continue to use medication even if symptoms improve for a few days.

Reference:

CPS 2004 1308- 1309 Comprehensive Pharmacy Review, 5th Ed. Page 795. Comparison of FJuconazol And Ketoconazol Fluconazol

-

· · ·

·· · -

Triazole type antifungal Inhibitors of Ergosterol synthesis by binding to CYP Single doses Penetrate eNS (AIDS chemotherapy) CNS SE: dizziness No interaction with cimetidine, antacids For systemic infection UTI , peritonitis, pneumonia

Potent inhibitor of CYP 2C9 (high) and CYP3A4

Fluconazole taken with or without food.

·· · ·· · · ·

··

Ketoconazo! Imidazole type antifungal Inhibitor Ergosterol synthesis Not a single dose Doesn't penetrate eNS SE: Hormonal effects such as gynecomastia and menstrual disturbances Interaction with cimetidine, antacids Require acidic conditions for absorption (avoid antacids concomitantly) Potent inhibitor ofCYP 3A4 (high) and CYP 2C9 Ketoconazole taken with food or after food (with cola beverage if achlorhydric or on acid secrete suppressor)

Ketoconazole (Nizoral) Ketoconazole (Imidazole type)

Miconazole; Clotrimazole

Therapeutic use

Chronic mucocutaneous candidiasis, systemic and vaginal candidiasis, Tinea corporis (ringworm), T. cruris Gock itch), T. pedis (Athlete'S foot), Tinea versicolor (sun fungus), histoplasmosis, blastomycosis, paracoccidioidomycosis, oral thrush Relative bioavailability: 75 % with meals Available as tablet, cream

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Antifungals

www. PhannacvPrep.Com Mechanism

Block the symhesis of ergosterol 14a demethylase in the fu ngal CYP 450 complex; hepatic elimination

Side effects

Honnonal effects ? Decreased male libido and potency, gynecomastia, decreased plasma testosterone levels, affects female menstrual problems, Cardio effects ? hypertension, fluid retention, GI effects ? GI upset, hepatotoxicity, dizziness, anorexia, Nausea & Vomiting

Contraindication

Hypersensitivity; teratogenicity

WARNING

Rebound effect. Apply mild topical corticosteroids in the morning and ketoconazole at night and gradually decrease steroid over a period of2-3 weeks. Cross sensitivity

Precaution

Allergies with imidazoles

Counsell ing

Increased absorption on an empty stomach. Shampoo, I %: Wet scalp and work lather. Massage . Leave for 3-5 minutes then rinse zwell w ith wann water. Repeal application. Rinse and dry hair. Wash eyes if shampoo gels into them. Treatment is 2x a week for 2-4 weeks whereas as a prophylaxis, use once every 1-2 week; Shampoo, 2% : Wet hair and scalp. Apply shampoo the affected area. Work up lather and leave for 5 minutes. Rinse hair and scalp well. Dry hair. Protect eyes. Cream: Apply Ketoconazole cream to cover affected area and surrounding ski n areas. Rub gently. Keep using cream for the fu ll treatment even if symptoms begin to clear up after a few days to several weeks. Recurrent infection if you stop meds too soon . Do not miss a dose

References

CPS 2004, 1379-1380 Comprehensive Phannacy Review, jlh Ed . Page 794-795,

Fluconazole (Diflucan) Mechani sm

Block The Synthesis Of Ergosterol By Inhibit 14A-Demethy lase In The Fungal C YP450 Complex

Therapeutic use

Mucocutaneous Candidiasis (Esophageal); Alternative For Amphotericin B For Treatment Of Systemic Candidiasis, Cryptococcal Meningitis, Coccidioidomycosis, Cryptococcosis, HIV Associated Infections aRelati ve Bioavailability: 85- 92% With Meals

Side effects

Skin Rash GI Effects ? Nausea, Vomiting Diarrhea Or Commonly Causing G I Disturbances. Liver Effect ? Increase Liver Enzymes, Yellowing Of The Skin, And Eyes, Flu-Like Symptoms, CNS ? Dizziness, Headache, Exfol iative Skin Reactions, Altered Taste Buds, Extreme Tiredness, Seizures.

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Antifungals

Drug interaction

Decrease Levels With Carbamazepine, H2 Blockers, TN H, Phenytoin; Increase Levels Of Phenytoin, Warfarin, Sulfonylureas; ROH ; Anticancer Drugs, Amiodarone, Astemizole, Benzodiazepi ne, Cyc losporine, Disopyramide, OCP, D iuretics, Moxiftoxacin, Sotalol, Terfenadine, Quinidine, Valproic Acid, Thioridazine And Tacrolimus

Precaution

Decrease Elimination O f Enzyme Inducers Like Rifampin, Al lergies To Fluconazole And Other Antifungals, Irregular Heart Beat; Kidney Or Heart Disease

Reference:

Applied T. Handbook; Chapter. 67, Pp. 67.4 - 67.5 TC Page 4th Ed Page 1056.

Itraconazole (Sporanox) Therapeutic use

More active treatment against Aspergill us spp.; blastomycos is; other mycosis like mucor,Jusarium pseudoallescherria boydii; HIV associated infections; invasive and non-invasive pulmonary aspergi llosis; oral and esophageal candidiasis; chronic histoplasmosis (acute immunocompromised, an alternative to am photeri cin); cutaneous and lymphatic sporotrichosis; paracoccioi domycosis; chromomycosis Dose Aspergillosis: ;lOOmg IV Q8H X 12 H then 200mg IV Q l2H Blastomycosis; 200mg po BID Histoplasmosis: 200-400mg QD po Take wi th meals fo r adequate absorption

Mechanism

Bl ock the synthes is of ergosterol 14a demethylase in the fungal CYP 450 complexz

Side effects

Nausea, epigastric pain rash, headache, edema, hypokalemia, loss of appetite, shaking, dyspnea, bl eeding gums, yellowing of eyes and skin ; hypertriglyceridemia; decrease libido

Contraindication

CHF; Ventricular dysfunction

Warning

Cause CHF; heart attack; irregular heart beat! dse; lung! kidneylliver disease or other serious problems; SOB; coughing up white phlegm; weakness; excessive tiredness; fast heart beat; swelling ofthe feet, ankle or leg; sudden weight gain

Drug interaction

Cisapride, pimozide, dofet ilide, ergot meds, tri azolam, midazolam, quinidine, - all may cause irregular heart beat Take antacid one hour before or two hours after itraconazole

Drug interaction

Increased by Itraconazole: antiarrhythm ics, anticonvulsants-

CBl, antimycobacterial-ri fab utin, antineoplastics, antipsychotics, Benzodiazepine, Ca-channel bl ockers, gastrointestinal motil ity agents, HMG-CoA reductase inhibitors, Immunosuppressants, oral hy poglycemics, protease inhibitors, buspirone, macrolides; Decrease by Itraconazole anticonvulsant, anti mycobacterial, gastric acid suppressants, NN RTI

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Antifungals

Counselling

Oral solution: Sw ish 10ml (2tsp) in the mouth for a few seconds and swallow. Repeat is necessary until entire dose is taken. The solution is usually taken on an empty stomach once daily or 8lD for 1-4 weeks . Tell Doctor if taking Itraconazole. Do not substitute the capsules for the liquid because they have different use .

Reference:

CPS 2004, page 1973- 1978 Comprehensive Phannacy Review, 5111 Ed. Page 794-795

Clotrimazole Therapeutic use

Yeast infection, skin infections, high concentration needed in bacterial infection Availability: cream, lotion or solution- dennatophytes (ski n infections); intravaginal suppositories for vaginal candidiasis, lozenge

Mechanism

Block the synthesis of ergosterol 14a demethylase in the fungal CYP 450 complex Topical: blisters, edema, pruritus, burning, stinging, peeling skin tissue, increase urinary frequency Abdominal pain Irritation Abnormal liver function test in patient taking lozenge

Side effects

Contraindication

Not for first tri semester of pregnancy

Management

In case of vaginal infection, refrain from sexual intercourse cause an ingredient in the cream may weaken certain latex condoms / diaphragms . If first time of vaginal itching and discomfort. see a doctor. Do not use products within 72 hours of this med. Wear cotton unden . . ear and loose fitting pants; no lozenge for children under 3y/o Pregnancy

Precaution Reference

CPS, 2004 , 36\-362; Comprehensive Phannacy Review, 5111 Ed. Page 797

Miconazole Category

Broad spectrum fungistatic

Mechanism

Block synthesis of ergosterol by inhibiting 14a-demethylase in the fungal cytochrome P450 complex; selective inhibition of RNA & DNA and mucopolysaccharide precursor

Therapeutic use

Covers both dennatophytes and candidiasis (Advantage Over Tolnaftate and Nystatin; Also, effective against Tinea infections by T. pedis, T cruris, T. corporis, T. versicolor

Side effects

Itching, skin rash, Nausea &Vomiting, burning on the site of application

Contraindication

Sensitivity to any of the components of Miconazole, not for chi ldren> 2y/o unless directed by a doctor, do not use for the infection of the nail

Drug interaction

Anticoagulants, Phenytoin, Terbinafine,

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Antifungals

Drug interaction

Atypical anti-psychotics, Cyclosporins Some statins

Availability

Topical 2%, aerosol powder, 2 % cream, a kit-2% powder 2y/o and 2% tincture, 2% vaginal cream and 100 and 200 mg vaginal suppositories Aerosol powder Cleanse skin with soap and water. Dry thoroughly. Shake aerosol well before using. Apply or spray a thin layer over the affected area in the morning and up to bedtime. Do it from a distance of 6-10 inches to the affected area of the feet. Do not inhale powder. rf no improvement in 2 weeks time, see doctor But continue fir 1-2 weeks after symptoms disappear to a maximum of 4 weeks. Jock itch and ringworm is 1-2 weeks resolution; athlete's foot-4 weeks. Cream Apply sparingly, smoothen well and avoid maceration. Massage area gently. Athlete's f09t: dry feel, wear cotton socks CPS, 2004, page 1246

Application

Reference

Tolnaftate Category

Fungistic, fungicidal

Mechanism

Damage hyphae and stunt mycelial grO\vth in susceptible fungi

Therapeutic use

Jock itch, athlete's foot, ringworm ; T. pedis, M. canis, Aspergillus niger, C. a/bieans, M. gypseum, M. audounii, M.japonieum, T. rubrum, T,

Side effects Administration

Administration Warning Contraindication

mentagrophytes, T. sehonleinii, A./umigatus Slight irritation, sting (aerosol solution), burning and itching of athlete's foot and jock itch should decrease with in 2-3 days Do not apply dressings, or mix cosmetics or other skin medications with tolnaftate treatment. Powder: Clean and dry affected area. Sprinkle it bIn toes and in socks and shoes treated lightly. Spray should be shaken well before use. Apply it from a distance of at least six inches away. Continue treatment until symptoms disappear. A total of 4-6 weeks necessary. Do not inhale powder, bring close to a hot object or flame Cream. Thoroughly clean the infected area. Allow it to dry and then rub gently the medication until most of it disappears. Use sufficient quantity to cover the affected area. Wash hands after application. Solution. If it solidifies, dissolve by warming the closed container in warm water then follow dosage as directed. Usually, applied in affected areas 2x a day. Ifno effect in 4 weeks, check with health care professional. Aeroso ls: Flammable Allergies to tolnaftate or any preservatives, dyes; pregnancy; children, 2

y/o Reference:

Comprehensive Pharmacy Review, 5th Ed. Page 80 I

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Antifungals

Antifungals Tips Nystatin is indicated -7 Ketoconazole require acidic conditions for higher bioavai lability therefore -7 Meningitis fungal infections other eNS infections can be treated bY-7 If a chi ld swallowed 5g of nystatin, and parents are panic, comes to your phannacy, what is appropriate action -7 Nystatin is ineffective for -7 DOC for oral thrush-7 DOC for vaginal candidasi s Topcal Drug of choice for Atheletes foot -7 Nystatin suspension counseling-7 Amphotericin - B is -7 act by inhibiting the cell membrane function

Abbrevation and Tenninology GIT YF

HTN SJS CSF ACTH AZT OCP NN RTI IV CYP SOB CBZ BID CPS

Generic and Brand Amphotericin B Nystatin Fluconazole Itraconazole Clotrimazole Miconazole Tolnaftate

Fungistic, Fungicidal Tri-Statin, Mycolog, Mytrex Diftucan Sppranox Clotrimazole Cruex Lotrimin M celex Aloe Vesta Cruex Desenex Jock Itch Asorbine Afate. Genas ore Pitrex

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Ami-Mycobacterial Drugs

40

Anti-Mycobacterial Drugs Antimycobacterial drugs Isoniazid Rifampin Streptomycin Pyrazinamide Ethambutol Capreomycin Rifabutin Tuberculosis treatment: Goal of treatment is must eradicate mycobacterium. Important issues in tuberculos is treatment are resistance to drugs . ·.-Drugs that haveJowest resistancejs:lsoniazid, rifampin, streptomycin and combination of these drugs with pyrazinamide, or ethambutol. Drug of choice is combination of Isoniazid + rifampin + pyrazinamide. Antimycobacterial Drugs Rifampin Chemical structure ofrifampin is a macrocyclin. This drugs is bactericidal Inhibits RNA synthesis Mechanism Therapeutic Use Effective against M. tuberculosis, and M. leprae Prophylactic for house hold members of exposed to meningitis caused by meningococci or H. influenza type b Side Effects Seri ous liver toxicity (hepatotoxicity) thereby LIT should be performed regularly Gr SE: nausea, vomiting, abdomil!al pail! CNS SE: Headache, drowsiness, confus ion, fatigue Rifampin discolor urine, sweat, tears, saliva and feces to orange-red . Drug interactions Rifampin is inducer ofCYP IA2, 206, 2C9, 2C19, 3A4 Reduce efficacy oral contraceptive. Isoniazid (INH) Mechanism Therapeutic Use Side Effects

Chemical structure is hydrazide of isonicotinic acid. Targets enzyme responsible for mycolic acid synthesis First line treatment for tuberculosis Most common: Peripheral neuritis (because of pyridoxine deficiency) Vitamin 8 6 supplements. Skin rash, jaundice and fever are common SE. Supplementing breast fed mothers can provide pyridoxine deficiency in ch ildren.

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Anti-Mycobacterial Drugs Most common: Hepatitis: Most severe-fatal, the risk of hepatitis increases with patient age and alcohol abuse. Monitor LFT Blood dyscariasis (agranulocytosis, aplastic anemia, hemolytic anemia Thrombocytopenia) thereby monitor CBC routinely eNS toxicity due to decrease in pyridoxine levels: Administer 15 -50 mgldy pyridoxine to minimize the peripheral neuropathy. Symptoms of CNS toxicity are: insomnia, restlessness, hyperreflexia, and convulsions.

Pyrazinamide (ZIN)

It is pyrazine analog of nicotinamide

Mechanism

Pyrazinamidase enzyme converts into pyrazinoic acid (active fonn)

Therapeutic Use

Combination with INH and rifampin. Pyrazinamide has activity only against M.Tuberculosis Liver dysfunction Urate retention . May precipitate gouty attacks

Side effeclS

Antimycobacterials Tips Drugs that discolor urine, tears, saliva, feces, sweat ? Drug of choice to treat tuberculosis ? Peripheral neuritis caused by isoniazid can managed by administering ? XDR TB = Extensive Drug Resistance Tuberculosis. All antitubercular drug should be taken on :

Abbrevation and Tenninology TNH LFT

Isoniazid ·Li ver Funtion Test

XDRTB ZIN

Extensive Drug Resistance Tuberculos is. Pyrazinamide

CYP

Generic and Brand Isoniazid Ri fampin Streptomycin P razinamide Ethambutol Capreomycin Ri fabutin

Isoniazid INH Nvdrazid Ri fadin Rimactane Myambutol Mycobutin

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Anti-viral Drugs

41

Anti-viral Drugs Antiviral Agents

Amant.din<

~Iovir

lidovudine

Ne,u apint

Rimantadirr

VolK)'Clow Ganciclo, u

Didano