Cholinergic Agonists/Antagonists Flashcards
ACh stimulates what two types of receptors?
muscarinic
nicotinic
Muscarinic (M) Receptors found in what organs? (6)
(parasymp) eye GI Bladder salivary glands sweat glands heart
Muscarinic Receptors respond to what?
muscarine
M1, M3 2ndary messengers?
Gq -> DAG -> ↑ Ca2+ (excitatory)
M2 2ndary messenger?
Gi -> ↓ AC (inhibitory)
Nicotinic Receptors found where?
brain
adrenal medulla
autonomic ganglia
neuromuscular jxn
Nicotinic Receptors respond to?
nicotine
N receptor 2ndary messenger?
Na+ Ion channels (excitatory)
Example of Direct-Acting agonists?
muscarinic agonists stim muscarinic receptors
Example of Inderect-Acting agonists?
Cholinesterase inhibitors ↓ ACh breakdown
Ѧ stims M and nicotinic receptors longer
Direct Agonists? (6)
ACh Methacholine Carbachol Bethanechol Pilocarpine Nicotine
Which direct agonists are cholinergic agonists?
ACh
Bethanechol
Properties of ACh vs Bethanechol?
ACh:
stim M and nicotinic receptors
hydrolyzed by AChE
Bethanechol:
stim M recpetors
resists AChE
doesn’t enter brain
Which direct agonists are muscarinic agonists?
Muscarine
Pilocarpine
What 2 kinds of receptors are extra sensitive to pilocarpine?
sweat
salivary
Bethanechol has the most affect on what? (2)
bladder
GI
Side Effects of Muscarinic Agonists? (8)
salivation/tears N/V diarrhea HA visual disturbances bronchospasm bradycardia shock
Tx for mushroom poisoning (muscarine)?
atrophine (antagonist)
albuterol
Contraindications for muscarine (3)
1) asthma/COPD (bronchoconstriction)
2) peptic ulcer (↑ acid prdxn)
3) bowel obstruction (↑ peristalsis)
Nicotinic (N) receptors are located on what kind of proteins?
ligand-gated Na+ channels
Nicotinic receptors are found where? (3)
1) autonomic ganglia (Nn)
2) skeletal mm (Nm)
3) brain (Nn)
N recpetors are rapidly what?
desensitized to nicotine
Stim of N receptors in brain results in:
low doses
high doses
toxic doses
low doses = ↑ alertness/attention
high doses = tremor, emesis, ↑ respiration
toxic = convulsions
Stim of N receptors in ganglion activates symp or parasymp?
activate BOTH
Stim of N receptors in ganglion results in:
symp effects
parasymp effects
symp = HTN, tachycardia, vagal bradycardia
parasymp = N/V, diarrhea, urination
Nicotine toxicity results in? (4)
vomiting
CNS stim = convulsions, coma, resp arrest
skeletal mm depol = paralysis
HTN, arrhythmia
Tx for nicotine toxicity?
atropine = ↓ parasymp by blocking M receptors
anticonvulsants
respiratory assistance
Varenicline (Chantix) is what?
Used for what?
S/E?
part agonist of N rec in brain
↓ nicotine craving
N/V, gas, constipation
sleep and psych disturb
Cholinesterase Inhibitors do what?
↑ time ACh available to stim receptors
4 types of Cholinesterase Inhibitors?
1) neostigmine (Prostigmin)
2) physostigmine (Eserine)
3) edrophonium (Tensilon)
4) organophosphates
Neostigmine inhibits AChE how?
binds -> slows AchE
Carbamates inhibit AChE how?
covalent bond -> slows AchE
Edrophonium inhibition of AChE?
reversible
short acting (5 min)
injected
no CNS penetration
Organophosphate inhibition of AChE?
become irreversible w/ aging
long lasting
Pralidoxime (2-PAM) is?
strong nucleophile,
effective at NMJ,
no CNS,
prevents aging of enz so use to counteract organophosphates
AChE Inhibitors effects on:
CNS
Eye
GI, Bladder
Respiratory
CNS = ↑ alertness, memory
toxic: convulsions, resp arrest
Eye = miosis, near vision
GI, Bladder = stim, diarr, urination
Respiratory = salivation, secretions, bronchoconstriction
AChE Inhibitors effects on cardiovascular?
All ganglia activated: parasym dominates
bradycardia, ↓ contraction force, ↓ CO
little effect on BP (no cholinergic innerv)
AChE Inhibitors effects on NMJ:
low dose
high dose
low = ↑ ACh action, ↑ mm strength
high = twitched, fasiculations, paralysis
Neostigmine (Prostigmin) effects on AChE?
last 4 hrs no brain absorp ↑ bladder motility reverse NM blockade post surgery tx myasthenia gravis
Edrophonium (Tensilon) used for what?
1) diagnose myasthenia gravis (immediate improvement of sxs = + result)
2) monitor AChE inhibitor tx (will ↓ strength if dose too high)
Echothinophate is?
Used for?
organophosphate AChE inhibitor
very long acting
eyedrops to ↓ intraocular pressure of narrow-angle glaucoma
Glaucome tx
direct agonists
cholinesterase inhibitors
direct/AChE inhibitor combos
Myasthenia Gravis
autoimmune dx,
antibodies ↓ # of N receptors,
causes mm weakness w/ use,
small mm of head most effected (e.g. eye)
AChE inhibitor toxicity results?
SLUDGE: Salivation Lacrimation Urination Defecation Gastric distress Emesis
NM stim followed by paralysis
Tx for organophosphate AChE inhibitor poisoning? (4)
atropine
2-PAM w/i 4 hrs
diazepam
respiration support
Atropine effects?
0.5 mg
1 mg
2 mg
5 mg
10 mg
0.5 mg = dry mouth, ↓ sweat
1 mg = ↑ HR, thirsty
2 mg = blurred vision, tachycard, palp
5 mg = ф urine, hot/dry
10 mg = rapid/weak pulse, ataxia, coma
Muscarinic Antagonist (antichol) drugs method of action?
Prototype drug?
bind M receptor, displacing ACh
Atropine
Scopolamine method of action?
Administration?
Effects on CNS?
Used for?
binds M receptors, displaces ACh
patch
euphoria, amnesia, drowsiness
hallucination, coma
motion sickness
Opthamology M antag drug for dilation?
Tropicamide (6 hrs)
M antagonist drug effects on cardiovas?
↓ tone = tachycardia
M2 receptors blocked = ↑ NE
little effect on babies/elderly cuz vagal tone is low
M antagonists drug effects on eye?
↓ tone pupil dilates lens flattens (can;t focus) phtotphobia dry eyes
M antagonist drug effects on respiration?
reverse bronchoconstriction
best for COPD or acute asthma attack
M antagonist drug effects on GI?
↓ motility and secretions
↓ tone
antispasmodic
M antagonist drug effects on bladder?
↓ motility
M antagonist drug effects on secretions?
↓ sweat, saliva and tears
dry eyes, mouth
Use of M Antagonists for Opthamology?
Prototype?
eye dilation for exam
cycloplegia (IOM paralysis)
tropicamide
Use of M Antagonists for cardiac?
↓ bradycardia
reverse heart block
Atropine used post MI
Ipatropium (Atrovent) is what drug type?
Used for?
M antagonist
COPD, acute asthma
Tolterodine (Detrol) is what drug type?
Used for?
M antagonist (M3)
overactive bladder
Oxybutynin (Ditropan) is what drug type?
Used for?
M antagonist
bladder spasm post surgery
Contraindications for M Antagonists?
narrow angle glaucoma (↑ IO pressure)
benign prostate hyperplasia (↑ urine difficulties)
Atropine overdose signs?
dry as bone
blind as bat
red as beet
mad as hatter
Neuromuscular Blockers do what?
block nicotinic receptors on skeletal mm
Non-depolarizing NM blockers mode of action?
Administered?
Reverse effect w/ what?
Used for?
reversible competitor for ACh receptors
IV
AChE Inhibitors (↑ ACh)
mm relax in surgery
Depolarizing NM blocker action?
temp paralysis of extremities, face/neck, respiration
Can results in hyperkalemia = MI
Depolarizing NM blocker prototype drug?
succinylcholine
Contraindications for succinylcholine?
< 8yo soft tissue damage/burns nontraumatic rhadbomylosis quad or paraplegia MD
NM blockers enhanced by what drugs?
anesthetics
aminoglycoside antibiotics
TCN
Ca2+ channel blockers
Ganglion Receptor Blocker mode of action?
block nicotine receptors in all auto ganglia,
non-depol competitive antagonist,
↓ total output of ANS
