Autonomic Pharmacology 3 Flashcards
What are the 2 classifications for cholinergic agonists?
muscarinic and nicotinic
Name 4 choline esters.
acetylcholine
carbachol
bethanechol
methacholine
Are choline esters poorly or well absorbed from the GI tract?
poorly absorbed
Classify ACh, carbachol, and bethanecol as:
-nicotinic
-muscarinic
-nicotinic and muscarinic
-neither nicotinic nor muscarinic
ACh and carbachol = nicotinic and muscarinic
bethanecol = muscarinic
Which 2 choline esters are not hydrolized by acetylcholinesterase?
carbachol and bethanecol
Which drug (choline ester) is used as a challenge to test for asthma?
methacholine
TRUE or FALSE: muscarinic agonists are both parasympathomimetic and sypathomimetic.
FALSE –> muscarinic agonists are parasympathomimetic
Name 3 muscarinic agonists.
muscarine, oxotremorine, pilocarpine
How do muscarinic agonists affect heart rate?
decreases heart rate
How do muscarinic agonists affect blood vessel dilation/constriction? Explain the process.
muscarinic agonist binds to M3 on the blood vessel ENDOTHELIUM –> nitrogen monoxide (NO) is released from the endothelium –> NO stimulates guanylyl cyclase and production of cyclic GMP –> vascular smooth muscle relaxes –> blood vessel DILATES
How do mAChR agonists affect the bronchiole smooth muscle?
mAChR agonists contract the bronchiole smooth muscle
TRUE or FALSE: increased secretion at the mAChR can relieve asthma.
FALSE –> increased secretion at mAChR EXACERBATES asthma b/c it causes CONTRACTION of bronchiole smooth muscle (restrict airway)
mAChR agonists ____________ secretion of saliva and stomach acid. mAChR agonists also ___________ motility and peristalsis.
Fill in the blanks with either ‘increase’ or ‘decrease’.
mAChR agonists INCREASE both secretion of saliva and stomach acid, and motility and peristalsis
Do mAChR agonists in the bladder promote or inhibit micturition/voiding/urination?
mAChR agonists PROMOTE micturition
What is the major nicotinic agonist?
Nicotine
What are some of the main CNS effects of nicotinic agonists? What do high doses cause? What do the highest doses cause?
- mild STIMULATION
- high dose causes EMESIS
- highest dose causes COMA
TRUE or FALSE: Muscarine can be used as an insecticide.
FALSE –> NICOTINE and MALATHION act as insecticides
Which branch(es) of the ANS does nAChR stimulate? What branch(es) of the ANS does mAChR stimulate?
nAChR - both sympathetic and parasympathetic
mAChR - parasympathetic only
Are nicotine’s cardiovascular effects sympathetic or parasympathetic? Give some examples of the effects.
sympathetic; e.g. hypertension, cardiac stimulation
Are nicotine’s effects on the GI tract sympathetic or parasympathetic? Give some examples of the effects.
parasympathetic; increased secretion and motility
What are the skeletal muscle effects of nAChR?
a) depolarization/excitation
b) hyperpolarization/inhibition
a) depolarization/excitation
What is the function and mechanism of an anticholinesterase?
function: stimulate both nAChR and mAChR
mechanism: prevent hydrolysis of ACh
Do anticholinesterases directly stimulate their receptors? Why or why not?
- NO –> anticholinesterase INDIRECTLY stimulates nAChR and mAChR
- indirect stimulation b/c anticholinesterase acts by preventing hydrolysis of ACh
Which 2 anticholinesterases have reversible action and can be used therapeutically? Describe their structures.
EDROPHONIUM - simple alcohol
NEOSTIGMINE - carbamic ester of alcohols with quaternary/tertiary ammonium group
Which anticholinesterase can be used as an insecticide? Describe its structure.
MALATHION - organophosphate
Which anticholinesterase acts as nerve gas? Describe its structure?
SOMAN - organophosphate
Which 4 locations of the body are anticholinesterases best absorbed?
skin, gut, lung, conjuctiva (eye)
What are the effects of anticholinesterases on the eyes?
miosis, myopia, decreased IOP (intra-ocular pressure)
What are the effects of anticholinesterases on respiration?
bronchiole constriction, increased secretion
What is the effect of anticholinesterases on the gut?
increased motility
What is the effect of anticholinesterases on the bladder?
stimulation (promote micturition)
What are the effects of anticholinesterases on the heart?
bradycardia, decreased cardiac output
TRUE or FALSE: Anticholinesterase effects on the vascular system are dominated by increase in sympathetic tone.
TRUE
TRUE or FALSE: Anticholinesterase effects on the vascular system cause little overall change in blood pressure.
TRUE
What are the effects of anticholinesterases on neuromuscular transmission? What do high doses lead to? What do the highest doses lead to?
general effect: increased strength of contraction
high concentration effect: muscle fasciculations (twitching)
highest concentration effect: depolarizing neuromuscular blockade (paralysis)
What are the effects of anticholinesterases on neuromuscular transmission? What do high doses lead to? What do the highest doses lead to?
general effect: increased strength of contraction
high concentration effect: muscle fasciculations (twitching)
highest concentration effect: depolarizing neuromuscular blockade (paralysis)
What are the effects of nerve gas or insecticide poisoning?
- cardiac arrest
- fluid in lungs
- bronchioconstriction
- blockade of respiratory (skeletal) muscle contraction
Which drug can be used to limit the effects of nerve gas?
ATROPINE
What eye condition can cholinomimetics (cholinergic agonists) be used to treat?
Glaucoma (which involves high intra-ocular pressure (IOP)) can be treated with cholinomimetics (e.g. anticholinesterase) which decrease IOP.
Which 2 drugs below are most likely used to treat urinary retention and postoperative ileus?
a) edrophonium
b) nicotine
c) oxotremorine
d) atropine
a) edrophonium
c) oxotremorine
(This is because muscarinic agonists (and some anticholinesterases) act parasympathetically which relaxes the sphincters. Edrophonium is an anticholinesterase, and oxotremorine is a muscarinic agonist. Atropine, on the other hand, is a cholinergic ANTAGONIST.)
What are the symptoms of myasthenia gravis? What receptor is affected by this disease, and how is it affected? Which class of drugs works best to treat this disease?
symptoms: weakness and fatigability, difficulty opening eyes, resemble neuromuscular block
effect on receptor: DECREASED expression of nAChR at neuromuscular junction
best drug to treat the disease: ANTICHOLINESTERASE (works better than direct acting nicotinic agonists)
What is another name for nicotinic antagonists?
neuromuscular blockers
What is the main therapeutic use of neuromuscular blockers?
paralysis during surgery
What is the main drug used for paralysis during surgery? What was the prototypic drug? Are these drugs muscarinic or nicotinic; agonists or antagonists?
main: SUCCINYLCHOLINE
prototypic: D-TUBOCURARINE
drug type: nicotinic antagonist
What toxin produced by snakes is a nicotinic antagonist? What is the effect?
ALPHA-BUNGAROTOXIN –> paralysis
What is the prototypic drug for muscarinic antagonists? What 2 chemical components does this drug include in its structure?
ATROPINE (base + tropic acid)
Which drug is most likely used to treat tremor symptoms of Parkinson’s disease? Explain your choice.
a) scopolamine
b) oxotremorine
c) atropine
d) succinylcholine
c) atropine
Parkinson’s involves lack of dopaminergic activity and excess of cholinergic activity; antimuscarinic drugs can inhibit the excess cholinergic activity and control the tremor.
Which anticholinergic drug can be used to treat vestibular disturbances (motion sickness)? Classify this drug as muscarinic or nicotinic.
SCOPOLAMINE; muscarinic antagonist
TRUE or FALSE: Atropine can cause sedation.
TRUE (hint: atropine comes from the Atropa belladonna plant, which translates to deadly NIGHTshade)
When the heart is under parasympathetic tone, what is the effect of administering atropine? Explain your thought process.
increased heart rate, force of contraction, and A-V conduction
thought process: mAChR is activated under parasympathetic tone –> parasympathetic tone = decreased heart rate, etc. –> atropine is an mAChR antagonist –> increased heart rate, etc.
What drug is used to treat chronic obstructive pulmonary disease (COPD)? Classify this drug as nicotinic/muscarinic and agonist/antagonist. What are the effects of this drug?
IPRATROPIUM
- muscarinic antagonist
- block parasympathetic tone; bronchodilation; decreased secretion of mucous
What is the overall effect of muscarinic antagonists? (hint: is mAChR under nicotinic or muscarinic tone?)
decrease parasympathetic tone
Which receptors do directly acting sympathomimetics bind to?
alpha and/or beta adrenoreceptors
What are 3 directly acting sympathomimetics?
adrenaline, noradrenaline, isoproterenol (INA)
What are 2 indirectly acting sympathomimetics that displace stored catecholamines from vesicles?
AMPHETAMINE and TYRAMINE
What are 2 indirectly acting sympathomimetics that inhibit catecholamine re-uptake?
COCAINE and TRICYCLIC ANTIDEPRESSANTS
What was John Newport Langley’s main contribution to pharmacology?
idea of drug receptors in ANS
What was Sir Henry Dale’s main contribution to pharmacology?
receptor antagonist, vasomotor reversal
What was Raymond Ahlquist’s main contribution to pharmacology?
alpha and beta adrenoreceptors
Arrange the following sympathomimetics in order of decreasing affinity for alpha adrenoreceptors. Do the same for beta adrenoreceptors.
adrenaline (A), norepinephrine (N), isoproterenol (I)
alpha: A >= N»_space; I
beta: I > A >= N
How many different beta adrenoreceptors are there? What are their affinities for A and NA?
B1: A = NA
B2: A > NA
B3: ???
How many alpha adrenoreceptors are there and what are their subtypes? Which drugs block each receptor?
alpha1 (alpha1a, alpha1b, alpha1c); blocked by PRAZOSIN
alpha2 (alpha2a, alpha2b, alpha2c); blocked by YOHIMBINE
TRUE or FALSE: alpha receptors are more sensitive to agonists than beta receptors.
FALSE: beta more sensitive than alpha
What is the universal antagonist for all alpha receptors?
PHENTOLAMINE
Which drug acts as an agonist for alpha1 receptors?
PHENYLEPHRINE
Which drug acts as an antagonist for alpha1 receptors?
PRAZOSIN
Which drug acts as an agonist for alpah2 receptors?
CLONIDINE
Which drug acts as an antagonist for alpah2 receptors?
YOHIMBINE
Is there a universal agonist and/or antagonist for all alpha receptors? If there is, what is the name of the drug?
ONLY has a universal ANTAGONIST –> PHENTOLAMINE
Is there a universal agonist and/or antagonist for all beta receptors? If there is, what is the name of the drug?
universal agonist: INA
universal antagonist: PROPRANOLOL
Which drug acts as an agonist for beta1 receptors?
DOBUTAMINE
What is the main drug that acts as an antagonist for beta1 receptors?
METROPROLOL (and atenolol, esmolol, acebutolol)
Which drug acts as an agonist for beta2 receptors?
SALBUTAMOL
Which drug acts as an antagonist for beta2 receptors?
no important examples apparently
Which G protein(s) is/are mainly linked with alpha adrenoreceptors?
Gq
Which G protein(s) is/are linked with beta adrenoreceptors?
Gs
Which G protein(s) is/are linked with alpha2 adrenoreceptors?
Gi
