Autonomic Nervous System Anticholinergic Drugs- 5
أ0م0د.وحدة بشير اليوزبكيObjectives
At end of this lecture, the students should be able to: 1- Identify the anticholinergic drugs. 2- State the classifications of anticholinergic drugs. 3- Identify antimuscarinic drugs. 4- State the pharmacokinetic of antimuscarinic drugs . 5- Discuss the mechanism of action of atropine. 6- Enumerate clinical indications of the antimuscarinic drugs. 7- Enumerate adverse effect of the antimuscarinic drugs. 9- Identify the contraindication of the antimuscarinic drugs. - At a level consistence with standards scientific curriculum for the College of Medicine/ University of Mosul.Anticholinergic Drugs
Cholinergic Antagonists, Cholinergic Blockers, Parasympatholyic Agents - These bind to cholinoceptors but do not trigger the usual receptor mediated intracellular effects. - In contrast to cholinergic agonists which have limited usefulness therapeutically, the cholinergic blockers are beneficial in a variety of clinical situations.Classifications of Anticholinergic Drugs
I- Antimuscarinic Agents: 1- M1 Selective. 2- Non selective. II- Antinicotinic Agents: 1- Ganglionic Blocking Agents. 2- Neuromuscular Blocking Agents.
Antimuscarinic drugs are divided into
I- Tertiary amine: Alkaloid esters of tropic acid. 1- Atropine: is found in the plant (Atropa belladonna). prototype. 2- Hemoatropine: Semi synthetic. 3- Scopolamine. II- quaternary amine: Semi synthetic & synthetic. - They have been developed to produce more peripheral effects with decrease CNS effect. Include: Propantheline , Ipratropium , Clidinium bromide.Pharmacokinetic of antimuscarinic drugs
- They are absorbed from GIT, mucus membrane , skin and eye . - Belladonna alkaloid cross blood brain barrier (BBB) . - Scopolamine has greater effect on CNS & eye than atropine. - Atropine has greater effect on heart, intestine, bronchi and urinary tissue than scopolamine when absorbed. - Its general actions last about 4 hours except when placed topically in the eye, where the action may last for days.Antimuscarinic Drugs Atropine
Mechanism of Action of Atropine: - Atropine has a high affinity for muscarinic receptors, where it binds competitively & reversiblely,preventing Ach from binding to that site. - It is stimulating or depressing depend on target organs and dose. Also depend on disease. - Atropine is both a central and peripheral muscarinic blocker. Notes: - Atropine opposes the effects of all cholinergic drug on the CNS, at postganglionic cholinergic N-endings & on the peripheral blood vessels. - It does not oppose cholinergic effects at the N-m junction or significantly at the autonomic ganglia. ??Actions of Atropine
1- CNS: Normal dose has minimal stimulant effect and slow sedation. 2- On eye : a- Mydriasis (dilated pupil): By blocking the MR in papillary muscle. b- Cycloplegia: By weakening the contraction of ciliary muscle , so causing loss of ability to accommodate for near vision. c- Reduction of lachrymal secretion, causing dry or sandy eyes. d- Increase intraocular pressure (IOP) ? ?(serious in elderly)Actions of Atropine
3- On CVS : In general atropine block the cardiac receptors on the SA node so the cardiac rate increases modestly (tachycardia). Note: *Atropine has no significant effect on peripheral blood vessels in therapeutic dose but with poisoning, there is marked vasodilatation.Actions of Atropine
4- On Respiratory : bronchial dilatation , decrease secretion. 5- Gastrointestinal (GlT): a- Antispasmodic due to reduction of GIT motility. b- Block salivary glands secretion drying of oral mucosa (xerostomia). 6- On GUT: smooth muscles of ureter and bladder wall are relaxed and urination is slowed. 7- Exocrine glands secretions: All decrease (except Milk) dry mouth, dry eyes, dry skin (inhibit sweating), bronchial secretion decrease & become viscid.Poisoning with Atropine
Features: - Dry mouth with dysphasia. - Mydriasis, blurred vision. - Hot flushes , dry skin with hyperthermia (CNS effect - absence of sweating). - Restlessness ,anxiety, excitement hallucinations, delirium, mania. - The cerebral excitation is followed by depression and coma. Treatment: - By giving activated charcoal to adsorb the drug. - Diazepam is given for excitement.
Clinical uses of antimuscarinic drugs
1. On CNS: a- Benzhexol ,orpheradrine, against rigidity and tremor in parkinsonism. b- Hyoscine, promethazine: used as antiemetic. c- Hyoscine prevent or reduce motion sickness. 2. Ophthalmologic disorders: - Antimuscarinic (Atropine, Homotropine,) : used in cases that need mydriasis with cycloplagia or prolonged action . -Tropicamide is the short acting mydriatic drug.Clinical uses of antimuscarinic agents
3. Respiratory disorder : a. Preoperative: To decrease bronchial secretion & spasm by preanesthetic injection of atropine or scopolamine Note: Scopolamine cause amnesia for events associated with surgery. b- Ipratropium is useful in the treatment of asthma and COAD in patients unable to take adrenergic agonists.Clinical uses of antimuscarinic agents
4. CVS disorders: - Atropine used parenterally in :- a. Myocardial infarction (MI) because it block reflex vagal stimulation (bradycardia) accompany pain of inferior MI . b. Atropine used to treat sinus bradycardia and particularly useful when the arrhythmias result from anesthetic succinylcholine.Clinical uses of antimuscarinic agents
5. GIT disturbances: a. Propantheline (Duspataline): used as antispasmodic for the treatment of spastic condition of the GIT like irritable bowel syndrome (IBS) because it lead to relaxation of smooth muscle. - Hyosine butyl bromide (Buscopan): effective relaxant of the sm.m . b- Peptic ulcer : M1 inhibitor (Pirenzepine). c- In preanesthesia: they reduce salivation and gastric secretion. d- Hyoscine, promethazine: used as antiemetic. e. Clidinium bromide: it is derivative of belladonna alkaloid used in treatment of gastric disorders. - Sometimes combine with chlordiazepoxide ( called librax).Clinical uses of antimuscarinic agents
6. Urinary disorders: - Flavoxate, propantheline and oxybutynin, are used to relieve m-spasm accompanying infection in cystitis and for detrusor instability. 7. Atropine used as antidotes to cholinergic and anticholinesterase agent, it is drug of choice to treat poisoning from organophosphate pesticides. - Its also used to block muscarinic effects due to cholinergic drugs such a neostigmine are used.Adverse effects of antimuscarinic drugs
In the infants even ordinary dose could result in antimuscarinic fever, while in adults it depends on the dose : 1. Small dose: decrease salivation , decreased bronchial secretion, decrease sweating . 2. medium dose: pupil dilation visual accommodation decreased and heart rate is increased . 3. Largest dose: inhibition to the urination and intestinal motility and this is followed by decrease in gastric section and motility . 4. over dose: all above are exaggerated , with CNS excitation , restlessness , irritability and hallucination.