Autonomic Drugs Lecture 2 Flashcards
Cholinergic drugs can be either
direct-acting (receptor agonists) or indirect acting (ACHe-inhibitors)
Direct-acting receptor agonists include
muscarinic agonist such as acetylcholine, pilocarpine or nicotinic agonist such as succinylcholine or varenicline
Indirect-acting receptor agonists include
reversible acetylcholinesterase inhibitors (Edrophonium, neostigmine) and irreversible acetylcholinesterase inhibitors (nerve gases)
Acetylcholinesterase inhibitor drugs mechanism of action
binding to active site and inhibiting acetylcholinesterase
undergoes hydrolysis; acidic portion slowly released, prevents acetylcholine from binding which increases the ACh concentration
Irreversible vs. reversible AChE inhibitors
Irreversible means requires synthesis of new AChE to overcome
Reversible includes short & medium duration and it latches on, slowly hydrolyzes and moves acetylcholinesterase
Clinical uses of acetylcholinesterase inhibitors include
reversal of NM blockade by non-depolarizing drug myasthenia gravis tx & diagnosis glaucoma GI-ileus postop urinary retention Alzheimer's disease non-therapeutic-insecticide
Effect of acetylcholinesterase inhibitor
increases acetylcholine
amplifies effects @ cholinergic synapses; indirect stimulant of nicotinic and muscarinic receptors by increased acetylcholine
Cholinergic crisis
DUMBELSS: Diarrhea, diaphoresis, urination, miosis, bradycardia, excitation (CNS; skel musc) ((paralysis follows initial excitation)), Lacrimation, Salivation, Sweating
Edrophonium is considered to be a
acetylcholinesterase inhibitor, alcohol, quaternary amine
Edrophonium works by
causing a reversible blockade of acetylcholinesterase
Edrophonium onset & duration
onset: 30-60 seconds
duration: 10 minutes
Edrophonium is used to
reverse nondepolarizing NM block
Neostigmine is considered to be a
acetylcholinesterase inhibitor, carbamate, quaternary amine
Neostigmine works by
hydrolyzed by acetylcholinesterase
Neostigmine is used for
reversal of NDMB
Neostigmine onset & duration
Onset: 10-30 minutes
Duration: 2-4 hours
Physostigmine is considered to be
a acetylcholinesterase inhibitor, carbamate, tertiary amine (crosses BBB)
Physostigmine works by
hydrolyzing acetylcholinesterase
Physostigmine is used for
treatment of anticholinergic toxicity
Physostigmine onset & duration
onset: 3-8 min.
duration: 1 hr.
AChE inhibitor drug effects autonomic
increased secretions (salivary, lacrimal, bronchial, GI), increased GI motility, bronchoconstriction, bradycardia, hypotension, miosis
AChE inhibitor drug affects NMJ
reverses NM block by non-depolarizing blocker, improves transmission-myasthenia gravis, large doses-depolarizing block
AChE inhibitor drug affects CNS
therapeutic- dementia Tx
toxicity- excitation (possibly convulsions) and then depression (unconscious)
The antidote for cholinergic toxicity includes
atropine
Pralidoxime can be given to
regenerate active AChE enzyme (helpful in cholinergic toxicity)
Muscarinic agonist drug effects are known as
“parasympathomimetic”
Muscarinic agonist drug effects include
CV: decreased HR, decreased CO & arterial pressure, vasodilation
GI: increased motility
Bladder: contracts
Lungs: bronchoconstriction
Secretions: increased sweat, lacrimation, salivation, bronchial
Eyes: miosis, accommodation for near vision, decreased intraocular pressure
Muscarinic agonist clinical uses include
Glaucoma, contract ciliary body & increase outflow of aqeous humor
GU/GI: postop ileus, postop urinary retention, xerostomia
What is the effect of muscarinic agonists on vascular smooth muscle
vasodilation via nitrous oxide
Muscarinic agonists include
acetylcholine, muscarine, pilocarpine, bethanechol
The “SLUDGE” mnemonic applies to
muscarinic agonists and includes salivation, lacrimation, urination, diarrhea, GI upset, and emesis
What drug is a nicotinic agonists?
succinylcholine
What drugs are nicotinic antagonists?
pancuronium, vecuronium, atracurium, cisatricurium, rocuronium
Nicotinic N receptor agonists uses include
smoking cessation
Nicotinic N agonists effects include
stimulation of post-ganglionic neuronal activity (autonomic NS) and CNS stimulation
Nicotinic N agonists adverse effects include
CNS stimulation (excitatory), Skeletal muscle depolarizing/blockade, HTN, increased HR, N/V, diarrhea
Nicotinic M agonists effects include
Activation of NM endplates
contraction
Nicotinic M agonists clinical uses include
depolarizing skeletal muscle paralysis
Nicotinic M agonists adverse include
paralysis
Cholinergic drugs should not be given in patients with
GI/GU obstruction, CV disease, Respiratory disorder (COPD, asthma)
Nonselective muscarinic antagonists include
atropine, glycopyrrolate, scopolamine
Clinical uses of muscarinic receptor antagonists include
motion sickness (scopolamine), Parkinson’s, exam requiring eyes, decreases secretions, COPD, asthma, GI hypermotility, urinary urgency, anesthetic premed to decrease secretions and for sedation, cholinergic poisoning, AChE inhibitor toxicity
The effects of muscarinic receptor antagonists include
increased heart rate, bronchodilation, decreased GI, GU & Glands; decreased sweat glands, mydriasis, sedation
Would you expect to see effects of muscarinic receptor antagonists at blood vessels & skeletal muscle?
No b/c there is only nicotinic receptors present in these areas
Medication classes with anticholinergic activity include
antihistamines, antispasmodics, antiparkinson drugs, skeletal muscle relaxants, antipsychotics, antidepressants, antimuscarinics for urinary incontinence
Who is most susceptible to anticholinergic toxicity?
elderly
Potential concerns with anti-muscarinic drugs include
hyperthermia risk d/t decreased sweating, glaucoma, GU obstruction, prostatic hypertrophy, GI-ileus, ulcerative colitis, etc., CV especially MI, HF, arrhythmias, HTN
Memory aid for anticholinergic effects is:
dry as a bone, hot as a pistol, red as a beet, blind as a bat, mad as a hatter
The drug class of atropine is
muscarinic antagonists & it crosses BBB
The drug class of scopolamine is
muscarinic antagonists and it crosses BBB causing CNS effects of amnesia & sedation
The drug class of glycopyrrolate is
muscarinic antagonists and it has decreased CNS effects
The half-life of atropine is
4 hours (elderly ~10 hours)
Atropine can be administered
IV, IM, Ophthalmic
Atropine is used for
ophthalmic, bradycardias, preop, inhibit secretions, adjunct to NM block reversal
Scopolamine half life, onset & duration is
half-life: 1-4 hours
onset: 10 min.
duration: 2 hours
Scopolamine can be administered
transdermal patch, IV, or IM
Scopolamine uses include
motion sickness, postop N/V, preop for amnesia, sedation, anti-emetic, decreasing secretions
Glycopyrrolate half-life, onset, and duration includ
half-life: 1 hour
Onset: 1 min
Duration: 7 hour
Glycopyrrolate is used for
pre-op; cardiac dysrhythmia (vagal reflex association), adjunct- reversal NM blockade
The mechanism of action for NM blocker competitive agonists is
binding to nicotinic receptor at NMJ and preventing acetylcholine from thus binding
What are the effects of nicotinic M receptor antagonists?
competitive antagonism at skeletal muscle
non-depolarizing
The clinical uses of nicotinic M receptor antagonists include:
skeletal muscle relaxation for surgical intubation, ventilation control
What drugs are able to counteract a nicotinic M receptor antagonist neuromuscular blockade?
acetylcholinesterase inhibitors
What are the effects of nicotinic N receptor antagonists?
it blocks ganglionic output
What are the clinical uses of nicotinic N receptor antagonists?
Historically used for hypertensive emergency
Adrenergic agonists may also be called
sympathomimetics
Direct acting adrenergic agonists can act on
alpha, beta or mixed alpha/beta
Indirect acting adrenergic agonists work by
increasing NT release, inhibiting NE reuptake, or decreasing metabolism of NT (MAO inhibitor)
Adrenergic drug types can include
indirect, direct receptor agonist and mixed-multiple sites of action
mixed work by release NE from nerve terminal and activate adrenergic receptors
Tyramine works by
displacing/releasing stored catecholamines
not a drug, in fermented foods; role in drug-food interactions of MAO inhibitors
Cocaine works by
blocks NE reuptake; blocks sodium channels so has local anesthetic actions
Amphetamine works by
displaces/releases stored catecholamines NT
secondary inhibits catecholamine reuptake
Amphetamine is used in
ADHD, narcolepsy, & appetite suppression
Indirect acting adrenergic agonists include
amphetamine, cocaine, SNRI, tranylcypromine
ephedrine is mixed
Ephedrine & pseudoephedrine are (class & MOA)
indirect acting mixed adrenergic agonists and work by displacing/releasing stored catecholamine NT, have some agonists activity on alpha and beta adrenergic receptors
What herbal source contains ephedrine?
ma huang
When catecholamines are administered as drugs:
rapid onset, brief duration, don’t give PO (b/c won’t cross) and have poor CNS penetration for the same reason
Most adrenergic drugs are
non-catecholamines, longer acting, and have PO administration
Receptor affinity of Epi. vs. Norepi. vs. Isoproterenol for alpha adrenoreceptors:
High to low: epi, norepi, isoproterenol
Receptor affinity of Epi. vs. norepi vs. isoproterenol for beta adrenoreceptors:
High to low: isoproterenol, epi, norepi
Epinephrine has an affinity for
alpha 1, alpha 2, beta 1, beta 2, and beta 3 receptors
low dose: beta effects
high doses: alpha effects
Epinephrine is used for
anaphylaxis, local anesthetics, and cardiac arrest
Norepinephrine has an affinity for
alpha 1 and beta 1 (little effect on beta 2)
Norepinephrine is used to treat
shock (extravasation can result d/t vasoconstriction) q
Isoproterenol has affinity for
beta 1 and beta 2
Isoproterenol is used to treat
acute asthma (now obsolete) and cardiac stimulant
Dopamine has an affinity for
low dose: D1 in renal, mesenteric, coronary vascular beds
medium doses: beta 1
higher doses: alpha 1
Dopamine is used to treat
shock, HF, increase blood flow to kidneys
Dobutamine has an affinity for
beta 1 primarily
Dopamine is used to treat
acute HF
The predominant effects of adrenergic receptor agonists on alpha 1
vasoconstriction (skin/splanchnic beds)
Smooth muscle- contracts (except GI) & trophic effect (BPH)
GI/GU sphincters- contract
Eye-mydriasis
The predominant effects of adrenergic receptor agonists on alpha 2
decrease NE release (presynaptic)
CNS-inhibit sympathetic outflow
Platelet aggregation
Pancreas: decrease insulin
The predominant effects of adrenergic receptor agonists on beta 1
increased HR, contractility
effects on rhythm
kidney- renin release
Trophic effect- hypertrophy
The predominant effects of adrenergic receptor agonists on beta 2
Bronchodilation vasodilation (esp. skel m beds) most smooth muscle relaxes skeletal muscle contracts- tremor (hypokalemia/increase K+ uptake) GI/GU- relax Uterine smooth muscle relax Glycogenolysis
Indirect acting adrenergic agonists include
tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors- block NE reuptake
Monamine oxidase inhibitors (MAOIs)- prevent breakdown of catecholamines in presynaptic terminal–catecholamines accumulates in vesicles
The effects on alpha 1 receptor agonists include
Increased vascular tone, increased PVR, increased BP and mydriasis
The clinical uses of alpha 1 receptor agonists include
shock
OTC: as decongestants & ophthalmic hyperemia
An example of an alpha 1 receptor agonists includes
phenylephrine
An adverse effect of alpha 1 receptor agonists is
increased BP (seen even w/ nasal spray)
The effects on alpha 2 receptors agonists include
decreased NE release
The clinical uses of alpha 2 receptor agonists include
hypertension (central effects)
The adverse effects of alpha 2 receptor agonists include
sedation because we’re decrease NE which is excitatory in the brain
An example of an alpha 2 receptor agonists is
clonidine
Dexmedetomidine (class & MOA)
selective alpha 2 receptor agonist- CNS actions
suppresses sympathetic NS activity
The effects of dexmedetomidine include
Sedative effects via locus coeruleus and activates endogenous sleep pathways; analgesic effects (spinal cord)
Adverse effects of dexmedetomidine include
decrease HR, decreased SVR, hypotension, transient HTN w/ bolus, bradycardia & decreases RR w/ some decrease in tidal volume
Potential concerns with adrenergic agonists include
CV disease, cerebrovascular disease, diabetes (increased blood sugar), IV extravasation risks, thyroid disease
Nonselective beta blocker includes
propranolol (contraindicated in someone with asthma because it can trigger bronchoconstriction)
Selective beta 1 blocker includes
metoprolol & esmolol
Effects of alpha 1 receptor antagonists include
smooth muscle relaxation, decreased PVR, decreased BP
Clinical uses of alpha 1 receptor antagonists include
hypertension, BPH, pehochromocytoma
Adverse effects of alpha 1 receptor antagonists include
reflex tachycardia, orthostatic hypotension (severe)
An example of an alpha 1 receptor antagonists is
prazosin
An example of a beta 1 (B2) receptor antagonists
propranolol
The effects of nonselective beta receptor antagonists include
decreased HR, decreased force of contraction, decreased renin, and anti-dysrhythmic effects
The clinical uses of beta receptors antagonists include
hypertension, angina pectoris, arrhythmia, myocardial infarction, thyrotoxicosis, heart failure- chronic, stable; other- infantile hemangioma, glaucoma, migraine, prophylaxis, anxiety
The adverse effects of beta antagonists include
bronchoconstriction, creation of arrhythmias, bradycardia, sedation, decreased sexual function, blocking ability to raise sugar w/ typical symptoms of hypoglycemia obscured
Potential concerns with adrenergic antagonists include
respiratory disease, cardiovascular, diabetes (beta blockers may potentiate hypoglycemia & mask signs/symptoms), thyroid disease
A beta 2 receptor agonist would not: A. increase glycogenolysis B. relax uterine smooth muscle C. Relax bronchiolar smooth muscle D. Stimulate renin release
D.
The effects of isoproterenol could be blocked by a/an:
A. alpha 1 adrenergic receptor antagonist
B. muscarinic receptor antagonist
C. Nonselective beta adrenergic receptor antagonist
D. Nicotinic N receptor antagonist
E. alpha 2 adrenergic receptor antagonist
C.
Which would be expected upon administration of a muscarinic agonist drug, but NOT with parasympathetic nerve stimulation?
A. increased bronchial secretion
B. vasodilation
C. contraction of smooth muscle in urinary bladder wall
D. Increased GI Motility
B.
Cholinergic receptors would be found at all of the following sites, EXCEPT: A. adrenal medullary cells B. Juxtaglomerular cells C. Neuromuscular junction D. Sympathetic ganglia E. Sweat glands
B.
