Exam 1 Drugs: Anti-ChEs (12)

Question 1

Edrophonium

Answer 1

• reversible inhibitor, binds to choline subsite
• short & rapid onset (2-10 mins)
• used in diagnosis of Myasthenia Gravis, Eaton-Lambert Syndrome, and disorders leading to muscle weakness
• adverse: seizures, bronchospasms, cardiac arrhythmia, brady, cardiac arrest (all serious) also hypo or hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
• Contra: mech. intestinal or urinary obstruction, choline ester or depolarizing neuromuscular-blocker use, CV disease

Question 2

Neostigmine

Answer 2

• Quaternary, reversible carbamoyl ester linkage
• direct cholinergic agonist effects @ Nm receptors*
• injected dosage more effective than oral
• used for CHRONIC treatment of Myasthenia Gravis and other NMJ diseases; urinary or GI motility (post-op); glaucoma
• lower part of esophagus also stimed*
• makes skeletal muscle paralysis by succinylcholine WORSE*
• adverse: seizures, bronchospasms, cardiac arrythmia, brady, cardiac arrest (all serious), also hypo or hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
• contra: mech. instestinal or urinary obstruction, choline ester or depolarizing NMJ blocker use, CV disease

Question 3

Pyridostigmine

Answer 3

• Reversible carbamoyl ester linkage
• oral or parenteral dosage
• used for CHRONIC treatment of Myasthenia Gravis and other NMJ; urinary or GI motility (post-op); glaucoma
• also used to pretreat nerve gases*
• adverse: seizures, bronchospasm, cardiac arrhythmia, cardiac arrest, brady (all serious), also hypo or hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
• contra: mech. intestinal or urinary obstruction, choline ester or depolarizing NMJ blocker use, CV disease

Question 4

Ambenonium

Answer 4

• reversible carbamoyl ester linkage
• oral dosage
• used for CHRONIC treatment of Myasthenia Gravis and other NMJ; urinary or GI motility (post-op); glaucoma
• adverse: seizures, bronchospasm, brady, cardiac arrest, cardiac arrhythmia (all serious), also hypo and hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
• contra: mechanical obstruction of GI or urinary tract, CV disease, also taking choline ester or depolarizing NMJ blocker use

Question 5

Physostigmine

Answer 5

• tertiary reversible carbamoyl ester
• used to combat CNA anticholinergic toxicity and reversal of induced paralysis in surgery
• adverse: seizures, bronchospasm, brady, cardiac arrythmia, cardiac arrest (all serious), also hypo or hypertension, salivation, lacrimation, diaphoresis, vomiting, diarrhea, miosis
• contra: CV disease, taking nmj blockers or cholinergics, obstruction of GI or urinary tract

Question 6

Tacrine

Answer 6

• crosses BBB, oral dosage
• used treatment of mild to moderate Alzheimer’s/ dementia
• adverse (all common): diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams
• contra: treatment-associated liver function test abnormalities
• 30% have reversible hepatotoxicity within 3 months*
• modest symptomatic benefits in Alzheimer’s disease

Question 7

Donepezil

Answer 7

• crosses BBB, oral dosage
• used in treatment of mild to moderate Alzheimer’s/ dementia
• adverse (all common): diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams
• NO CONTRA*
• modest symptomatic benefits in Alzheimer’s

Question 8

Rivastigmine

Answer 8

• Carbamoyl, cross BBB, oral dosage
• used in treatment of mild to moderate Alzheimer’s/dementia
• adverse (all common): diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams
• NO CONTRA*
• modest symptomatic benefits in Alzheimer’s
• affects both Anti-ChE and butylcholinesterases by forming a carbamoylate complex with the enzymes

Question 9

Galantamine

Answer 9

• Oral dosage, cross BBB
• used for treatment of mild to moderate Alzheimer’s/ dementia
• also acts as non-potentiating ligands of nicotinic receptors*
• adverse (all common): diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams
• NO CONTRA*

Question 10

Echothiophate

Answer 10

• only organophos used clinically*
• quaternary, non-volitale, does not penetrate skin
• used in treatment of advance, open-angle glaucoma
• may be associated with production of cataracts
• adverse: brow ache, uveitis, blurred vision
• contra: active uveal inflammation, closed angle glaucoma
• long acting*
• largely replaced by better agents

Question 11

Demecarium

Answer 11

• used for treatment of open-angle glaucoma; induces miosis
• two neostigmine molec connected by 10 methylene groups*
• adverse: hypersensitivity, abdominal cramps or diarrhea (all serious), also stinging, burning or red eyes, headache, brow ache, decreased night vision
• contra: pregnancy, active uveal inflammation, angle-closure glaucoma

Question 12

Pralidoxime

Answer 12

• 2-PAM
• treatment for acute intoxication from Anti-ChEs
• cholinesterase REACTIVATOR
• early treatment before aging very important
• treat also with atropine a week or longer