Cholinergic Drugs PharmD 23-24 PDF

PharmD Program Pharmaceutical Sciences Department Cholinergic Agonists Chapter 4 Principles of Pharmacology (PHM312 ) Beisan Mohammad, PhD Pharmacology 1st semester 2023/2024 Jeddah-KSA ▪ List the classes of cholinergic drugs with examples for each class. ▪ Discuss direct and indirect cholinergi...

PharmD Program Pharmaceutical Sciences Department Cholinergic Agonists Chapter 4 Principles of Pharmacology (PHM312 ) Beisan Mohammad, PhD Pharmacology 1st semester 2023/2024 Jeddah-KSA ▪ List the classes of cholinergic drugs with examples for each class. ▪ Discuss direct and indirect cholinergic drugs MOA, ADR and uses. ▪ Describe the indications and contraindications of cholinergic drugs. ▪ Explain the implications of pharmacists in cholinergic drugs use. 2 Organization of the nervous system The nervous system is divided into: 1. The central Nervous system (CNS, brain & spinal cord) 2. The peripheral nervous system (PNS, the efferent and afferent divisions) The efferent division is divided into: 1. Somatic system 2. Autonomic system (ANS, enteric, parasympathetic and sympathetic). 3 Organization of the Nervous System 4 Actions of sympathetic and parasympathetic nervous systems on effector organs. 5 Classes of ANS Drugs Types of drugs used to treat disorders of the ANS Cholinergic Drugs Anticholinergic Drugs Adrenergic Drugs Adrenergic Blocking Drugs 6 Cholinomimetics (Cholinergic) drugs 7 Synthesis and release of ACh 8 Cholinergic Medications ▪ Pharmaceutical agents that act upon the neurotransmitter acetylcholine (the primary neurotransmitter within the PNS)*. ▪ There are two broad categories of cholinergic drugs: 1. direct-acting 2. indirect-acting. *The use of cholinergic agonists has limitations because of their tendency to cause adverse effects in any organ under the control of the parasympathetic nervous system. 9 Cholinergic medications ▪ The direct-acting cholinergic agonists work by directly binding to and activating the muscarinic receptors. 10 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 Cholinomimetics spectrum of action 19 Summary of Cholinomimetics indications Myasthenia gravis Snakebite Ophthalmology acute colonic pseudoobstruction Reversal of nondepolarizing neuromuscular blockade after surgery Xerostomia Postoperative urinary retention Anticholinergic overdose Neurogenic bladder Tensilon test* Dementia 20 Contraindications of Cholinomimetics Pulmonary disease (COPD/bronchial asthma) Coronary vascular disease Peptic ulcer disease (may use with caution) Arrhythmias (atrial fibrillation) Angle-closure glaucoma Hyperthyroidism Intestinal resection or anastomosis Urinary obstruction Orthostatic hypotension Severe miosis 21 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 Questions for discussion Q1: “When prescribing cholinergic drugs, an interprofessional team approach is essential.” Define Interprofessional team approach Mention the professions included in such team Explain the importance of this approach. Q2: Explain the use of Cholinomimetics during life span. Q3: Mention the indications of the following drugs: Pilocarpine, carbachol, donepezil 26 References ▪ https://www.ncbi.nlm.nih.gov/books/NB K538163/ ▪ Chapter 4 ▪ Chapter 7 27 28