Indirect-acting cholinomemetics

Question 1

Indirect-acting cholinomimetics

Answer 1

• mechanisms of action = inhibiting AChE reversibly or irreversibly –> increase of concentration of ACh
• Reversible inhibitors are used in therapeutics
• irreversible inhibitors are used as insecticides (poisoning)

Question 2

Edrophonium

Answer 2

• Short-acting
• USES:

–> Diagnosis of MG: if given Edrophonium, the patient will see dramatic improvement of symtpoms of MG, but not seen in other disorders (cholinergic crisis)

Question 3

Neostigmine or Pyridostigmine

Answer 3

• Quarternary amines (NO CNS ENTRY)
• Intermediate-acting
• USES:

–> Used in the treatment of Myasthenia gravis (MG) because the drug acts peripherally

–> Neostigmine is pregerred in the treatment of paralytic ileus and urinary retention (make sure there is NO OBSTRUCTION)

Question 4

Physostigmine

Answer 4

• tertiary amine –> ENTERS CNS
• intermediate-acting
• USES:

–> used in the treatment of glaucoma (open canal of schlemm and allow better drainage of aqueous humor inorder to releave intraocular pressure)

–> Antidote in atropine overdose

Question 5

Donepezil (tacrine)

Answer 5

• lipid-soluble (CNS ENTRY)
• USES:

–> treatment of alzheimer disease (AChE Inhibitors are used to increase concentration of cholinergic NT in the CNS)

Question 6

Organophosphates

Answer 6

• IRREVERSIBLE INHIBITORS of AChE
• LIPID-SOLUBLE, LONG ACTING
• USES:

–> INSECTICIDES (malathion, parathion

–> NERVE GASES

Question 7

Symtpoms of AChE inhibitor intoxication

Answer 7

• D = DIARRHEA (GI PANS activity = increased secretion/contraction of GI smooth muscles)
• U = uncontroled URINATION (contraction of detrusor)
• M = MIOSIS (constiction of sphincter in eye)
• B = BRONCHIOLAR constriction (lungs)
• B = BRADYCARDIA, decreased contracitlity (heart)
• E = EXCITEMENT, convulsions, coma (CNS)
• L = LACRIMATION (glands)
• S = SWEATING (sweat glands)
• S = SALVATION (saliva glands)

**OVERACTIVITY OF ACETYLCHOLINE IN SYNAPSE**

Question 8

Management of AChE inhibitor intoxication

Answer 8

• Supportive measures = terminate exposure, airway maintanence, oxygen delivery, treatment of shock, anti-convulsion therapy
• ATROPINE = antagonize the actions of muscarinic receptor sites

–> Relieves increased tracheobronchial and salivary secretions, bonchoconstriction, bradycardia, peripheral ganglionic and central actions of anti-AChE

• Reactivation of AChE via PRALIDOXIM (2-PAM)

–>function by dephosphorylating AChE leaving the function compound