Pharmacology: Autonomic Drugs

Question 1

alpha1

Answer 1

G-protein: q
Fcn: ^vascular smooth muscle contraction, ^pupillary dilator muscle contraction (mydriasis), ^intestinal and bladder sphincter muscle contraction

Question 2

alpha2

Answer 2

G-protein: i*inhibitory
Fcn: v-sympathetic (adrenergic) outflow, v-insulin release, v-lipolysis, ^platelet aggregation, v-aqueous humor production

Question 3

beta1

Answer 3

G-protein: s
Fcn: ^HR, ^contractility, ^renin release, ^lipolysis
(#1 in my heart)

Question 4

beta2

Answer 4

G-protein: s
Fcn: vasodilation, bronchodilation, ^lipolysis, ^insulin release, v-uterine tone (tocolysis), ciliary muscle relaxation, ^aqueous humor production

Question 5

beta3

Answer 5

G-protein: s

Fcn: ^lipolysis, ^thermogenesis in skeletal muscle

Question 6

D1

Answer 6

G-protein: s

Fcn: relaxes renal vascular smooth muscle

Question 7

D2

Answer 7

G-protein: i *inhibitory

Fcn: modulates transmitter release, especially in brain

Question 8

G-protein q

Answer 8

Gq –> phospholipase C, which cleaves PIPs –> DAG and IP3. DAG activates PKC. IP3 increases intracellular Ca –> smooth muscle contraction.

Question 9

G-protein s

Answer 9

activates adenylyl cyclase, which causes ATP–>cAMP. cAMP–>PKA–> increases intracellular Ca in heart

Question 10

G-protein i

Answer 10

inhibits adenylyl cyclase; inhibits release of NE and DA

Question 11

Tyramine

Answer 11

Normally degraded by MAO, but if patient on MAO inhibitor, tyramine levels rise (from cheese, wine). Displaces neurotransmitters (NE) from their presynaptic vesicles, meaning there is more NE active –> ^sympathetic stimulation. Classically results in HTN crisis.

Question 12

Albuterol, salmeterol

Answer 12

direct sympathomimetics
b2>b1
Albuterol for acute asthma or COPD
Salmeterol for long-term asthma or COPD control

Question 13

Dobutamine

Answer 13

direct sympathomimetic
b1>b2, a
heart failure (inotropic>chronotropic)
cardiac stress testing

Question 14

Dopamine (DA)

Answer 14

direct sympathomimetic
D1=D2>b>a
unstable bradycardia, heart failure, shock
inotropic and chronotropic effects at lower doses due to b effects; vasoconstriction at high doses due to a effects.

Question 15

Epinephrine (EPI)

Answer 15

direct sympathomimetic
b>a
anaphylaxis, asthma, open-angle glaucoma
a effects predominate at high doses
significantly stronger effect at b2 receptor than norepinephrine

Question 16

Fenoldopam

Answer 16

direct sympathomimetic 
D1
postoperative HTN, HTN crisis, vasodilator (coronary, peripheral, renal, and splanchnic)
promotes natriuresis 
can cause hypotension and tachycardia

Question 17

Isoproterenol

Answer 17

direct sympathomimetic
b1=b2
electrophysiological evaluation of tachyarrhythmias
can worsen ischemia
causes b2-mediated vasodilation –> v-MAP and ^HR through b1 and reflex activity

Question 18

Midodrine

Answer 18

direct sympathomimetic
a1
autonomic insufficiency and postural hypotension
may exacerbate supine HTN

Question 19

Norepinephrine

Answer 19

direct sympathomimetic
a1>a2>ba
hypotension, septic shock
a1-mediated vasoconstriction –> ^systolic and diastolic pressures –> ^MAP –> reflex bradycardia

Question 20

Phenylephrine

Answer 20

direct sympathomimetic
a1>a2
hypotension (vasoconstrictor), ocular procedures (mydriatic), rhinitis (decongestant)

Question 21

Amphetamine

Answer 21

indirect general agonist, reuptake inhibitor, releases stored catecholamines (^NE)
use: narcolepsy, obesity, ADHD

Question 22

Cocaine

Answer 22

indirect general agonist, reuptake inhibitor
causes vasoconstriction and local anesthesia
never give b-blocker if cocaine intoxication suspected (–> unopposed a1 activation and extreme HTN)

Question 23

Ephedrine

Answer 23

indirect general agonist, releases stored catecholamines (^NE)
use: nasal decongestion, urinary incontinence, hypotension

Question 24

Clonidine, guanfacine

Answer 24

sympatholytics
a2-agonists
HTN urgency, ADHD, Tourette syndrome
Adverse effects: CNS depression, bradycardia, hypotension, respiratory depression, miosis

Question 25

a-methyldopa

Answer 25

sympatholytic a2-agonist HTN in pregnancy Adverse effects: direct Coombs positive hemolysis, SLE-like syndrome

Question 26

Phenoxybenzamine

Answer 26

nonselective a-blocker irreversible pheochromocytoma (used preoperatively) to prevent catecholamine (HTN) crisis Adverse effects: orthostatic hypotension, reflex tachycardia

Question 27

Phentolamine

Answer 27

nonselective a-blocker reversible give to patients on MAO inhibitors who eat tyramine-containing foods Adverse effects: orthostatic hypotension, reflex tachycardia

Question 28

Prasozin, terazosin, doxazosin, tamsulosin (-osin!)

Answer 28

``` a1-selective blocker urinary symptoms of BPH prazosin - PTSD HTN (except tamsulosin) Adverse effects: 1st-dose orthostatic hypotension, dizziness, headache ```

Question 29

Mirtazapine

Answer 29

a2-selective blocker depression Adverse effects: sedation, ^serum cholesterol, ^appetite

Question 30

b-blocker applications and actions

Answer 30

Angina pectoris - v HR and contractility, resulting in v O2 consumption MI - v mortality SVT - metoprolol, esmolol - v AV conduction velocity HTN - v CO, v renin secretion (due to b1-receptor blockade on JGA cells) HF - bisoprolol, carvedilol, metoprolol - v mortality Glaucoma - timolol - v secretion of aqueous humor Variceal bleeding - nadolol, propanolol - v hepatic venous pressure gradient and portal HTN

Question 31

b-blocker adverse effects

Answer 31

Erectile dysfunction Cardiovascular - bradycardia, AV block, HF CNS - seizures, sedation, sleep alterations Dyslipidemia (metoprolol) Asthma/COPD exacerbations Risk of unopposed a-adrenergic receptor agonist activity in cocaine users

Question 32

b1-selective antagonists

Answer 32

A-M 1st half alphabet | acebutolol (partial agonist), atenolol, betaxolol, esmolol, metoprolol

Question 33

nonselective b antagonists

Answer 33

N-Z 2nd half alphabet | nadolol, pindolol (partial agonist), propranolol, timolol

Question 34

nonselective a and b-antagonists

Answer 34

carvedilol, labetalol

Question 35

Nebivolol

Answer 35

combines cardiac-selective b1-adrenergic blockade with stimulation of b3-receptors, which activate NO synthase in the vasculature

Question 36

M1

Answer 36

Parasympathetic receptor G-protein q CNS, enteric nervous system

Question 37

M2

Answer 37

Parasympathetic receptor G-protein i (*inhibitory) v HR and contractility of atria

Question 38

M3

Answer 38

Parasympathetic receptor G-protein q ^ exocrine gland secretions (lacrimal, sweat, salivary, gastric acid), ^ gut peristalsis, ^ bladder control, bronchoconstriction, ^ pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation), vasodilation (NO release in vascular smooth muscle endothelial cells)

Question 39

Bethanechol

Answer 39

ACh/muscarinic/cholinomimetic agonist Activates Bowel and Bladder smooth muscle resistant to AChE Used: postoperative ileum, neurogenic ileum, urinary retention

Question 40

Carbachol

Answer 40

muscarinic and nicotinic agonist CARBon copy of AcetylCHOLine Constricts pupil and relieves intraocular pressure in open-angle glaucoma

Question 41

Methacholine

Answer 41

muscarinic agonist Stimulates muscarinic receptors in airway when inhaled Challenge test for diagnosis of asthma

Question 42

Pilocarpine

Answer 42

muscarinic agonist Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma) Resistant to AChE Potent stimulator of sweat, tears, and saliva Xerostomia (Sjogren Syndrome)

Question 43

Atropine

Answer 43

Muscarinic antagonist Treats bradycardia and ophthalmic applications Blocks cholinesterase inhibitor poisoning ^pupil dilation, cycloplegia v airway secretions v stomach acid secretions v gut motility v bladder urgency in cystic Adverse effects: Hot as hare, dry as bone, red as beet, blind as bat, mad as hatter; constipation, rapid pulse, glaucoma in elderly, urinary retention in men with prostatic hyperplasia, hyperthermia in infants

Question 44

Benztropine

Answer 44

Muscarinic antagonist CNS Use: Parkinson's disease, acute dystonia

Question 45

Ipratropium, tiotropium

Answer 45

Muscarinic antagonist | Use: COPD, asthma

Question 46

Scopolamine

Answer 46

Muscarinic antagonist CNS Use: motion sickness

Question 47

Muscarinic agonists

Answer 47

v HR (reflex tachycardia due to vBP) v tone in arterioles and small blood vessels (due to NO release) --> v TPR and v BP other smooth muscle ^tone and contraction ^salivation and mucous secretions pupil constriction (miosis) ^ tone GI tract, contractions, peristalsis bronchoconstriction v bladder capacity