Cholinesterase Inhibitors/Myasthenia Gravis

Question 0

Reversible cholinesterase inhibitors

Answer 0

Neostigmine, other reversible cholinesterase inhibitors

Question 1

Cholinesterase Inibitors

Answer 1

Drugs that prevent the degradation of ACh by acetylcholinesterase; viewed as indirect acting cholinergic agonists
-lack sensitivity, limited therapeutic applications

Question 2

Irreversible cholinesterase inhibitors

Answer 2

Basic pharmacology, toxicology

Question 3

Neostigmine (Prostigmin)

Answer 3

Cannot readily cross membranes, absorbed poorly with oral administration, minimal effects on brain and fetus, poor substrate for cholinesterase (ChE)

Question 4

Neostigmine: Pharmacologic effects

Answer 4

Therapeutic administration: muscarinic receptors

Question 5

Neostigmine: muscarinic responses

Answer 5

Identical to muscarinic agonist response

Question 6

Neostigmine: neuromuscular effects

Answer 6

Therapeutic dose: increases force of contraction in skeletal muscle; toxic levels: decrease force of contraction

Question 7

Neostigmine: central nervous system

Answer 7

Therapeutic levels: mild stimulation, toxic levels: CNS depression

Question 8

Neostigmine: therapeutic uses

Answer 8

Myasthenia gravis; reversal of nondepolarizing neuromuscular blockade

Question 9

Neostigmine: adverse effects

Answer 9

Excessive muscarinic stimulation, neuromuscular blockade, treatment with antagonist

Question 10

Neostigmine: precautions and contraindications

Answer 10

Obstruction of GI or urinary tract, peptic ulcer disease, asthma, coronary insufficiency, hyperthyroidism

Question 11

Neostigmine: drug interactions

Answer 11

Muscarinic antagonists, nondepolarizing neuromuscular blockers, depolarizing neuromuscular blockers

Question 12

Other “reversible” cholinesterase inhibitors

Answer 12

Physostigmine, ambenonium, edrophonium, pyridostigmine, drugs for Alzheimer’s disease

Question 13

“Irreversible” cholinesterase inhibitors

Answer 13

Highly toxic, primarily used as insecticides, only clinical application is glaucoma, all contain an atom of phosphorus, almost all are highly lipid soluble, readily absorbed from several routes, potential use in chemical warfare

Question 14

Myasthenia Gravis

Answer 14

Characterized by fluctuating muscle weakness and predisposition to rapid fatigue; common symptoms: ptosis, dysphagia, weakness of skeletal muscles
-Autoimmune process in which antibodies attack nicotinic(M) receptors on skeletal muscles

Question 15

Myasthenia gravis treatment

Answer 15

Cholinesterase inhibitors; beneficial effects: increased muscle strength/side effects: excessive muscarinic response
Dosage/adjustment: start small and modify; signs of undermedication: ptosis, dysphagia vs. overmedication: excessive salivation, muscarinic respones

Question 16

Cholinergic crisis

Answer 16

Characterized by extreme muscle weakness or frank paralysis and signs of excessive muscarinic stimulation; treatment with respiratory support and atropine