Autonomic Drugs Overview Flashcards
Direct acting cholinergic drugs are either ____ or ____
muscarinic agonist or nicotinic agonist
muscarinic agonists include
acetylcholine, muscarine, pilocarpine, bethanechol
nicotinic agonists include
acetylcholine, nicotine, succinylcholine, varenicline
indirect acting cholinergic drugs are either ____ or ____
AChE Inhibitors that are reversible or irreversible
reversible AChE inhibitors include
edrophonium, neostigmine, pyridostigmine, physostigmine, donepezil
irreversible AChE inhibitors include
echothiophate
organophosphate insecticides
Sarin nerve gases
is edrophonium long, intermediate, or short acting?
short
is neostigmine long, intermediate, or short acting?
intermediate
Acetylcholine
quaternary ammonium
short duration
has nicotinic and muscarinic activity
MOA AChE inhibitors (indirect)
bind to active site and inhibit AChE
prevents ACh from binding so increases the ACh concentration, t 1/2, and activity
is edrophonium an alcohol or carbamate?
alcohol
is neostigmine an alcohol or carbamate?
carbamate
Clinical uses for AChE inhibitors
reverseal of NM blockade by nondepolarizing drugs, myasthenia gravis diagnosis and treatment, glaucoma, ileus, postop urinary retention, Alzheimer’s
AChE inhibitors effects
autonomic nervous system = increased secretions, increased GI motility, bronchoconstriction, bradycardia, hypotension, miosis
AChE inhibitors adverse effects
if given in large doses = depolarizing block
toxicity = excitation (convulsion) then depression (unconscious)
which reversible AChE inhibitors are quarternary amines and what is the significance of that?
edrophonium and neostigmine
polar = don’t cross BBB
which reversible AChE inhibitors are tertiary amines and what is the significance of that?
physostigmine
nonpolar = crosses BBB
onset and DOA for edrophonium
onset: 30-60 seconds
DOA: 10 minutes
onset and DOA for neostigmine
onset: 10 -30 minutes
DOA: 2- 4 hours
onset and DOA for physostigmine
onset: 3- 8 minutes
DOA: 1 hour
Cholinergic crisis toxicity mnemonic
DUMBBELLS D - diarrhea, diaphoresis U- urination M - miosis B - bradycardia B- bronchoconstriction E - excitation, emesis L - lacrimation S - salivation, sweating
What is the antidote for muscarinic toxicity?
atropine
What is the antidote for AChE Inhibitor toxicity?
atropine or pralidoxime (have to give early)
which muscarinic agonist is typically used for treatment of bladder and GI hypotonia?
betanechol (stimulates motility)
what do muscarine, pilocarpine, oxotremorine, and cevimeline have in common?
muscarinic receptor specificity
muscarinic agonist effects (parasympathomimetic)
decrease HR, CO, and arterial pressure vasodilation via nitric oxide increase GI motility contracts bladder bronchoconstriction increase secretions miosis, decrease intraocular pressure
clinical uses for muscarinic agonists
glaucoma, ileus, urinary retention, xerostomia (Dry mouth)
mnemonic for muscarinic agonist GI/GU effects
SLUDGE s- salivation l - lacrimation u - urination d - diarrhea g - GI upset e - emesis
nicotinic nerve agonists effects
stimulation of post ganglionic neuronal activity, CNS stimulation
nicotinic nerve agonists clinical use
smoking cessation
nicotinic nerve agonists adverse effects
CNS stimulation, skeletal muscle depolarization/blockade, HTN, increase HR, N/V/D
nicotinic muscle agonist effects
activation of NM endplates, contraction
nicotinic muscle agonist clinical uses
depolarizing skeletal muscle paralysis
anticholinergics are either ____ or _____
muscarinic antagonist or nicotinic antagonist
nonselective muscarinic antagonist examples
atropine, glycopyrrolate, scopolamine
nicotinic nerve ganglionic blocker example
hexamethonium (historical)
nicotinic muscle NM blocker examples
atracurium, cisatracurium, vecuronium, rocuronium, pancuronium
muscarinic antagonist effects
increase HR, bronchodilation, decreased GI/GU, decrease glands/secretions, decrease sweating, mydriasis, sedation
would you expect effects at the blood vessels with muscarinic antaognists?
no
would you expect effects at the skeletal muscle with muscarinic antagonists?
no
clinical uses of muscarinic antagonists
motion sickness, parkinson’s, COPD, asthma, excessive secretions, GI hypermotility, urinary urgency, bradycardia
which muscarinic antagonists are tertiary amines and what is the significance of that?
atropine and scopolamine
crosses BBB
half life of atropine
about 4 hours
in elderly - 10 hours
eye effects may last days
half life, onset, DOA of scopolamine
1-4 hours (IV), onset 10 minutes, DOA 2 hours (IV)
glycopyrrolate half life, onset, DOA
1 hour, onset 1 minute, DOA 7 hours
memory aid for anticholinergic effects
Dry as a bone, hot as a pistol, red as a beet, blind as a bat, mad as a hatter
medication classes with anticholinergic activity
antihistamines, antispasmodics, antiparkinson drugs, skeletal muscle relaxants, antipsychotics, antidepressants, antimuscarinics for urinary incontinence
which patient population is especially susceptible to anticholinergic toxicity
elderly
nicotinic muscle antagonists effects and clinical uses
effects: competitive antagonism at skeletal muscle, non depolarizing
uses: skeletal muscle relaxation for surgical, intubation, and ventilation control
nicotonic nerve antagonist effects and uses
effects: blocks ganglionic output
uses: historical, hypertensive emergency
direct acting adrenergic agonists include
alpha agonists, beta agonists, mixed alpha and beta agonists
indirect acting adrenergic agonists include
NT releasers, NE reuptake inhibitors, MAO inhibitors
nonselective alpha agonist
norepinephrine
alpha 1 agonist
phenylephrine
alpha 2 agonist
clonidine, dexmedetomidine
nonselective beta agonist
isoproterenol
beta 1 agonist
dobutamine
beta 2 agonist
albuterol
mixed alpha/beta agonist
epinephrine, norepinephrine
epinephrine receptors
alpha 1 and 2, beta 1 and 2
norepinephrine receptors
alpha 1 and 2 and beta 1
neurotransmitter releasers
amphetamine and ephedrine
norepi reuptake inhibitors
cocaine, SNRI
MAO inhibitors
tranylcypromine, selegiline
dopamine receptors
alpha 1, beta 1, dopamine 1 and 2
endogenous catecholamines
dopamine, epi, norepi
why don’t we give catecholamines PO?
they are polar, poor CNS penetration
ephedrine, pseudoephedrine
displaces/releases stored catecholamine NT
some agonist activity
amphetamine
displaces/releases stored catecholamine NT, inhibits catecholamine reuptake
cocaine
blocks NE reuptake, blocks sodium channels
tyramine
displaces/releases stored catecholamines
in fermented foods and interact with MAOIs (HTN crisis)
alpha 1 agonist effects
vasoconstriction
smooth muscle contracts expect in GI
GI/GU sphincters contract
mydriasis
alpha 2 agonist effects
decreases NE release, inhibit sympathetic outflow
platelet aggregation, decrease insulin
beta 1 agonist effects
increase HR and contractility
increase renin release
trophic effect
beta 2 agonist effects
bronchodilation, vasodilation, most smooth muscle relaxes, tremors, GI/GU relax, glycogenolysis
low dose epinephrine
beta effects
high dose epinephrine
alpha effects
epinephrine effects with local anesthetics
causes vasoconstriction to keep LA in the desired area and prevent systemic effects
low dose dopamine
Dopamine 1 in renal, mesenteric, coronary vascular beds
medium dose dopamine
Beta 1
high dose dopamine
alpha 1
which drug has the highest affinity for alpha receptors?
epinephrine
which drug has the highest affinity for beta receptors?
isoproterenol
nonselective alpha adrenergic blocker
phenoxybenzamine
phentolamine
alpha 1 adrenergic blocker
prazosin
alpha 2 adrenergic blocker
yohimbine
nonselective beta blocker
propranolol
beta 1 blocker
metoprolol
esmolol
why don’t we have beta 2 blockers?
would cause bronchoconstriction (no real good reason to do that)
a beta 2 receptor agonist would NOT
stimulate renin release
beta 1
the effects of isoproterenol could be blocked by a
nonselective beta adrenergic receptor antagonist
what would be expected upon administration of a muscarinic agonist drug, but NOT with parasympathetic nerve stimulation?
vasodilation
cholinergic receptors would be found at all of the following sites except
juxtaglomerular cells
