2 Autonomic Drugs Flashcards
parasympathetic outflow
- preganglionic axon type?
- preganglionic NT released?
- postganglionic axon type?
- postganglionic NT released?
- cholinergic
- ACh
- cholinergic
- ACh
sympathetic outflow
- preganglionic axon type?
- preganglionic NT released?
- postganglionic axon type?
- postganglionic NT released?
- cholinergic
- ACh
- adrenergic
- NE
what’s the organization of parasympathomimetic drugs?
- cholinergic receptor agonists
- direct-acting
- indirect-acting
- – anticholinesterases (reversible)
- – anticholinesterases (irreversible)
what’s the organization of direct-acting cholinergic receptor agonists?
- muscarinic receptor agonists
what’s the organization of indirect-acting cholinomimetic receptor agonists?
- reversible inhibitors
- quaternary alcohols
- carbamate esters
- irreversible inhibitors
- (direct-acting cholinomimetic drug) muscarinic receptor agonist MOA
- 2 drug examples
- mimics ACh at junctions of PNS
- eg. bethanechol - resistant to cholinesterases = persistent
- eg. pilocarpine - resistant to cholinesterases, CNS disturbances, sweating, salivation
- indirect-acting cholinomimetic drug characteristics and MOA?
- anticholinesterase drugs - inhibit ACh metabolism
- MOA - blocks hydrolysis of ACh, increases ACh in synpase = muscarinic or nicotinic effects
- (indirect-acting cholinomimetic drug) - reversible inhibitor - quaternary alcohol MOA
- 1 drug example
- binds reversibly to active site of cholinesterase
- prevents access by ACh - 10-20 min
- eg. edrophnium
- (indirect-acting cholinomimetic drug) - reversible inhibitor - carbamate esters MOA
- 2 drug examples
- 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
- irreversible inhibitors MOA
- 1 drug example
- phosphorylates cholinesterase, enzyme inactivated
- resynthesis of enzyme needed for recovery
- miotic agent for glaucoma
- causes intense, prolonged miosis
primary target organs of parasympathomimetic drugs
- eye
- NM junctions
- GI and urinary tracts
- respiratory tract
- heart
major uses of parasympathomimetic drugs
- glaucoma
- myasthenia gravis
- increase GI and GU motility
- reversal of NM blockade
- atropine poisoning
what’re 3 objectives of treating glaucoma?
- decrease IOP
- increase AH outflow
- decrease AH production
how do you treat glaucoma?
- 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)
how are reversible inhibitors used in
- myasthenia gravis
- reversal of NM blockade
- GI and GU
- cardiovascular
- 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
where are 3 places that cholinergic receptor antagonists block actions of ACh?
- central and peripheral muscarinic receptors
- nicotinic receptors at NM junction
- nicotinic receptors in ganglia
2 drugs that are muscarinic blockers
atropine
tropicamide
1 drug that’s a neuromuscular blocker (antinicotinic)
curare
MOA of muscarinic blocking drugs
- reversible blockade of ACh at M receptors by competitive binding
- reverse by increasing ACh or agonist to decrease blockade
atropine (M blocking prototype) characteristics
- 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
ophthalmic uses of antimuscarinics (eg. atropine, tropicamide)?
- mydriasis and
cycloplegia
– measure ref errors without accommodation
– retinal exam
describe adrenergic receptor agonists
- they’re sympathomimetic drugs
- mimic actions of NE and EP
- profound effects on heart and peripheral circulation
- undesirable side effects
cardiovascular action of adrenergic agonists?
- alter rate and force of heart contractions
- alter tone of bvs
- influences BP since BP = CO x PVR
organization of adrenergic receptor agonists - drugs increase sympathetic activity
- direct acting
- a agonists
- – non-selective
- – selective a1
- b agonists
- – non-selective
- – selective b1 or b2
- indirect-acting
- releasers
- reuptake inhibitors
4 effects of direct-acting, non-selective adrenergic receptor agonists (eg. epinephrine)
- 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
effects of direct-acting, selective adrenergic receptor a agonists for phenylephrine and clonidine
- phenylephrine - a1 agonist, vasoconstriction, increases BP, pupillary dilation
- clonidine - a2 adrenoceptor agonist in brain stem, decreases sympathetic outflow, decreases BP
effects of direct-acting, selective adrenergic receptor b agonists for dopamine/dobutamine and albuterol
- 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
effects of indirect-acting, selective adrenergic receptor b agonists for pseudephedrine and amphetamine
- 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
cardiovascular system applications of adrenergic agonists
- hypotension/shock - tx: fluids, a1 agonists eg. phenylephrine
- cardiac insufficiency - b agonist eg. epinephrine, dobutamine, dopamine
- ## local vasoconstriction - lidocaine HCl with epinephrine
respiratory applications of adrenergic agonists
- asthma - b2 activation for bronchodilation eg. albuterol
mucous membrane congestion applications of adrenergic agonists
- hay fever/colds - a receptor activation for decongestion eg. phenylephrine, pseudephedrine
anaphylaxis applications of adrenergic agonists
tx: epinehphrine
ophthalmology applications of adrenergic agonists
- a1 activation, mydriasis, decrease synechiae
organization of adrenergic receptor antagonists - drugs decrease sympathetic activity
- direct acting
- a blockers
- – non-selective
- – selective a1 or a2
- b blockers
- – non-selective
- – selective b1 or b2
a receptor blocking drugs MOA
- 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
b receptor blocking drugs MOA
- 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
2 non-selective b adrenergic blockers
- 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
1 selective b1 adrenergic blocker
- metoprolol - -ve chronotrope and inotrope, used in hypertension, safe for asthmatics
3 therapeutic applications of b blockers
- 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
