Drugs Block 2

Question 1

Acetylcholine

Answer 1

Agonist of nicotinic/muscarinic receptors. Muscarinic effects are elicited by lower concentrations of ACh than needed for nicotinic effects. ACh binds M3 receptors which promotes EDRF/NO relaxation of smooth muscle in arterioles, thereby decreasing BP.

Question 2

Botulium Toxin A (Botox)

Answer 2

Blocks Ca2+ mediated exocytosis of ACh from pre-synaptic terminal. FDA approved to tx muscle spasms.

Question 3

Pralidoxime

Answer 3

2nd line treatment for organophosphate toxicity; used along with atropine to treat cholinesterase inhibitor poisoning. Works by reactivating cholinesterases that were inhibited by anti-cholinesterase.

Question 4

Nicotine

Answer 4

A nicotinic agonist that acts on autonomic ganglia, adrenal medulla, neuromuscular jxns, and the brain. CV effects include peripheral vasoconstriction, tachycardia, and elevated BP. Used for smoking cessation.

Question 5

Succinylcholine

Answer 5

nAChr agonist that causes transient depolarization, followed by desensitization of ACh channels; keeps EPP depolarized as long as it is bound to nAChr (and not broken down by AChE, so long-lasting) thereby inactivating surrounding sodium channels, which cannot recover till EPP repolarizes. Used as a depolarizing block, often in emergent intubating due to fast onset of paralysis.

Question 6

Varenicline

Answer 6

aka Chantix; partial agonist of nAChR; primary effects are CNS, used for smoking cessation.

Question 7

Rocuronium

Answer 7

competitive antagonist of nicotinic-ACh receptor; used to produce non-depolarizing block (muscle paralysis) during surgery

Question 8

Cistracurium

Answer 8

a competitive antagonist of nicotinic-ACh receptor; used to produce non-depolarizing block (muscle paralysis) during surgery; metabolized differently than rocuronium.

Question 9

Trimethaphan

Answer 9

a short acting antagonist of ganglionic nicotinic receptors; blocks transmission in parasympathetic and sympathetic ganglia; used for hypertensive emergencies and autonomic testing.

Question 10

Pilocarpine

Answer 10

mAChR agonist used to tx glaucoma; causes pupillary constriction and increased ciliary muscle tension that are thought to improve drainage oand decreased pressure; readily absorbed due to lack of 4’ ammonium group.

“You cry, drool, and sweat on your PILOw.”

Question 11

Atropine

Answer 11

Muscarinic competitive antagonist, highly specific; used to tx bradycardia (works by increasing HR) in emergent situations; also used to counteract bronchoconstriction during intoxication with anticholinesterases. Does NOT change BP.

Generally safe to use, but dose-limiting side effects include xerostomia (dry mouth), photophobia, and difficulty in accommodation.

Contraindicated in pt’s with glaucoma (can increase intraocular pressure) and prostatic hypertrophy (can cause difficulty in voiding)

Question 12

Glycopyrrolate

Answer 12

Muscarinic antagonist that reduces GI and respiratory secretions; used pre-operatively to reduce airway secretions as well as to treat drooling and peptic ulcers.

Question 13

Scopolamine

Answer 13

Muscarinic antagonist used to prevent motion sickness; also can be used as a preanesthetic medication for sedation and amnesia.

Question 14

Tiotropium

Answer 14

AKA Spiriva; muscarinic antagonist (somewhat selective for M3) used to tx COPD; opens airways and reduces phlegm; longer-lasting than ipratoprium

Question 15

Edrophonium

Answer 15

Anticholinesterase; increases endogenous ACh levels; used to dx myasthenia gravis; extremely short acting

Question 16

Neostigmine

Answer 16

Anticholinesterase; increases endogenous ACh; used post-operatively to reverse NMJ blockade and tx neurogenic ileus and urinary retention; also used to tx MG; NO CNS Penetration

Question 17

Physostigmine

Answer 17

Anticholinesterase; increases endogenous ACh; used to tx atropine overdose; crosses the BBB;

Physo– “phyxes” atropine overose.

Question 18

Pyridostigmine

Answer 18

Anticholinesterase used to tx MG; increases endogenous ACh and increases muscle strength; long-lasting; does not penetrate CNS.

Question 19

Sarin

Answer 19

typical organophosphate anticholinesterase, binds esteratic site via PO43-

Question 20

Malathion

Answer 20

Anticholinesterase; thiophosphate insecticide, used in humans to tx head lice; generally safe because even though malathion (inactive form) gets converted to malaoxon (active form) by desulfuration, malaoxon is hydrolyzed (inactivated) even more quickly, so there is no build up of active product.

Question 21

Albuterol

Answer 21

selective B2 adrenergic agonist; used for fast-acting bronchodilation for acute asthma attacks; only relative selectivity for B2 (over B1) so get cardiac and CNS stimulation.

Question 22

Amphetamine

Answer 22

AKA Benzedrine; Indirect acting sympathomimetic that indirectly releases NE; possesses CNS stimulating-activity; used to tx narcolepsy and hyperkinetic syndrome in children; adverse effects include tolerance, dependence, psychological issues, CV stimulation, CNS stimulation, mydriasis and dry mouth.

Question 23

Atenolol

Answer 23

selective B1 antagonist used as:

antiarrhythmic and antianginal [decreases heart rate, contractility, output, conduction velocity and automaticity];

used to HTN and migraine HA’s [may decrease BP with long-term use]

used to tx glaucoma [decreases intraocular pressure]

Also increases airway resistance and inhibits glycogenolysis (resulting in hypoglycemia).

Question 24

Clonidine

Answer 24

A2 agonist; inhibits NE release, decreases sympathetic outflow from CNS; used to tx HTN; side effects include dry mouth, sedation, constipation, rebound hypertension.

Question 25

Cocaine

Answer 25

Indirect sympathomimetic which indirectly blocks NE reuptake, elevates extracellular NE; no therapeutic uses although was used as local anesthetic in past.

Question 26

Dobutamine

Answer 26

B1 agonist; used to improve myocardial fxn in heart failure; has greater inotropic than chronotropic effects; not absorbed orally, 1/2 life of only 2 minutes following IV administration; side effects include tachycardia, hypertension, arrhythmias

Question 27

Dopamine

Answer 27

Endogenous precursor for NE; dopamine is hydroxylated by dopamine Beta-hydroxylase to produce NE; occurs within exocytotic vesicle;

Has indirect sympathomimetic action—promotes release of NE from cytosol of neuron; activates Dopamine 1 & 2 receptors in periphery

At high doses, directly activates alpha-1 adrenergic receptors producing vasoconstriction with reduction in renal blood flow.

At low-moderate doses directly activates beta-1 receptors, reducing arterial resistance in mesentery and kidney (used in shock) plus inotropic effects.

Used to tx cardiogenic shock, septic shock, and chronic refractory heart failure.

Question 28

Doxazosin

Answer 28

A selective alpha-1 antagonist; which reduces alpha-1-mediated smooth muscle tone in prostate and bladder and arterioles; used to tx benign prostatic hyperplasia (BPH) and HTN.

Question 29

Ephedrine

Answer 29

Indirect promoter of NE release from cytosol of neuron; also can directly stimulate Beta2 and Alpha1 receptors; actions similar to Epinephrine (though response is slower onset and longer lasting when IV administered); resistant to COMT and MAO degradation; increases arterial pressure (alpha-1) and relaxes bronchial smooth muscle (beta2); also produces mydriasis (alpha-1); CNS effects including insomnia, nervousness, agitation, nausea; well absorbed orally; tachyphylaxsis (resistance) occurs with repeated administration.

Used to tx bronchial asthma (historically), used as a nasal decongestant, pressor agent in spinal anesthesia; used as mydriatic agent.

Question 30

Epinephrine

Answer 30

Adrenergic agonist; many effects:

Blood Pressure: low doses decrease BP (Beta 2), high doses increase BP (alpha 1 vasoconstriction, beta 1 positive inotropic); HR initially increases, by will slow once baroreflex kicks in

Vasculature: tissue specific expression of alpha1/beta2 regulates effect of Epi on vasculature. See increased blood flow to skeletal muscle at low concentrations, and decreased flow at high concentrations (Beta 2). In most other tissues/organs, will see vasoconstriction (alpha 1). In Alpha-2 receptors, will stimulate platelet aggregation.

Heart: Epi has positive chronotropic, dromotropic, inotropic effects (Beta1); propensity towards arrhythmias.

Smooth muscle: via Beta 2 see relaxation of bronchi, GI, uterus (non-pregnant); via Alpha 1 see increased GI sphincter constriction and increased uterine ctxns (pregnant); also see GI smooth m. relaxation with alpha-2.

Metabolic: increased glucose/lactate production via liver and muscle glycogenolysis (beta 2); increased FA’s (beta-3), inhibition of insulin secretion (alpha-2), increased O2 consumption

Therapeutic uses: tx of bronchospasm, relief of hyperensitivity rx, prolonged duration of infiltrative anesthesia (vasoconstrictive), restore cardiac activity in cardiac arrest and heart block.

Adverse Effects: anxiety, HA, cerebral hemorrhage.

Question 31

Isoproterenol

Answer 31

Non-selective Beta agonist; IV infusion results in reduced peripheral vascular resistance in skeletal m., and in renal and mesenteric vasc. beds; diastolic pressure falls, but CO increases due to increased venous return and positive inotropic/chronotropic effects; mean BP decreases (though systolic may rise); relaxation of bronchial and GI smooth muscle; increased release of FA’s while hyperglycemia is less than with Epi

PO absorption is erratic; parenteral injection/inhalation results in fast distribution; metabolized by COMT;

Used as bronchodilator and cardiac stimulant

Adverse effects: similar to Epi; overdose –> fatal arrhythmias; tolerance to bronchial actions can occur with overuse.

Question 32

Labetalol

Answer 32

nonselective Beta-1 and Beta-2 (and Alpha-1) antagonist; antiarrhythmic and antianginal [decreases heart rate, contractility, output, conduction velocity and automaticity];

used to HTN and migraine HA’s [may decrease BP with long-term use]

used to tx glaucoma [decreases intraocular pressure]

Also increases airway resistance and inhibits glycogenolysis (resulting in hypoglycemia).

Question 33

Methoxamine

Answer 33

Alpha-1 agonist; used as nasal decongestant (contraction of nasal mucosal vascular smooth muscle which reverses hyperemia); induces mydriasis

Question 34

Metoprolol

Answer 34

Beta-1 antagonist; antiarrhythmic and antianginal [decreases heart rate, contractility, output, conduction velocity and automaticity];

used to HTN and migraine HA’s [may decrease BP with long-term use]

used to tx glaucoma [decreases intraocular pressure]

Also increases airway resistance and inhibits glycogenolysis (resulting in hypoglycemia).

Question 35

Norepinephrine

Answer 35

Adrenergic agonist (except poor agonist at Beta 2); increase BP by vasoconstriction (alpha 1 and somewhat alpha-2); reduces HR due to baroreceptor reflex responding to increased peripheral vascular resistance; used to tx hypotension

Adverse effects: anxiety, HA, cerebral hemorrhage, cardiac arrhythmias, pulmonary edema.

Question 36

Phentolamine

Answer 36

Competitive alpha antagonist (non-selective for alpha type); used in tx of catecholamine excess; adverse effects include postural hypotension and tachycardia (reflex stimulation)

Question 37

Phenylephrine

Answer 37

Alpha-1 agonist; used as nasal decongestant (contraction of nasal mucosal vascular smooth muscle which reverses hyperemia); induces mydriasis

Question 38

Prazosin

Answer 38

Selective alpha-1 antagonist; equilibrium competitive; at high doses produces direct vasodilation due to inhibition of phosphodiesterase; veins less sensitive than arteries to antagonism therefore postural hypotension not usually a problem; reflex tachycardia occurs, but not enhanced by NE release; administered orally; used in management of HTN.

Question 39

Propanolol

Answer 39

a nonselective beta-adrenergic receptor antagonist; used to tx hypertension (slow acting), migraines, tremors, and arrhythmia. Decreases HR/CO/conduction velocity/automaticity; decreases total coronary blood flow and O2 consumption (used to tx angina); decreased CO –> decreased sodium excretion; see increased airway resistance due to Beta-2 blockade; decreased hepatic glycogenolysis and lipolysis;

PK: 100% absorbed from GI tract with large fraction extracted from liver; variable rate of hepatic metabolism; 90% bound to plasma protein; half-life of 3 hrs (prolonged with higher doses);

AE: heart failure (in patients with compromised myocardial fxn); rapid withdrawal –> hypersensitivity to beta-agonists –> angina, arrhythmias, MI; increase airway resistance; insulin-augmented hypoglycemia; cold extremities; fatigue/depression.

Question 40

Reserpine

Answer 40

Depletes catecholamine (NE/Epi) stores indirectly by blocking NE uptake into vesicles (allowing intraneuronal degradation by MAO); see transient sympathomimetic effects with large doses; side effects include sedation and psychic depression.

Question 41

Salmeterol

Answer 41

Beta-2 agonist; promotes relaxation of bronchial and uterine smooth muscle; used to tx asthma, bronchospasms and emphysema; side effects include cardiac/CNS stimulation (due to some Beta 1 stimulation).

Question 42

Terbutaline

Answer 42

Beta-2 agonist; promotes relaxation of bronchial and uterine smooth muscle; used to tx asthma, bronchospasms, emphysema, and delay PTL; side effects include cardiac/CNS stimulation (due to some Beta 1 stimulation).