2 Autonomic Drugs

Question 1

parasympathetic outflow

• preganglionic axon type?
• preganglionic NT released?
• postganglionic axon type?
• postganglionic NT released?

Answer 1

• cholinergic
• ACh
• cholinergic
• ACh

Question 2

sympathetic outflow

• preganglionic axon type?
• preganglionic NT released?
• postganglionic axon type?
• postganglionic NT released?

Answer 2

• cholinergic
• ACh
• adrenergic
• NE

Question 3

what’s the organization of parasympathomimetic drugs?

Answer 3

• cholinergic receptor agonists
• • direct-acting
• • indirect-acting
• – anticholinesterases (reversible)
• – anticholinesterases (irreversible)

Question 4

what’s the organization of direct-acting cholinergic receptor agonists?

Answer 4

• muscarinic receptor agonists

Question 5

what’s the organization of indirect-acting cholinomimetic receptor agonists?

Answer 5

• reversible inhibitors
• • quaternary alcohols
• • carbamate esters
• irreversible inhibitors

Question 6

• (direct-acting cholinomimetic drug) muscarinic receptor agonist MOA
• 2 drug examples

Answer 6

• mimics ACh at junctions of PNS
• eg. bethanechol - resistant to cholinesterases = persistent
• eg. pilocarpine - resistant to cholinesterases, CNS disturbances, sweating, salivation

Question 7

• indirect-acting cholinomimetic drug characteristics and MOA?

Answer 7

• anticholinesterase drugs - inhibit ACh metabolism

- MOA - blocks hydrolysis of ACh, increases ACh in synpase = muscarinic or nicotinic effects

Question 8

• (indirect-acting cholinomimetic drug) - reversible inhibitor - quaternary alcohol MOA
• 1 drug example

Answer 8

• binds reversibly to active site of cholinesterase
• prevents access by ACh - 10-20 min
• eg. edrophnium

Question 9

• (indirect-acting cholinomimetic drug) - reversible inhibitor - carbamate esters MOA
• 2 drug examples

Answer 9

• bind to carbamylate active site of cholinesterase
• more resistant to hydration - 30-120 min
• eg. neostigmine - blurred vision, headache, bradycardia
• eg. physostigmine - lipid soluble, enters CNS = convulsions

Question 10

• irreversible inhibitors MOA

- 1 drug example

Answer 10

• phosphorylates cholinesterase, enzyme inactivated
• resynthesis of enzyme needed for recovery
• miotic agent for glaucoma
• causes intense, prolonged miosis

Question 11

primary target organs of parasympathomimetic drugs

Answer 11

• eye
• NM junctions
• GI and urinary tracts
• respiratory tract
• heart

Question 12

major uses of parasympathomimetic drugs

Answer 12

• glaucoma
• myasthenia gravis
• increase GI and GU motility
• reversal of NM blockade
• atropine poisoning

Question 13

what’re 3 objectives of treating glaucoma?

Answer 13

• decrease IOP
• increase AH outflow
• decrease AH production

Question 14

how do you treat glaucoma?

Answer 14

• muscarinic cholinomimetics contracts ciliary m. and opens drainage angle
• • direct-acting: pilocarpine
• • indirect-acting: physostigmine, isofluorophate
• a adrenoceptor agonists (eg. epinephrine)
• • dilates iris
• • increases AH outflow
• • decreases AH secretion (ciliary epithelium)
• b adrenoceptor blockers (eg. timolol)
• • decreases AH production (ciliary epithelium)

Question 15

how are reversible inhibitors used in

• myasthenia gravis
• reversal of NM blockade
• GI and GU
• cardiovascular

Answer 15

• neostigmine increases strength of contraction
• cholinesterase inhibitors increase amount of ACh, competes with NM blocker for nicotinic receptors
• stimulates peristalsis and bladder contraction
• decreases HR, contractility, CO

Question 16

where are 3 places that cholinergic receptor antagonists block actions of ACh?

Answer 16

• central and peripheral muscarinic receptors
• nicotinic receptors at NM junction
• nicotinic receptors in ganglia

Question 17

2 drugs that are muscarinic blockers

Answer 17

atropine

tropicamide

Question 18

1 drug that’s a neuromuscular blocker (antinicotinic)

Answer 18

curare

Question 19

MOA of muscarinic blocking drugs

Answer 19

• reversible blockade of ACh at M receptors by competitive binding
• reverse by increasing ACh or agonist to decrease blockade

Question 20

atropine (M blocking prototype) characteristics

Answer 20

• lipid soluble, enters CNS
• effect lasts longer than tropicamide
• blocks all parasympathetic functions
• • decreased sweating, decreased salivation
• • rapid heart rate, dilation, blurred vision
• • hallucination delirium, coma
• • toxicity tx: physostigmine

Question 21

ophthalmic uses of antimuscarinics (eg. atropine, tropicamide)?

Answer 21

• mydriasis and
  cycloplegia
  – measure ref errors without accommodation
  – retinal exam

Question 22

describe adrenergic receptor agonists

Answer 22

• they’re sympathomimetic drugs
• mimic actions of NE and EP
• profound effects on heart and peripheral circulation
• undesirable side effects

Question 23

cardiovascular action of adrenergic agonists?

Answer 23

• alter rate and force of heart contractions
• alter tone of bvs
• influences BP since BP = CO x PVR

Question 24

organization of adrenergic receptor agonists - drugs increase sympathetic activity

Answer 24

• direct acting
• • a agonists
• – non-selective
• – selective a1
• • b agonists
• – non-selective
• – selective b1 or b2
• indirect-acting
• • releasers
• • reuptake inhibitors

Question 25

4 effects of direct-acting, non-selective adrenergic receptor agonists (eg. epinephrine)

Answer 25

- cardiac - b1 activation --> increases CO and increases force/rate of contraction - vascular smooth muscle - a1 stimulation --> vasoconstriction in skin/kidneys --> increases PVR - smooth muscle - - a1 stimulation --> contraction of spleen, bladder sphincter, dilator - - b2 stimulation --> bronchodilation, decreases GI contractions, decreases tone/contraction of pregnant uterus, relaxes urinary bladder - metabolic - increases circulating glucose, lactic acid, free fatty acids

Question 26

effects of direct-acting, selective adrenergic receptor a agonists for phenylephrine and clonidine

Answer 26

- phenylephrine - a1 agonist, vasoconstriction, increases BP, pupillary dilation - clonidine - a2 adrenoceptor agonist in brain stem, decreases sympathetic outflow, decreases BP

Question 27

effects of direct-acting, selective adrenergic receptor b agonists for dopamine/dobutamine and albuterol

Answer 27

- dopamine/dobutamine - b1 receptor agonist, increases contractility, stimulates hearts, dilates renal vasculature, increases GFR (used in renal failure) - albuterol - b2 agonist, dilator (used in asthma), no stimulation of heart, short duration

Question 28

effects of indirect-acting, selective adrenergic receptor b agonists for pseudephedrine and amphetamine

Answer 28

- pseudephedrine (Benadryl-D, Sudafed) - stimulates NE release, hay fever release - amphetaine - facilitates release and blocks reuptake of NE and dopamine (cocaine only block reuptake), central and peripheral sympathomimetic effects

Question 29

cardiovascular system applications of adrenergic agonists

Answer 29

- hypotension/shock - tx: fluids, a1 agonists eg. phenylephrine - cardiac insufficiency - b agonist eg. epinephrine, dobutamine, dopamine - local vasoconstriction - lidocaine HCl with epinephrine -

Question 30

respiratory applications of adrenergic agonists

Answer 30

- asthma - b2 activation for bronchodilation eg. albuterol

Question 31

mucous membrane congestion applications of adrenergic agonists

Answer 31

- hay fever/colds - a receptor activation for decongestion eg. phenylephrine, pseudephedrine

Question 32

anaphylaxis applications of adrenergic agonists

Answer 32

tx: epinehphrine

Question 33

ophthalmology applications of adrenergic agonists

Answer 33

- a1 activation, mydriasis, decrease synechiae

Question 34

organization of adrenergic receptor antagonists - drugs decrease sympathetic activity

Answer 34

- direct acting - - a blockers - -- non-selective - -- selective a1 or a2 - - b blockers - -- non-selective - -- selective b1 or b2

Question 35

a receptor blocking drugs MOA

Answer 35

- a1 blockade --> vasodilation --> decreases peripheral resistance and BP - non-selective (eg. phentolamine) - competitive reversible non-selective a1&2 blocker for pheochromocytoma - selective (eg. prazosin) - a1 blockage --> dilation of arterial and venous smooth muscle for chronic hypertension --> dizziness/headache

Question 36

b receptor blocking drugs MOA

Answer 36

- drugs with higher affinity for b1 are more important clinically - low bioavailability - for cardiovascular and ophthalmic applications - AE - decreased drug elimination with liver disease, decreased blood flow to liver, inhibition of liver enzymes

Question 37

2 non-selective b adrenergic blockers

Answer 37

- propranolol - reversible b1&2 R antagonist, -ve chronotrope (decrease heart rate) and inotrope (decrease force of muscular contractions) - - for cardiovascular diseases - - AE due to b2 blockade - -- worsens asthma by increasing airway resistance - -- worsens HF by decreasing cardiac contractility - -- hypoglycemia after insulin in diabetics - timolol - decreases IOP in glaucoma decreases AH production

Question 38

1 selective b1 adrenergic blocker

Answer 38

- metoprolol - -ve chronotrope and inotrope, used in hypertension, safe for asthmatics

Question 39

3 therapeutic applications of b blockers

Answer 39

- hypertension - decreases BP due to effects on heart (-ve inotrope and chronotrope) - ischemic heart disease - decreases angina, increases exercise tolerance, decreases HR, decreases oxygen demand - cardiac arrhythmias due to b1 blockade - decreases rate of SA discharge, decreases AV conduction, decreases ventricular response to atrial arrhythmias