Cholinergic Agonists

Question 1

Cholinergic agonists

• direct acting cholinesterases
• indirect acting reversible anticholinesterases
• indirect acting irreversible organophosphates

Answer 1

Direct acting cholinesterases

• acetylcholine
• betanechol
• carbamol
• pilocarpine

Indirect acting reversible anticholinesterases -> can provoke response in all cholinoceptors

• physostigmine
• neostigmine
• pyridostigmine
• edrophonium

Indirect acting irreversible organophosphates
- echotiophate
- isoflurophate
Reactivariam of AchE - pralidoxime

Question 2

Acetylcholine

Answer 2

Inhibitors are hemicholinium, botulin toxin, black widow spider venom.

Very short hl.
Can’t Cross Ms easily.

N and M Rs -> diffuse actions -> therapeutically not important

TU:

• decrease HR and CO
• vasodilation -> decrease BP
• increase salivary, intestinal, bronchial secretions
• increase GIT motility
• increase tone of detrusor mm (urination)
• miosis and stimulation of cilliary mm contraction -> near vision

Question 3

Bethanecol

Beth activates Bowels and Baddler

Answer 3

Not hydrolyzed by AchE -> increase hl

Strong M, little to no N Rs

TU: Stimulation of atomic bladder (in postpartum and posteoperative, nonobstructive urinary retention) and bowels

AE: wide spread cholinergic activation

Question 4

Carbamol

Carbamylcholine

Answer 4

Ester
Apply in pts intolerant to pilocarpine, for miosis, decrease iop

N and M Rs

TU:

• Rarely used except for the eye
• Effects of CVS and GIT (ganglionic stimulating activity)
• Miosis (locally to the eye) -> decrease iop

AE: rare due to lack of systemic penetration

Question 5

Pilocarpine

Answer 5

Alkaloid, tertiary amine, not hydrolyzed by AchE -> increase hl

M Rs

TU:

• ophthalmology -> rapid miosis and contraction of ciliary mm
• drug of choice in emergency to treat glaucoma (closed/open angle) to decrease iop
• xerostomia and Sjögrens

AE:

• CNS disturbances
• profuse sweating and salivation

Question 6

Physostigmine

Answer 6

Alkaloid, 3ry amine, can enter and stimulate CNS

N and M Rs in ANS, N at NMJ

TU:

• atony of bladder and GIT
• treatment of glaucoma
• overdose w/ antiAchE drugs (atropine, phenothiazines and TCAs)

AE:

• convulsions (high doses)
• bradycardia and decrease CO
• mm paralysis (if AchE inhibition is too long)

Question 7

Neostigmine

Answer 7

4ry amine, + polar -> penetrate poorly CNS, greater effect on skeletal mm -> can stimulate contractility before paralysis

TU:

• stimulation of GIT and bladder
• antidote for tubocurarine (and other competitive NM blockers)
• symptomatic treatment of Myasthenia Gravis

AE:

• widespread cholinergic stimulation
• decrease BP
• salivation, flushing, nausea, abd pain, vomiting, bronchospasm

Question 8

Pyridostigmine

Answer 8

AchE inhibitor

TU: chronic management of Myasthenia Gravis

AE:

• widespread cholinergic stimulation
• decrease BP
• salivation, flushing, nausea, abd pain, vomiting, bronchospasm

Question 9

Edrophonium

Answer 9

4ry amine

TU:

• diagnosis of MG
• similar to neostigmine, but faster absorption and slow action (hl = 10-20min)

Question 10

Tacrine
Donezepil
Rivastigmine
Galantamine

Answer 10

1st line treatment in Alzheimer’s

Question 11

Ecothiophate

Answer 11

Covalently binds to serine-OH at the active site of AchE -> enzyme is permanently inactivated and restoration of activity of AchE requires synthesis of new enzymes

TU:

• paralysis of motor functions
• convulsions
• intense miosis
• chronic treatment of open angle glaucoma

Question 12

Pralidoxime (PAM)

Answer 12

Can reactive inhibited AchE if given before aging of the alkylated enzyme, can reverse the effects except for CNS