Cholinergic Flashcards
Acetylcholine: class
the original cholinergic agonist, naturally-occuring
Cholinergics: aka what?
parasympathomimetics. bind directly to cholinoceptors.
Acetylcholine: indication
glaucoma
Acetylcholine: why not widely used as therapy?
many actions, leads to diffuse effects, rapid inactivation by cholinestases
Carbachol: class
Cholinergic agonist
Carbachol: indication
Glaucoma
Carbachol: action
locally instilled in the eye, it mimics the effects of ACh, causing miosis and accomodation (ciliary muscle in a state of contraction).
Bethanechol: class
Muscurinic agonist
Bethanechol: indication
Neurogenic illeus
Bethanechol: PD
binds to muscarinic cholinergic receptors and causes contraction of smooth muscle
Bethanechol: tox
reflex tachycardia (due to vasodilation), bronchoconstriction, increased secretory activity (sweat, GI/respiratory secretions)
Bethanechol: special
has been replaced by newer drugs that act upstream on the neurons that release ACh (increase the release of ACh)
Methacholine: class
Muscurinic agonist
Methacholine: indication
Asthma dx: aerosolized form used to challenge pts during diagnostic testing for asthma
Methacholine: PD
binds to muscarinic cholintergic receptors in airway and causes bronchoconstriction; asthmatics with hyperreactive airways respond to lower concentrations
Methacholine: tox
bronchoconstriction, increased secretory activity (sweat, GI/respiratory secretions)
Pilocarpine: class
Muscurinic agonist
Pilocarpine: indication
glaucoma
Pilocarpine: PD
activates muscarinic receptors on the pupillary sphincter muscle, causing the muscle to stay relatively constricted (this prevents the muscles of the iris from blocking the already narrow angle between the sclera and the iris, and thus allows the aqueous humor to drain better)
Pilocarpine: tox
increased secretory activity (lacrimation)
Pilocarpine: route
topical
Nicotine: class
Nicotinic agonist
Nicotine: indication
smoking cessation
Nicotine: PD
binds to nicotinic receptors; slower action than the nicotine found in cigarettes
Nicotine: tox
CNS stimulation (drug is lipid soluble), neuromuscular junction depolarization leading to spasms and then paralysis (if given high dose); can cause increased sympathetic activity (since nicotinic receptors are in ganglia), leading to toxicity related to increased secretions from the adrenal glands
Varenicline: class
very selective partial agonist of a2-b4 nicotinic receptors (so nicotine can’t access)
Varenicline: indication
smoking cess
Varenicline: PD
CNS mesolimbic dopamine, partial a4-b2 stimulation prevents low dopamine and cravings; also prevents nicotine from creating dopamine surges, No chemical reward
Varenicline: PK
well absorbed; peak 4 h, t1/2 = 24 h; excreted primarily in urine as unchanged drug
Varenicline: special
Reports of suicidal thoughts and aggressive and erratic behavior → patients and caregivers should be instructed about the importance of monitoring for neuropsychiatric symptoms, and to communicate immediately with the prescriber the emergence of agitation, depression, unusual changes in behavior, or suicidality. Psychiatric patients – use extreme caution. Contraindicated in pregnancy/lactation. Causes drowsiness, caution operating machinery
Varenicline: monitor
neuropsychiatric symptoms
Edrophonium: class
Short acting AChE inhibitor
Edrophonium: indication
Myesthenia Gravis Dx
Edrophonium: PD
blocks action of cholinesterases, thereby increasing the action of ACh; an alcohol; does NOT form a covalent bond with esteratic site on ChE’s
Edrophonium: PK
very short acting
Edrophonium: special
charged so does not cross BBB
Neostigmine: class
Intermediate acting AChE inhibitor
Neostigmine: indication
Myesthenia Gravis Rx
Neostigmine: PD
blocks cholinesterases, thereby increasing the effect of ACh (restores neuromuscular transmission in MG patients); bind covalently to esteratic site of cholinesterase and leave behind a carbamoyl residue (blocks enzyme) that is released slowly over hours
Neostigmine: PK
longer acting than edrophonium but not as long as organophosphate ChE inhibitors
Neostigmine: tox
overdose results in increased muscarinic effects (cholinergic crisis)
Neostigmine: special
does not cross BBB
Physostigmine: class
Intermediate acting AChE inhibitor
Physostigmine: indication
Rx CNS side effects of muscarinic agonists
Physostigmine: PD
blocks cholinesterases, thereby increasing the effect of ACh (restores neuromuscular transmission in MG patients); bind covalently to esteratic site of cholinesterase and leave behind a carbamoyl residue (blocks enzyme) that is released slowly over hours
Physostigmine: PK
longer acting than edrophonium but not as long as organophosphate ChE inhibitors
Physostigmine: tox
overdose results in increased muscarinic effects (cholinergic crisis); enters the brain, and ChE inhibitors in CNS can have dangerous effects
Physostigmine: special
crosses the BBB (uncharged and lipid soluble)
Organophosphates: what fits in this category?
Sarin, soman, parathion, malathion
Organiphosphates: class
Long acting AChE inhibitor
Organiphosphates: indication
insecticides, nerve gasses, WMD. not really used medically
Organiphosphates: PD
blocks cholinesterases, thereby increasing the effect of ACh (restores neuromuscular transmission in MG patients); bind covalently to esteratic site of cholinesterase and leave behind a phosphate residue (blocks enzyme) that is released slowly over days to weeks
Organophosphates: PK
MUCH longer acting than the other two types of ChE inhibitors (carbamates and edrophonium)
Ectothiophate: class
Long acting AChE inhibitor
Ectothiophate: indication
glaucoma
Ectothiophate: PD
blocks cholinesterases, thereby increasing the effect of ACh (restores neuromuscular transmission in MG patients); bind covalently to esteratic site of cholinesterase and leave behind a phosphate residue (blocks enzyme) that is released slowly over days to weeks
Ectothiophate: PK
MUCH longer acting than the other two types of ChE inhibitors (carbamates and edrophonium)
Pralidoxime: class
cholinesterase regenerator (rescue drug - action opposes that of organophsphate ChE inhibitors)
Pralidoxime: indication
accidental exposure to insecticides or nerve gases that contain organophosphate ChE inhibitors
Pralidoxime: PD
has high affinity for phosphate group that is bound to esteratic site of ChE (from organophosphate); binds phosphate group, which frees cholinesterase
Pralidoxime: special
Give soon after exposure
Metoclopramide: class
Indirect cholinergic, stimulates ACh release
Metoclopramide: indication
Neurogenic illeus, nausea
Atropine: class
non-selective muscarinic blocker
Atropine: indication
to dilate pupils, bradycardia (raises HR), to decrease secretions, organophosphate poisoning (insecticide, etc – blocks action of ACh; given with Pralidoxime)
Atropine: PD
lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system (dilates eye, increases HR, reduces airway secretions, etc)
Atropine: PK
effect lasts 4-8 hours (except in eye, where they can last up to 72 hrs)
Atropine: tox
Atropine poisoning (intensification of sympathetic effects in same end organs):
Mad as a hatter: delirium, hallucinations
Blind as a bat: mydriasis, photophobia, blurred vision (cycloplegia)
Dry as a bone: block of secretions (salivary, sweat)
Red as a beet: prostaglandins?, fever, anhidrosis (inability to sweat), dilation of vessels
Hot as a hare: hyperthermia resulting from anhidrosis; can be lethal in infants
Other side effects of atropine include:
urinary retention (block of detrusor muscle)
bronchodilation
constipation
tachycardia
Atropine: excr
by both liver and kidney
Atropine: special
lipid soluble (can cross BBB); use with caution in infants because of risk of hyperthermia; don’t use in men with prostatic hyperplasia
Scopolamine: class
Muscurinic blocker
Scopolamine: indication
Motion sickness, pupil dilation
Scopolamine: PD
lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system (dilates eye, increases HR, reduces airway secretions, etc)
Scopolamine: special
crosses BBB (effect on motion sickness via CNS)
Benztropine: class
Muscurinic blocker
Benztropine: indications
reduce symptoms of Parkinson’s and parkinsonism (decreases tremors)
Benztropine: PD
lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system (dilates eye, increases HR, reduces airway secretions, etc)
Succinylcholine: class
Depolarizing nicotinic blocker
Succinylcholine: indication
Surgical paralysis
Succinylcholine: PD
persistently depolarizes neuromuscular end plate, which causes flaccid skeletal muscle paralysis to develop desensitization; functions like ACh at NMJ; does NOT get to ganglia
Succinylcholine: PK
short acting (effects of bolus last 5-7 min)
Succinylcholine: excretion
cleared by plasma ChE
Succinylcholine: interaction
Anesthetic gases and aminoglycoside antibiotics synergize with succinylcholine
Succinylcholine: special
only NMJ depolarizing blocker in clinical use; do NOT give to patients lacking ChE (causes prolonged paralysis)
Tubocurarine: class
Non-depolarizing nicotinic blocker
Tubocurarine: indication
Surgical paralysis
Tubocurarine: PD
directly blocks receptors on nicotinic end plate, thereby causing flaccid skeletal muscle paralysis
Tubocurarine: PK
lasts 30-60 min (longer than succinylcholine)
Tubocurarine: special
Throughout paralysis, consciousness and sensorium is intact never give these types of drugs to an unanesthetized patient, and never let a patient emerge from anesthesia before reversing the paralysis with neostigmine
Rocuronium: class
Non-depolarizing nicotinic blocker
Rocuronium: indication
Surgical paralysis
Rocuronium: PD
directly blocks receptors on nicotinic end plate, thereby causing flaccid skeletal muscle paralysis
Rocuronium: PK
shorter acting than d-tubocurarine
Rocuronium: excr
liver
Rocuronium: special
don’t give to pts with liver disfunction
Botulinum toxin: class
bacterial exotoxin
Botulinum toxin: indication
facial wrinkles!
Botulinium toxin: PD
blocks neuronal release of ACh; causes botulism; Interferes with docking proteins on the interior of the nerve membrane (vesicles containing ACh cannot dock properly and therefore cannot release ACh) leads to flaccid paralysis; symptoms similar to atropine poisoning except for the CNS effects
Cisatracurium: class
Non-depolarizing nicotinic blocker
Cisatracurium: indication
Surgical paralysis
Cisatracurium: PD
directly blocks receptors on nicotinic end plate, thereby causing flaccid skeletal muscle paralysis
Cisatracurium: PK
shorter acting than d-tubocurarine
Cisatracurium: excr
cleared by liver and plasma esterases
Trimethaphan: class
NN (ganglionic) blocker
Trimethaphan: indication
HTN: only to treat HTN crisis, or for controlled hypotension during surgery
Trimethaphan: PD
blocks nicotinic transmission with both sympathetic and parasympathetic ganglia (NN receptors); produces veno- and vaso-dilatation
Trimethaphan: PK
useful only when given iv; produces fall in BP within minutes; partly metabolized, and partly excreted by kidneys
Trimethaphan: tox
watch out for sudden, severe drop in BP; also fall in HR; also, reduction in just about any sympathetic or parasympathetic response
Trimethaphan: interactions
additive effects with most other antihypertensives;
Trimethaphan: special
patients are quite miserable, hence only used during general anesthesia; also, helps to tilt patient to help control BP
Trimethaphan: monitor
minute to minute monitoring of BP (and HR)
Oxybutynin: class
Muscurinic blocker
Oxybutynin: indication
Urgency and bladder spasms
Glycopyrrolate: class
Muscurinic blocker
Glycopyrrolate: indication
Urgency and bladder spasms
