Pharmacology: Katzung Cholinoreceptor-activating and Cholinesterase-inhibiting drugs Flashcards
What is the fundamental mechanism behind the direct acting cholinomimetic drugs?
Direct acting cholinomimetics are muscarinic and nicotinic agonists.
What is the fundamental mechanism behind the indirect acting cholinomimetic drugs?
The indirect acting cholinomimetc drugs are cholinesterase inhibitors that prevent the breakdown of ACh in the synaptic cleft.
What class of drugs are acetylcholine, bethanechol, Carbachol, pilocarpine, nicotine, and varenicline?
They are direct acting cholinomimetics.
Which direct acting cholinomimetics act on both muscarinic or Nicotinic receptors?
Acetylcholine and Carbachol
Which direct acting cholinomimetics act preferentially on muscarinic receptors?
Bethanechol and pilocarpine
Which direct acting cholinomimetics act preferentially on nicotinic receptors?
nicotine and varenicline
What is the molecular mechanism behind M1 and M3 receptors?
Receptor activation stimulates Gq proteins which increase IP3 and evoke the release of calcium from intracellular stores. The result is smooth muscle contraction.
What is the molecular mechanisms behind M2 receptor action?
Some M2 receptors are coupled to Gi proteins which decrease cAMP. others are linked to potassium channels where they facilitate K+ outflow..
What is the molecular mechanism behind nicotinic receptors?
Nicotinic receptors are linked to ion channels that are selective for Na+ and K+. Stimulation of the receptors causes opening of the receptors and depolarization of the cell. This creates an excitatory post synaptic potential.
What are the CNS effects of Cholinomimetics?
Complex stimulatory effects altered mood addiction alertness convulsions possible coma
What are the effects of cholinomimetics on the eye?
contraction of the iris (miosis)
contraction of the ciliary muscle (accommodation for near vision)
cyclospasm.
What are the effects of cholinomimetics on the heart?
(1) decrease in heart rate (SA node) However there is a powerful compensatory response.
(2) Decrease in contractile force and refractory period of the atria
(3) decrease in conduction velocity and increased refractory period for the AV node
(4) small decrease in ventricular contractile force.
What is the effect of cholinomimetics on the blood vessels?
Dilation via release of endothelium derived relaxing factor.
What is the effect of cholinomimetics on the bronchi?
bronchoconstriction
What is the effect of cholinomimetics on the GI system?
Increase in smooth muscle contraction (increased peristalsis)
Decrease in tone and relaxation of sphincters.
What is the effect of cholinomimetics on the urinary bladder?
Increase in contraction of the detrusor.
Relaxation of the trigone and sphincter for voiding.
What is the effect of cholinomimetics on skeletal muscle?
Contraction of skeletal muscle.
What is the effect of cholinomimetics on the exocrine glands?
increased secretion.
What sort of toxicity is seen with muscarinic cholinomimetics?
cholinomimetic toxicity is related to excessive amounts of its normal effects.
What toxicity is seen with nicotinic cholinomimetics?
Ganglionis stimulation and block.
Muscle fasiculations and paralysis.
convulsions
depression.
What are the two principle classes of indirect acting cholinomimetics?
Carbamic acid esters
Phosphoric acid esters
There is also edrophonium and alcohol
What kind of drugs are Edrophonium, Neostigmine, Physostigmine, pyridostigmine, Echothiophate, and parathion?
These drugs are indirect acting cholinomimetics (cholinesterase inhibitors).
Which indirect acting cholinomimetic is an alcohol?
edrophonium
Which indirect acting cholinomimetics are carbamates?
Neostigmine
Physostigmine
pyridostigmine
Which indirect acting cholinomimetics are organophosphates?
Echothiophate
parathion.
What is the mechanism of action of the indirect acting cholinomimetics?
They bind to cholinesterase which then cleaves them. The alcohol portion of the cleaved molecule is released however the acidic portion remains fixed to cholinesterase thus preventing further cholinesterase action for a period of time.
Which is longer acting the organophosphates or the carbamates?
The organophosphates are longer lasting (days to weeks) than the carbamates (2-8 hours). This is because the cholinesterase eventually releases the acidic portion of the carbamate but does not release the organophosphates (thus more cholinesterase must be synthesized).
What are the effects of Cholinesterase inhibitors?
Similar by organ system to direct acting cholinomimetics. However, they do not effect uninnervated receptors like the ones found in vascular endothelium.
What are some clinical uses for direct acting cholinomimetics?
(1) glaucoma (pilocarpine)
(2) Sjogren’s syndrome (pilocarpine)
(3) Loss of normal PNS activity in the bowel or bladder (Bethanechol)
(4) Smoking cessation (nicotinic only)(verenicline)(or nicotine)
(5) Skeletal muscle paralysis (nicotinic agonists) (succinylcholine)
What significant toxicity results from parathion?
Parathion is found in insecticides and can be fatal in high enough doses.
What is the first choice antidote for cholinesterase (parathion) toxicity?
The anti-muscarinic atropine is the first choice antidote. However, this will not reverse the nicotinic toxicity. Pralidoxime must be used to remove organophosphates from cholinesterase.
What is the mnemonic for toxicity from cholinesterase inhibitors?
DUMBELSS
diarrhea urination miosis bronchoconstriction bradycardia excitation lacrimation salivation sweating
