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Muscarinic agonist aka parasympathomimetic Systemic effects?
- SLUDGE (salivation, lacrimation, urinary incont, diarrhea, GI cramps, emesis)
- pupil constrict
- broncho constrict
- decrease hr and conduct
- vasodilation
- GI/GU- increased motility and secretion, bladder contract, sphincter relax- pee
- Increased sweat and saliva
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Muscarinic agonist aka parasympathomimetics
- – muscarine is a true prototype, but bethanechol is a good example of one used clinically (used for urinary retention and delayed gastric emptying)
- "bethanechol when you pee too much and dont poop at all- use bethanechol!"
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Muscarinic agonist contra
- asthma- bronchoconstrict
- Acid-peptic dx- increase gastric secretion
- Coronary insuff- worsen bradycardia
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Pilocarpine
- another muscarinic agonist
- for dry mouth- promotes salivation
- "pilocarpine - to start PAVLOVing"
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m1, m2, m3 ,m4, m5 excite or inhibit?
- odds- excite
- even- inhibit
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Muscarinic antagonist aka sympathomimetics
example?
Systemic effects?
- – "atropine- makes your heart sing"- blocks vagal slowing on SA node- increased HR
- Scopalamine-
- Pupil Dilation
- GI GU- plug up
- Lung- decrease secretions- dry up
- Tachy- dose dependent
- Glands- block sweating and salivation
- CNS (Scopalamine)- reduce parkinsonian tremor and altered vestibular function
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atropine intox? aka antimuscarinic poisoning
aka- anticholinergic syndrome
Clinical manifestations?
Treatment?
- mad as a hatter
- blind as a bat
- dry as a bone (mouth)
- red as a beet (flushing)
- hot as a furnace
- use a muscarinic AGONIST- overcome muscarinic receptor blockade- Physostigmine "(antillirium)- fights atropine dilirium"
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tiotropium (spiriva)
ipratropium
for?
which is better?
- -COPD acts at m1,2,3- bronchodilation, BETTER
- - COPD- nonselective for m1,2,3- potential for paradoxical bronchoconstriction
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Nicotinic agonist (remember cholinergic agonists are either nicotinic or muscarinic!)
2 types of Nicotinic?
- Direct– nicotine, succinycholine
- Indirect- AChEsterase inhibitor
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ACh metabolism by AChE
Process?
Sites of action?
- HYDROLYSIS!
- -Anionic Site- binds ACh to enzyme
- -Esteratic Site- hydrolysis breaks ester bond
-
Anticholinesterases-
3 major groups?
Duration of action?
Alcohols<carbamates<organophosphates
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Organophosphate
Example
- AntiCholinesterase inhibitor (irreversable- need new AChE)
- Ex: echothiophate
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Carbamate?
Example?
- Anticholinesterase inhibitor (reversable)
- ex: Physostigmine- (reverse anticholinergic syndrome from atropine)
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Simple Alcohol?
example
- Competitive AntiCholinesterase Inhibitor- competes for ANIONIC site
- Edrophonium
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Organophosphate poisoning treatment
Symptoms of exposure
- -Oxygen
- -Atropine + Pralidoxime
- -Benzos
Same as Parasympathetic SLUDGE + bradycardia+ muscle fasciculations+CNS slurring
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Myasthenia Gravis
what happens?
Diagnosis?
Treatment?
Antibody made blocks ACh binding to receptor
Dx- Edrophonium test, + test shows obvious muscle strength improvement for 5 min
- Immunosupress Prednisone
- Pyridostigmine
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Ganglionic blocker example –
mecamylamine- noncompetitive blocker- autonomic NS paralysis
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DEPOLARIZING NMJ blocker
– succinylcholine
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NON-depolarizing blocker
– again, like muscarine, d-tubocurarine (or curare) is a prototype not used often clinically; but if you remember that these drugs end in “onium” and “urium” you should be ok
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Acetylcholinesterase inhibitor
– simple alcohol – Edrophonium (note – this one ends in “onium” but is NOT an NMJ blocker!)
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Acetylcholinesterase inhibitor
– carbamate – Neostigmine
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Acetylcholinesterase inhibitor
– organophosphate – Echothiophate
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Alzheimers and Cholinergics
-What do muscarinic blocking agents do?
- ChAT levels and ACh?
-# of nicotinic and Muscarinic receptors
- induce memory loss
-dramatic ChAT drop- reduced ACh output
- reduced in alzheimers
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blood vessels- sympathetic or par tone?
cholinergic or adrenergic?
- - sympathetic
- - adrenergic
-
dominant tone at rest?
parasympathetic
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sweat glands- sympathetic or para tone?cholinergic or adrenergic?
- sympathetic tone
- cholinergic
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Dominant tone?- para or sympat with addition of a muscarinic receptor agonist
para- more motility observed
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Dominant tone?- para or sympat with addition of a muscarinic receptor anatagonist
- sympathetic- para is blocked
- less motility
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Dominant tone?- para or sympat with addition of a nicotinic receptor antagonist
neither, both sympathetic and parasympathetic tone are blocked
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Dominant tone?- para or sympat with addition of a beta adrenergic receptor agonist
- sympathetic tone is increased
- motility is decreased
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Dominant tone?- para or sympat with addition of a beta adrenergic antagonist
- parasympathetic-
- sym is blocked- greater motility and tone
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How can a nictinic receptor agonist act as a blocker?
initial stimulation- after ion flow has occurred- unbinding of agonist has not occurred and therefore acts as a blocker
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nicotinic and muscarinic- ion or g protein?
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nicotine effects
- muscle- depolarization fasciculation
- adrenal medulla- epi release- increase hr/bp
- cns- exicte, convulsion, resp stim, coma
- ganglia- depends on dom tone, secretion stim and n/v/d
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nicotinic receptor anatagonist aka ganglionic blockade effect on BV?
hypotn
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nicotinic receptor anatagonist aka ganglionic blockade effect on sweat glands
anhidrosis
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nicotinic receptor anatagonist aka ganglionic blockade effect on heart
tachy
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nicotinic receptor anatagonist aka ganglionic blockade effect on pupillary fxn and lens
mydriasis and blurred vision(cyclopegia)
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nicotinic receptor anatagonist aka ganglionic blockade effect on gut
decreased tone and motility
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nicotinic receptor anatagonist aka ganglionic blockade effect on bladder
urinary retentio
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nicotinic receptor anatagonist aka ganglionic blockade effect on salivary gland
xerostomia
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ganglionic therapeutic use
- control hemorrhage in surgery
- severe htn
- dissecting aortic aneurysm
- autonomic reflexia- sc injury
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succinycholine
- depolarizing blocker- binds to nicotinic receptors at motor end terminal
- na and ca diffuse into cell and depolarizes this is phase I blockade
- SUx is not metabolized by AChE-remains attached and channel stays open
- new action potential cannot occur until repolarization- have paralyzation because contractions cannot occur- Phase II
- sux is metabolized by palsma cholinesterase
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SUX contra
causes hyperkalemia- worry in pts prone to this like burn victims
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