1. Autonomic Nervous System Anticholinergic Drugs- 5
أ0م0د.وحدة بشير اليوزبكي

2. Objectives 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.

3. 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.

4. Classifications of Anticholinergic Drugs
I- Antimuscarinic Agents:
1- M1 Selective.
2- Non selective.
II- Antinicotinic Agents:
1- Ganglionic Blocking Agents.
2- Neuromuscular Blocking Agents.

5. 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.

6. 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.

7. 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. ??

8. 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)

9. Actions of Atropine 3- On CVS : Note:
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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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).

16. 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.

17. 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.

18. Contraindication of antimuscarinic drugs
1. Glaucoma ??.
2. In elderly men should be used in caution and should be avoided in those have history of prostatic hyperplasia ??.
3. peptic ulcer: Because atropine slow gastric empting , they increase symptoms in patient with.

19. The End