Cholinergic Drugs PharmD 23-24 PDF

Cholinomimetics (Cholinergic) drugs 7 Direct-acting cholinergic agonists Agents include choline esters Drug PK/Indications Rapidly hydrolyzed by cholinesterase (ChE); Acetylcholine duration of action 5–30 s; poor lipid solubility - Resistant to ChE; orally active, poor lipid Carbachol Bethanec...

Cholinomimetics (Cholinergic) drugs 7 Direct-acting cholinergic agonists Agents include choline esters Drug PK/Indications Rapidly hydrolyzed by cholinesterase (ChE); Acetylcholine duration of action 5–30 s; poor lipid solubility - Resistant to ChE; orally active, poor lipid Carbachol Bethanechol solubility; duration of action 30 min to 2 h - ↑ the aqueous outflow and ↓ the intraocular tension in open-angle glaucoma. use as a miotic in surgery - Resistant to ChE; orally active, poor lipid solubility; duration of action 30 min to 2 h - acute postoperative and postpartum non-obstructive urinary retention 11 Direct-acting cholinergic agonists Alkaloids Drug PK/Indications -Not an ester, good lipid solubility; duration of action 30 min to 2 h Pilocarpine - ↑ the aqueous outflow and ↓ the intra(Ophthalmic ocular tension in open-angle glaucoma. eye drops) - off label to counter the effects of cycloplegics Cevimeline Xerostomia Nicotine Not an ester; duration of action 1–6 h; high lipid solubility Partial agonist at N receptors, high lipid solubility; Varenicline duration 12–24 h 12 Cholinergic medications ▪ Indirect-acting cholinergic agents increase the availability of acetylcholine at the cholinergic receptors. 13 MOA of indirect cholinergic agonist 14 Indirect-acting cholinergic agonists Reversible Drug Indications Edrophonium - Alcohol, quaternary amine, poor lipid solubility, not orally active; duration of action 5–15 min Tensilon test* (no longer used) - Neostigmine preceded by atropine to block muscarinic effects, rapidly Neostigmine reverses muscle paralysis induced by (Transdermal) neuromuscular blockers - prevention and treatment of urinary (Ophthalmic distention and retention eye drops) - Snakebite - Off-label use in acute colonic pseudoobstruction 15 Indirect-acting cholinergic agonists Reversible Drug PK/Indications - Carbamate, quaternary amine, poor lipid Physostigmine Pyridostigmine (PO, parenteral) solubility, orally active; duration of action 30 min to 2 h or more (& Neostigmine) - is the specific antidote for poisoning with belladonna or other anticholinergics* - Carbamate, like neostigmine, but longer duration of action (4–8 h) - Myasthenia gravis *It should only be used to reverse toxic, life-threatening delirium caused by an anticholinergic agent (atropine, scopolamine, diphenhydramine). 16 Indirect-acting cholinergic agonists Reversible used for AD (ACHEIs) Drug Indications Donepezil (PO) Galantamine (PO) Rivastigmine Dementia of all types. From mild to moderate Alzheimer disease and in some cases of PD. (PO) 17 Indirect-acting cholinergic agonists Irreversible Drug PK Information Ecothiophate Organophosphate*, moderate lipid solubility; duration of action 2–7 days Parathion Organophosphate*, high lipid solubility; duration of action 7–30 days; insecticide Sarin Organophosphate*, very high lipid solubility, nerve gas *Get absorbed from all sites, including intact skin and lungs. 18 AEs of Cholinomimetics 22 Take-home message 1. Cholinergic agonists stimulate the parasympathetic nerves, some nerves in the brain, and the neuromuscular junction at the same site that ACh does. 2. Cholinergic agonists are used topically in the eye to produce miosis (pupillary constriction) and treat glaucoma. 3. Systemically, these agents are used to increase bladder tone (e.g., postoperative or postpartum) and to increase secretions to relieve dry mouth associated with Sjögren syndrome. 23 Enhancing Healthcare Team Outcomes 1. Healthcare workers, including pharmacists and nurses, need to be aware of the common adverse effects of cholinergic medications. 2. Patients who are on a cholinesterase inhibitor should be seen for follow-up at three and six months to assess drug response, tolerance, and to prevent any symptoms of cholinergic excess. 3. Stringent measures should be in place for agricultural employers to avoid accidental exposure to insecticides with cholinergic properties. 4. Upon establishing a baseline, periodic blood tests should be done to check cholinesterase concentrations. Timely intervention can help prevent cases of overexposure and poisoning. 24 Enhancing Healthcare Team Outcomes 5. Pharmacists should be trained and have easy access to drug intoxication procedures at all institutions receiving presentations of intoxication. 6. Patients should receive education, in detail, regarding the common potential adverse effects of all new medications. 7. When prescribing cholinergic drugs, an interprofessional team approach is essential. 8. A pharmacist consult is beneficial; the pharmacist can verify dosing, look for drug-drug interactions, and perform medication reconciliation, and report back to the prescriber if there are issues. 25