5.2 Flashcards
What are the side affects f muscarinic agonists?
Diaphoresis N/V/D Tightness in bladder Difficulty in visual accommodation Hypotension
What do magic mushrooms effect?
Muscarinic receptors!
What is pilocarpine used for?
Extracted from a South American shrubs – 1875
Genus Pilocarpus
Natives chew leaves to stimulate salivation
Action – partial agonist at muscarinic receptors (primarily)
Sweat glands are very sensitive to pilocarpine
What is Salagen used for?
Xerostomia (dry mouth)–Sjogren syndrome or head neck radiation ease swallowing
What is isopto carbine used for?
Glaucoma
Miotic agent mydriasis reversal
(muscarinic agonist)
What is Cevimeline (Evoxac®) used for?
Indications: enhances lacrimal secretions in Sjogren’s syndrome
Muscarinic agonist – high affinity for M3
Lacrimal and salivary glands
Long lasting sialogogic action
Fewer SE than pilocarpine
What is arecoline?
From Areca or Betel nuts Consumed as a euphoretic No therapeutic use Edible lime + betel nut + piper betel leaves Muscarinic agonist
How can nicotine be used clinically?
Smoking cessation; direct-activing on nicotinic receptors
What is lobeline?
Plant derivative – “Indian tobacco”
Smoking cessation
Mixed agonist-antagonist at Nicotinic receptor
What is the difference in pharmacokinetics between tertiary and quaternary amines?
Tertiary can cross the blood-brain barrier
What are the major systems impacted by muscarinic agonists?
CV- decrease HR, pumping power
GI- increase motility
Bladder- void
Eye- constrict
What happens with prolonged cholinomimetic agonist stimulation?
Post-ganglionic neurons stop firing –> muscle relaxation
Prevents electrical recovery = “depolarizing blockade”
What is an indirect-acting cholinomimetic?
AChE inhibitors
What are the types of AChE inhibitors??
Carbamic acid esters + quaternary/tertiary ammonium group Reversible inhibition Simple alcohol + quaternary ammonium Reversible inhibition Organic derivatives of phosphoric acid May be irreversible
What are Donepizil and galantamine?
Reversible AchE inhibitor- Do not act on receptor, but block breakdown of Ach, letting more Ach carry out its actions
What is neostigmine? Function?
AChE Inhibitor
Bloxiverz – reversal of non-depolarizing neuromuscular blocking agents (reversal of drug induced muscle paralysis – i.e. Atracurium (Tracrium®), Rocuronium (Zemuron®), Vecuronium (Norcuron®)…)
Urinary retention treatment and prophylaxis
Myasthenia gravis
Some direct nicotinic and muscarinic agonist effect
What is pheostigmine? Function?
AChE inhibitor
reversal of non-depolarizing neuromuscular blocking agents (unapproved)
Treat Anticholinergic toxicity
How does a depolarizing paralytic work?
Sux- Imitates Ach; binds to receptors causes depolarization = Na+ in, muscles fire, then muscle becomes refractory to stimulus
NMJ- depolarized, stays refractory
How does a non-depolarizing paralytic work?
Binds to receptor, and blocks entrance of Na+ into cells, this prevents depolarization, cell membrane stays at resting voltage
=Competitive inhibition
What is the mechanism of organophosphates?
AChE Inhibitors
How are organophosphates absorbed and distributed in the body?
Well absorbed from skin, lung, gut, and conjunctiva (except echothiophate)
Widely distributed in body – CNS
What are the CNS effects of organophosphates at low/high concentrations?
Low- alerting response
High- convulsions, coma, death
What are the smooth muscle effects of organophosphates?
Contraction
What are the effects of organophosphates at low/high concentrations on skeletal muscles?
Low: Inhibit AchE –> increase ACh –> increase strength of contraction
High: fibrillation and fasciculation
How to remember the toxicity of organophosphates?
SLUDGEM Salivation Lacrimation Urination Deification Gastric hyper motility Emesis Miosis
Tx for organophosphates? Rationale?
Atropine.
= too much PNS, need some SNS action
What is Pralidoxime (2-PAM)?
AChE reactivator
Binds to the receptor organophosphate got expelled from its binding site regenerate functional receptor
Used for nerve attacks. Not effective against neostigmine, physostigmine, or carbaryl
