PBL(1L) Pharmacology

Pharmacology - Chapter 8 Includes all nerves traveling between the CNS and somatic and visceral sites? Includes the diencephalon, cerebrum, cerebellum, brainstem, and spinal cord? Responsible for perception, wakefulness, language, and consciousness? Sensory neurons arise principally from what? Sensory cell bodies and nuclei are located where? Sensory neurons project onto neurons located where? Somatic motor neurons arise from where? Somatic motor neurons exit through what? Somatic motor fibers join with what? Somatic motor fibers innervate what? Sympathetic PreG arise from where? Adrenal Medulla is innervated by what? Parasympathetic preganglionic neurons arise from where? Where are parasympathetic ganglia located? Cell bodies for the preganglionic sympathetics are located where in the spinal cord, specifically? Consists of 25 pairs of interconnected ganglia that lie on either side of the vertebral column? SNS ganglia that innverates pupil, salivary gland, lacrimal gland, blood vessels and sweat glands in head and face? PostG neurons arising in the middle/inferor cervical + thoracic ganglia, innervate what? Adrenal medulla contains what type of cells? Sympathetic agonist that can dilate the brochioles selectively? Sympathetic antagonist that can selectively decrease the heart rate and contractility? PreG fibers from CN III arise from a midbrain region called the? PSNS Antagonist used locally to dilate the pupils or systemically to increase heart rate? PSNS antagonist used to dilate the bronchioles? Motor Cortex -> cross the medulla -> Descend through the cord to other neurons in ventral horns? Motor neurons in the ventral horn? Projections that exit the ventral roots and mix with sensory are called? Ascend through the dorsal columns in the SC and synapse with secondary neurons in the contralateral medulla? Synapse with secondary neurons in the posterior horn of the SC, cross in SC, ascend contralateral spinothalamic tract? Both the spinothalamic tract and dorsal column tract connect with third order neurons in the? Antagonists of NMJ activity used for paralysis during surgery? Increase NMJ activity and used in the diagnosis of Myastenia Gravis Commonly prescribed hypnotics and sedatives that potentiate the action of inhibitory NTs in the cortex? Consists of myelined axons that have an associated vascular network? Caused by degeneration of a dopaminergic pathway that arises in the substania nigra in the midbrain? A component of sinemet medication that acts on the striatum to ameloriate symptoms of parkinsons? Caused by degeneration of the hippocampal formation? Many drugs of abuse stimulate the brain-reward pathway, which includes a specific structure noted in the text? Not simply a signal relay, rather it filters and modulates sensory information - which signals reach conscious awareness? Neurons in the periaquaductal gray, send projections to the SC that modulate what?

Peripheral Nervous System CNS CNS Skin and Joints DRG Dorsal horn of the spinal cord Ventral horn of SC Ventral roots Sensory fibers to form Spinal nerves Skeletal muscle Ventral horm of Thoracic and Lumbar -> project onto Paravertebral or Prevertebral Ganglia PREGANGLIONIC sympathetic neurons nuclei in the BS and sacral segments of SC Near the innervated organs Intermediolateral columns (T1-L2/3) Sympathetic Chain Superior Cervical Ganglia Heart and Lungs Postsynaptic Neuroendocrine Cells Albuterol Metoprolol Edinger-Westphal Nucleus (cause pupil to constrict) Atropine Ipratropium First order neuroms Second order neurons Spinal nerves Position and Vibration sense Temperature and Pain sense Thalamus Pancuronium Edrophonium and Neostigmine Barbiturates and Benzodiazepines White Matter Parkinsons Disease Levadopa Alzheimers Nucleus Accumbens Thalamus Pain reception

Responsible for consciousness and sleep regulation? Each nuclei in the reticular formation uses a different what? Via this NT systems difference, what will cause sedation? Via this NT systems difference, what will cause heightened alertness? Important target for opiods due to the fact that it carries sensory signals, such as those for pain? What type of neuronal organization involves neural pathways that connect distant areas of the NS to one another? Which system is designed exclusively as a long tract system? In the PNS, signals are transmitted with very little what? One PreG neuron synapsing with numerous postG neurons? CNS LT neurons use divergent, but all receive information from numerous upstream neurons, called? Strategy that uses both excitatory and inhibatory NT to localize a signal Local circuit neurons show a complicated what? The local circuit is arranged in layers and includes both what? What are the local circuits used for? Typically originate in the nucleus in the brainstem and have axonal terminals that innervate thousands of neurons? Single source systems are usually called what? Neurons constituting single source divergent circuits do not usually have what? Why do they not have myelin sheaths? NT for substania nigra? Function of the substania nigra? NT for Locus Ceruleus (Pons) Function of the LC in the Pons? NT for Raphe Nuclei (Medulla, Pons, Midbrain)? Function of the Raphe Nuclei? Dysfunction of the serotonin system causes what? Antidepressants block what? Blockage of this will cause what to be activated? Neurons that innervate sweat glands? Which two NT are used by the PNS? Is neither an AA nor a biogenic amine? Are the primary excitatory and inhibitory NTs in the CNS? Glutamate and Aspartate are primarily what? GABA and Glycine are primarily what? One of the mechanisms by which icschemic injury causes neuronal death? Used in the treatment of refractory epilepsy, inihibits the NMDA receptor, reduces seizures? Several classes of barbiturates and benzodiazopenes bind to what receptors? Catetcholamines are derived from? Indoleamine Serotonin is synthesized from? Histamine is derived from? Why is dopamine not an effective therapy for Parkinsons? Dopamine precursors and dopaminergic receptor antagonist are used in the treatment of what disease? Dopamine receptora antagonsits can also be used in the treatment of what? Where is dopamine synthesized? Dopamine is converted to NE via what enzyme? NE can be transported back into the what? In the cytoplasm, it can be methylated to form? Partial agonist that acts on presynaptic α2 receptors?

Reticular Formation NT system Anithistamines Cocaine SC Long tract PNS Modification Divergent Signalling Convergent Signalling Center-surround signalling Structural motif excitory and inhibitory neurons Processing information Single-source Diffuse system of organization Myelin sheaths Modulatory influence change over longer periods of time (rather than fractions of seconds) Dopamine Enable intended motion, emotion, thought, and memory storage NE Vigilance, responsiveness to unexpected stimuli Serotonin Perception of Pain Depression Reuptake of serotonin The serotonergic system PostG SNS Ach and NE Ach AA NTs Excitatory Inhibitory Excessive excitation of certain glutamate receptors Felbamate GABA Tyrosine Tryptophan Histidine Can't cross the BBB Parkinsons Disease Schizophrenia Cytoplasm Dopamine B-hydroxylase Cytoplasm Epinephrine Clondine

Antidepressant that increases synaptic NE by blocking its reuptake Antidepressant that increases intracellular pool by blocking NE degradation? TCAs block NE reuptake and uptake of what other NT? Drug that is used to "brighten" patients with dementia, it’s a AChE Inhibitor? Anti-muscarinic that can cause drowsiness, amnesia, and dreamless sleep? Cholinergic antagonist that can cause adverse effects of cotical arousal and alertness? Competitive antagonist at adenosine receptors and mild stimulant? Adenosine receptors are located where? Antagonism of these receptors leads to disinhibition of NE and subsequent what? Receptors for NO are thought to reside where? NO acts as a what? Opioid receptors are principally located where? Protects the brain from toxic effects of chemicals like NE, E, Glutamate and Dopamine? Small gaps b/n endothelial cells that allow water and small ion passage but filter large proteins and cells? Instead of fenestrae, the CNS endothelial cells have what CNS Endothelial also do not have these, which transport fluid from the blood vessel lumen to the extracellular space? Glucose would not be able to tranverse the barrier without what? What secretes cellular processes that cover the endothelium of the CNS? What transports L-DOPA across the barrier? Medications for Parkinsons that contain L-DOPA can be affected by meals that are heavy in what? Why does this affect the parkinsons medications? What is DOPA decarboxylase? What is carbadopa?

TCAs MAOIs Serotonin Donepezil Scopolamine Pilocarpine (drool, tear and sweat) - Sjogrens Caffeine Presynaptic noradrenergic neurons Release of NE Presynaptic neurons Retrograde messenger Spinal cord BBB Fenestrae Tight junctions Pinocytotic vesicles Hexose Transporters (facilitated diffusion) Astroglia Large AA transporter Protein The AA transporter can become overwhelmed Converts LDOPA -> DOPA Inhibits DOPA decarboxylase to ensure that LDOPA does not get converted to something that can not cross the BBB, like DOPA

Pharmacology - Chapter 26 GH is secreted in large amounts during what life period? When do the largest pulses of GH get released? What mediates the effects of GH? What is IGF-1? Can IGF-1 be measured? When it is helpful to be measured? Name some environmental factors that stimulate the release of GH? Name some endogenous biological factors that stimulate the release of GH? What is ghrelin? What does grehlin act synergistically with? What secretes ghrelin? During what state is ghrelin released, fasting or fed What are the most significant endogenous factors that inhibit GH release? GH deficiency commonly results from what? In GH insensitivity, what is reduced? Secondary GH deficiency? Teritary GH deficiency? GH excess? GHRH analogues (for the treatment of GH or IGF-1 insufficiency)?

Recombinant HGH? Diagnosis required for HGH treatment? Name for recombinant IGF-1? Mecasermin is approved to treat what? Gigantism? Acromegaly? Mainstay of medical therapy to treat GH excess? Synthetic long-lasting analogues of somatostatin?

Side-effects of GH excess medial therapy? Dopamine analgogues for the medical treatment of GH excess? What are dopamine analogs used to treat? Are dopamine agonists more or less effective than SRLs? How many binding sites does the GH molecule have? What must occur to activate the receptor? Which drug binds to one of the sites with higher affinity than GH and blocks dimerization? Which drug has the most potent IGF-1 reducing ability? What is the side effect of this potent IGF-1 reducing ability? Lactotrophs produce and secrete? What is different about lactrotroph than the other cells of the anterior pituitary? What stimulates prolactin release? Patients taking phenothiazine (anti-psycho) or metoclopramide experience what?

Puberty At night IGF-1 A hormone released into the circulation by hepatocytes in response to stimulation by GH a bound and stable protein in the circulation at steady concentrations In the diagnosis of acromegaly hypoglycemia, sleep, exercise, and adequate nutritional status hypothalamic GHRH, sex steroids, dopamine, ghrelin important endogenous growth hormone-releasing peptide with GHRH to promote the release of GH (acts on a receptor that is different from GHRH's receptor) Gastric Fundal Cells Fasting, links growth with nutritional status and energy balance Somatostatin, IGF-1, and GH defective hypothalamic release OR pituitary insufficiency IGF-1, GH is secreted but the liver is unresponsive to the it's effect Unresponsive Anterior Pituitary, secretes reduced amounts of GH Lack of GHRH from the hypothalamus -> less GH -> less IGF-1 Usually from adenoma of the anterior pituitary, negative feedback of increased IGF-1 is shot. Sermorelin (synthetic GHRH) - currently unavailable Tesamorelin (novel GHRH analogue) - Augments basal and puslatile GH secretion Glucagon Insulin-induced hypoglycemia Arginine Clonidine Somatotropin confirmed GH deficiency or panhypopituitarism Mecasermin Laron Dwarfism (GH insufficiency) IGF excess occurs before the epiphyses close, increased longitudinal growth IGF excess after the epiphyses close, increased hand thinckness, shoe size, fatigue and hyperhidrosis SRLs (Somatostatin Receptor Ligands) Octreotide Lanreotide Pasireotide (Investigational) Nausea, diarrhea, gallstones, and headache Bromocriptine Cabergoline Acromegaly Less effecitve, usually used as a second line treatment 2 Dimerization Pegvisomant Pegvisomant increased GH levels due to lack of IGF1 negative feeback Prolactin Under tonic inhibition by dopamine TRH and estrogen Increased prolactin levels

Why would they experience this? Increased prolactin levels suppress what? Prolactinomas are common cause of what? Category A medical treatment for prolactinomas? Major adverse effects of bromocriptine? Which dopamine receptor agonist can be given bi-weekly? Which dopamine receptor agonist is commonly used in Europe? Which dopamine receptor agonist is commonly given to pregnant women? What other disease is cabergoline used to treat? Disease state in which serum TSH is high? In secondary thyroid hormone deficiency would TSH levels be high? Commonly used drug during radioactive iodine treatment of thyroid cancer? Neurons from the paraventricular nucleus of the hypothalamus synthesize and secrete? CRH stimulates the Ant. Pit. To release what? ACTH is synthesized as part of? Cleavage of POMC yeilds? Structural similarities in ACTH and MSH allow what? Why is this clinically relevant? Primary Adrenal Tumor that secretes mass Cortisol independent of ACTH? Pituarty Adenoma that secretes mass ACTH -> increased levels of cortisol? Ectopic ACTH-secreting tumor? Synthetic form of ACTH used to diagnose adrenal insufficiency? Cosyntropin + Primary Adrenal Insufficency = ? Cosyntropin + Secondary Adrenal Insufficency = ? Drugs that can be used to reduce cortisol production (treat Cushing's S/D) How do these drugs work? Which drug antagonizes the cortisol binding site in peripheral tissues? GnRH is secreted by the hypothalamus in a ? GnRH stimulates what LH and FSH stimulate what? Follicles induce a postive mid-cycle in increase in what? Inhibin is produced by the gonads in response to FSH and exerts a _______ feedback on gonadatrophs to inhibit FSH? Activin stimulates what? Pulsatile GnRH? Continuous GnRH? Purified FSH from the urine of post-menopausal women? Recombinant FSH? Inherited mutation in the FSH receptor that allows HCG to activate it? Used to surpress premature surges in LH - assited reproduction ADH is produced by what type of cells? Increased osmolarity stimulates what? ADH binds to what receptors? Where are v1 receptors located? What do they cause? Alternative name for ADH? Two actions of ADH? Are located in the nephron and stimulate cell surgace expression of water channnels in order to increase h20 reabsorb? Excessive secretion of ADH Deficient secretion of ADH

Those drugs are dopamine receptor antagonists Estrogen synthesis Infertility Bromocriptine Nausea, vomitting - GI issues Cabergoline Quinagolide Bromocriptine Parkinsons (high doses - associated with heart valve issues) Primary Thyroid Deficiency No, both TH and TSH would be low Thyrotropin (Recombinant TSH) CRH ACTH POMC MSH, Lipotropin, and β-endorphin ACTH to bind to MSH receptors Primary Hypoadrenalism, increase ACTH result in enhanced skin pigmentation Cushing syndrome Cushing disease Causes increased ACTH and Increase coritsol levels Cosyntropin No increase in Cortisol Robust increase in Cortisol Metyrapone, Ketoconazole, and Mitotane Inhibit steroidogenesis in the Adrenal Glands Mifepristone Pulsitile fashion Gonadotroph cells of the Ant. Pit. To secrete LH and FSH Ovaries/Testes to produce sex hormones estrogen/testosterone FSH and LH Negative FSH secretion Stimulate FSH and LH Inhibits FSH and LH release Urofollitropin follitropin Ovarian Hyperstimulation Syndrome Cetrorelix and Ganirelix Magnocellular cells Stimulates ADH secretion from nerve terminals in PPG V1 and V2 receptors systemic arterioles vasoconstriction Vasopressin 1. Increase BP 2. Increase Water Reabsorb V2 receptors SIADH Diabetes Insipidus

Most common cause of SIADH? Excessive ADH secretion results in persistnat stimulation of what? What does this cause? What do you use to treat SIADH? Vasopressin receptor antagonists? V2 specific Vasopressin receptor antagonist approved for the use in Heart Failure? Mixed v1 and v2 vasopressin receptor antagonists? Results from inability of hypothalamic neurons to secrete ADH? Used to treat Neurogenic Diabetes insipidus? Results from mutated v2 receptor (collecting duct) in which ADH is unable to bind to the receptor or stimulate signalling? Used to treat Nephrogenic Diabetes Insipidus? Action of these drugs?

Ectopic secretion of ADH from a small cell carcinoma of the lung V1 and V2 receptors Hypertension and Excess water retention Vasopressin receptor antagonists 1. Conivaptan 2. Tolvaptan Tolvaptan Conivaptan Neurogenic Diabetes Insipidus Desmopressin Nephrogenic Diabetes Insipidus Amiloride and Hydrochlorothiazide Increase water reabsorption at the PROXIMAL TUBULES

Pharmacology - Chapter 30 GLP-1 does what? Counter-regulatory hormones do what? Why is hypoglycemia so dangerous? Why is chronic hyperglycemia so dangerous? Which organ receives the highest concentration of Insulin concurrently with nutrients absorbed from GI tract? Which organs are the primary targets for insulin? Leptin plays a role in what? Leptin is secreted from what? Leptin's concentration in the plamsa is proportional to what? Leptin also supresses what? This suppression switches the body from energy accumulating state to? Is a transcription factor that serves as the master regulator of adispose differentiation? Activation PPARγ decreases serum FA levels and promotes what? Lowering the fat content of the liver and skeletal muscles increases these tissues sensativity to what? PPARγ is the target for what class of drugs? Secreted from α-cells? Secreted from β-cells? Secreted from β-cells? Secreted from δ-cells, GI tract, and Hypothalamus? Secreted from the Adrenal Medulla? Secreted from the Adrenal Cortex? Secreted from the Ileum? Secreted from Adipocytes? Promotes glycogenolysis and gluconeogenesis? Promotes uptake of glucose, AA, and FA from blood into cells for storage as glycogen, protein, and triglyceride? Decreases the release of Insulin and Glucagon, Decreases GI tract motility and hormone release, decreases GH? Antagonizes insulin at target tissues, promotes gluconeogenesis in liver and protein breakdown in muscle? Signals adequacy of body energey stores, decreases food intake, and permits energy intensive neuroendocrine functions? Surpresses glucagon release, slows gastric emptying, and decreases food intake? Promotes glycogenolysis in liver and lipolytic via activation of hormone senstitive lipase? Increases β-cell mass and insulin secretion, delays gastic emptying, and decreases food intake and glucagon secretion? Amylin primarily acts where? Somatostatin primarily acts where? What substance discussed above works on the endocrine pancreas, stomach, brain and heart? What has a primary site of action at the CNS (basomedial hypothalamus)? In low energy states, what enzyme triggers a shift from anabolic to catabolic activities? Breaks down dietary complex carbohydrates into simple sugars in the GI brush border? Glucose metabolism in β-cells increases what to trigger insulin secretion? Promotes the conversion of glucose into TGs in adipocytes? Glucose enters β-cells via a specific transporter? Drugs that delay gastric emptying? Drugs that inhibit α-glucosidases? Drugs that augment (increase) insulin secretion?

Enhances insulin release in response to an ingested meal oppose the action of insulin and promote the release of nutrients Because organ, especially the brain, rely on constant supply of glucose for fuel Hyperglycemia is toxic to many cells Liver Energy-storing tissues: muscle, adipose tissue Neuroendocrine response to Energy storage and LT energy balance Adipocytes Total fat mass appetite Energy utilization PPARγ lipogenesis in adipose tissue Insulin TZD's (thiazolidinediones) Glucagon Insulin Amylin Somatostatin Catecholamines (E) Cortisol (ZF) GLP-1 Leptin Glucagon Insulin Somatostatin Cortisol Leptin Amylin Epinephrine GLP-1 CNS Other Islet cells, GI Tract, Brain, and Pituitary GLP-1 Leptin AMPK Glucosidases ATP PPARγ GLUT2 GLP-1 analogue or amylin analogue α-glucosidase inhibitor sulfonylureas, meglitinides, or incretins

Drugs that suppress glucagon and gluconeogenesis? Drugs that enhance the action of insulin in adipose cells? Is a second messanger protein for many aspects of insulin action? Insulin stimulates the movement of this transporter to the membrane of skeletal muscle and adipose tissue? Insulin promotes what in adipose tissue that results in increased uptake of TAGS into fat cells? Degrades insulin rapidly in the liver and kidney (1/2 life of only 6 minutes)? Autoimmune destruction of pancreatic β-cells? Insulin resistance, with adequate β-cell function to compensate? Age of onset < 30 y/o? Insulin ressitance is present? Ketoacidosis and Acute wasting are the acute complications? Hyperglycemia is the acute complication? Chronic complications include: Neuropathy, Retinopathy, Nephropathy, Peripheral Vasucular Disease, CAD? Pharmacologic intervention is mostly insulin replacement therapy? Pharmacologic intervention include combination therapy with insulin and a number of other classes of drugs? Insulin action is completely absent or negliable? Insulin action is just decreased? Insulin levels are typically higher than normal?

Incretins, amylin analogues, biguanides TZD's (thiazolidinediones) PI3-kinase GLUT4 Lipoprotein Lipase Insulinase enzymes Type 1 Type 2 Type 1 Type 2 Type 1 Type 2 Type 1 and Type 2 Type 1 Type 2 Type 1 Type 1 Type 2