Auto drugs II and III Flashcards
Bethanecol: class, mech, therapeutics, important SE’s, Other SE’s, Misc
Class: Direct acting carbamic acid ester
Mech: Direct-acting muscarinic cholinomimetic
Thera: Post-operative and neurogenic ileus; urinary retention (bowel and bladder smooth muscle ACh-innervated)
Important SE’s: SLUDGE
Muscarine:
Class: Direct acting non-ester alkaloid
Mech: Direct-acting muscarinic cholinomimetic
Thera: —
Important SE’s: SLUDGE
Pilocarpine (Salagen): how different from muscarine?
Thera: Glaucoma (ACh activates sphincter and ciliary muscles of eye)
Cevimeline (Evoxac): how different from muscarine?
Thera: Dry mouth (in, e.g., Sjogren’s, post-radiation therapy; via increased salivation)
Neostigmine (Prostigmin)
Class: Indirect acting carbamate
Mech: AChE inhibitor (short acting)
Thera: Post-operative and neurogenic ileus; urinary retention; myasthenia gravis; reversal of neuromuscular blockade
Important SE’s: SLUDGE + general increase in cholinergic neurotransmission; paralysis
Misc: Lasts 0.5-2 hours
Physostigmine (Eserine)
Class: Indirect acting carbamate
Mech: AChE inhibitor (short acting)
Thera: Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Important SE’s: SLUDGE + general increase in cholinergic neurotransmission; paralysis
Misc: Lasts 0.5-2 hours
Donepezil (Aricept)
Class: Indirect acting non-ester
Mech: AChE inhibitor
Thera: Alzheimer’s (amplifies endogenous ACh in brain)
Important SE’s: see neostigmine
Edrophonium (Enlon)
Class: Indirect acting non-ester Mech: AChE inhibitor (v. short acting) Thera: Myasthenia gravis (differentiating deficiency versus ACh crisis); ileus Important SE's: see neostigmine Misc: Lasts 5-15 minutes
Echothiophate (Phospholine)
Class: Indirect acting organophosphate
Mech: AChE inhibitor (long acting)
Thera: Glaucoma (ACh activates papillary sphincter and ciliary muscles of eye)
Important SE’s: SLUDGE + general increase in cholinergic neurotransmission; paralysis
Misc: Lasts >100 hours
Pralidoxime (Protopam)
Class: Strong nucleophile
Mech: Regenerates phosphorylated AChE
Thera: Poisoning by nerve gas, insecticide
Sarin
Class: Very potent indirect acting organophosphate
Mech: AChE inhibitor
Thera: Volatile nerve gas
Important SE’s: see neostigmine
Other SE’s: Death
Misc: Treat with pralidoxime and atropine before aging
Atropine
Class: Tertiary amine antimuscarinic
Mech: Blocks muscarinic receptors
Thera: Mydriasis; cycloplegia
Important SE’s: General block of muscarinic functions
Scopolamine (Transderm-Scop): how different from atropine?
Thera: Prevent or reduce motion sickness
Misc: well-absorbed with central effects, given by injection, mouth, or transdermal patch
Dicyclomine (Bentyl): how different from atropine?
Thera: Reduce transient hypermotility
Tropicamide (Mydriacyl): how different from atropine?
Thera: Mydriasis; cycloplegia
Misc: Very rapidly metabolized
Tolterodine (Detrol): how different from atropine?
Thera: Treat transient cystitis; postoperative bladder spasms; incontinence
Benztropine (Cogentin): how different from atropine?
Thera: Treat manifestations of Parkinson’s disease
Misc: Crosses BBB
Ipratropium (Atrovent)
Class: Quarternary amine antimuscarinic
Mech: Blocks muscarinic receptors
Thera: Bronchodilation in asthma or COPD
Important SE’s: General block of muscarinic functions
Misc: can be aerosolized to maximize bronchial effects and minimize central effects
Tiotropium (Spiriva): how different from ipratropium?
Misc: Longer acting than ipratropium
Hexamethonium (Methium)
Class: Ganglionic blocker (quarternary amine)
Mech: Blocks ganglionic (Nn) receptor at both symp and parasymp ganglia, and sympathetic tone
Thera: Hypertensive crisis; “Bloodless” field surgery
Misc: Rarely used
Mecamylamine: how different from hexamethonium?
Can cross the BBB!!!!
Succinylcholine (Anectine)
Class: Depolarizing blocker
Mech: Overstimulation of nicotinic receptor (NM), leading to desensitization of muscle unit to further ACh stimulation
Thera: Brief procedures (e.g., tracheal intubation, reset dislocated joints)
Important SE’s: Respiratory paralysis; disturbance of autonomic function (could affect NN type nicotinic receptors a bit)
Misc: Produces flaccid paralysis within 1 minute
Tubocurarine (Curare)
Class: Nondepolarizing blocker
Mech: Blocks nicotinic (Nm) receptor
Thera: Muscle relaxant for surgery w/o deep anesthesia
Important SE’s: Respiratory paralysis; disturbance of autonomic function
Misc: Lasts 30-60 minutes
Mivacurium (Mivacron)
Class: Nondepolarizing blocker
Mech: Blocks nicotinic (Nm) receptor
Thera: Muscle relaxant for surgery w/o deep anesthesia
Important SE’s: Respiratory paralysis; disturbance of autonomic function
Misc: Rapidly hydrolyzed, short acting
Botulinum toxin A (Botox)
Class: Local paralytic
Mech: Blocks vesicle fusion and ACh release on presynaptic terminal by degrading SNAP-25
Thera: Reduce frown lines and wrinkles; achalasia; strabismus; oromandibular dystonia
Typical location of the M1 receptor?
CNS neurons, symp postgang neurons, some presynaptic sites
M2 receptor locations?
Myocardium, smooth muscle, some presynaptic sites; CNS neurons
M3 receptor locations?
Exocrine glands, vessels (smooth muscle and endothelium ); CNS neurons
M4 receptor locations?
CNS neurons; possibly vagal nerve endings
M5 receptor locations?
Vascular endothelium, especially cerebral vessels; CNS neurons
Nicotinic NN locations? Result of ligand binding?
Postganglionic neurons, some presynaptic cholinergic terminals;
opening of Na, K channels, depol
Nicotinic NM locations? Result of ligand binding?
Skeletal muscle neuromuscular end plates;
opening of Na, K channels, depol
Knock out M3 receptor what happens with the pupil?
Continue to dilate pupil
In the context of bronchoconstriction, what do you see with M3 (-/-) vs M2 (-/-)?
You see a decrease in bronchoconstriction because you’re downregulating receptors that contract smooth muscle;
you would see increased bronchoconstriction since normally Ach can be released to act on M2 autoreceptors to e.g. prevent release of Ach and allow for bronchodilation, but with no M2 receptors you have unopposed bronchoconstriction!!
T/F: there is a lot of selectivity of drugs within the nicotinic and muscarinic receptor families
False: there is very little selectivity within these families
The direct-acting agents ____ bind to and activate ___ or ___ receptors; what do indirect-acting agents act on?
directly; muscarinic or nicotinic;
inhibit Ach-ase
In the eye, what do direct-acting cholinergic agents act on?
Sphincter muscle of iris: contraction (miosis);
Ciliary muscle: contraction for near vision
In heart, what do direct-acting cholinergic agents act on?
- SA node (decrease in rate: negative chronotropy)
- Atria (decrease in contractile strength: negative inotropy; also a decrease in refractory period)
- AV node (decrease in conduction velocity: negative dromotropy; also an increase in refractory period)
- Ventricles: small decrease in contractile strength
In blood vessels, what do direct-acting cholinergic agents act on?
- Arteries: dilation (via EDRF, or nitric oxide); constriction (high-dose direct effect)
- Veins: dilation (via EDRF, or nitric oxide); constriction (high-dose direct effect)
In lung, what do direct-acting cholinergic agents act on?
Bronchial muscle: contraction (bronchoconstriction)
Bronchial glands: stimulation
In GI tract and bladder, what do direct-acting cholinergic agents act on?
- Motility: increase
- Sphincters: relaxation
- Secretion: stimulation;
- Detrusor: contraction
- Trigone and sphincter: relaxation
Glands: sweat, salivary, lacrimal, nasopharyngeal, what will direct-acting cholinergic agents act on?
Secretion
Neostigmine causes ____ effects on muscle strength due to _____ in Ach levels (at ___ doses) and then what at ___ doses?
How can one determine where exactly someone is on the neostigmine curve?
biphasic; increases; low;
depolarizing block; higher;
Use edrophonium to help identifity myasthenia gravis; and also if muscle strength will increase or decrease
Mnemonic for overdose of atropine (and other muscarinic antagonists)?
- Dry as a bone (reduced sweating, lacrimation, salivation)
- Blind as a bat (blockate of accommodation and excessive pupillary dilation)
- Red as a beet (dilation of cutaneous vessels in upper body perhaps because of temp increase associated with sweat gland inhibition and antagonism of alpha1 receptors
- Mad as a hatter (inhibition of CNS muscarinic receptors with a series of complex consequences)
In the case of cholinesterase inhibitor toxicity, what should therapy be?
For these indirect-acting agents, give atropine and pralidoxime (latter to give you back ACase activity)
Cholinesterase inhibitors are very effective at ____ the effects of ________ blockers; in contrast, what happens with depol block relative to cholinesterase inhibitors?
blocking; non-depolarization;
it’s unaffected, or even increased!!
Cevimeline (Evoxac)
Class: Direct acting non-ester alkaloid
Mech: Direct-acting muscarinic cholinomimetic
Thera: Dry mouth (in, e.g., Sjogren’s, post-radiation therapy; via increased salivation)
Important SE’s: SLUDGE
Nicotine (NRT)
Class: Direct acting non-ester alkaloid
Mech: Direct-acting nicotinic cholinomimetic
Thera: Smoking cessation (reduces cravings)
