Dr: Samah Gaafar Al-shaygi

1. بسم الله الرحمن الرحيم The Autonomic Nervous System (1) Dr: Samah Gaafar Al-shaygi

2. Central NS Nervous system Peripheral NS Efferent division Afferent division Autonomic NS Somatic system enteric parasympathetic sympathetic

3. Anatomy of the ANS: • Efferent neurons. • Afferent neurons.

4. Cholinergic Agonist • Ach transmission has 6 steps: • Synthesis, storage, release, binding, degradation & choline recycling.

5. Cholinergic agonist: • Direct-acting cholinergic agonist. • Indirect-acting cholinergic agonist. (anti-cholinestrase).

6. Direct-acting cholinergic agonist: • Binds directly to cholinoceptors. • Synthetic esters of choline or natural alkaloids. • Longer action than Ach. Acetylcholine: • Has no therapeutic importance due to the multiplicity of action & the rapid inactivation. • Has both muscarinic & nicotinic activity.

7. Action: • the heart rate, COP & the BP. • the GIT secretions & motility. • the bronchial secretion. • the tone of detrosur muscle. • leads to ciliary muscle contraction & pupilary constriction. Bethanechol: • Related structurally to ACH. • It has no nicotinic action but a strong muscarinic one.

8. Action: • In the GIT, it increases motility & tone. • In the bladder, it stimulates the detruser muscle causing urine expulsion ( used for PO atonic bladder). A.E: • As generalized cholinergic stimulation. Carbachol: • Muscarinic & nicotinic action.

9. Action: • On the CVS. • On the GIT. • Epinephrine release from the adrenal medulla (nicotinic action). • In the eye it causes miosis & spasm of accommodation. • is used as a miotic agent to treat glaucoma (pupilary constriction & the IOP).

10. pilocaroine: • Less potent than Ach & it’s derivatives. • Has muscarinic activity. • Used in the eye to produce miosis & accommodation spasm. • The drug of choice in emergency lowering of the IOP. A.E: • CNS disturbances. • Profuse sweating & salivation.

11. Reversible -anticholinestrase • They inhibit Ach-esterase so prolong the action of Ach. • Act on all cholinoceptors in the body (nicotinic & muscarinic).

12. Physostigmine: • A tertiary amine. • intestinal & bladder motility so is used in atony. • Used in glaucoma. • To treat overdose of anti-cholinergic action as atropine. A.E: • Convulsions. • Bradycardia & COP. • Skeletal muscle paralysis (rare with therapeutic dose).

13. Neostigmine: • A quaternary amine. • Stronger action than physo. On skeletal muscles (contraction then paralysis). • Used to stimulate the bladder & GIT, myasthenia gravis (edrophonium for Δ). A.E: • generalized cholinergic stimulation.

14. Irreversible anticholinesterase • Are synthetic organophosphorus compound. • Extremely toxic (as pesticides). Isoflurophate: • Generalized cholinergic stimulation. • Paralysis of motor function (breathing difficulties). • Convulsions. • Intense miosis (topically to treat open-angle glaucoma) ecothiophate replace it. • Pralidoxime is an antidote (except for the CNS).

15. Cholinergic antagonists1-Antimuscarinic • They block the muscarinic receptors inhibiting their function. Atropine: • Binds competitively. • Acts centrally & peripherally. Action: • In the eye it causes persistent mydriasis & cycloplegia. • GIT : it’s an antispasmodic.

16. Urinary system: it decrease the bladder motility. • CVS: In low dose bradycardia (blocks M1 in the inhibitory prejunctional neurons. In higher doses HR (blocks M2 in SA node). • It blocks the salivary, lacrimal & sweat glands (as antiscretory prior to surgery). • Used as an antidote for cholinergic agonist.

17. A.E: • Tachycardia, dry mouth, constipation, blurred vision, restlessness, confusion hallucinations & glaucoma precipitation. Scopalamine: • It has greater CNS action, longer duration, anti-motion sickness, sedation & blocks short term memory. Ipratropium: • Quaternary derivative of atropine & is positively charged. • As an inhaler in asthma & COPD.

18. Ganglionic Blockers • Work on the nicotinic receptors in the autonomic ganglia. • Are non-depolarizing competitive blockers. • Has no selectivity for sympathetic or parasympathetic ganglia (so rarely used therapeutically only experimentally). Nicotine: • Stimulation & then paralysis of all the ganglia. • It causes transmitter release. • It BP, HR, secretions & peristalsis. • At higher doses the opposite happens due to ganglionic block.

19. Trimethophan short acting, used as an alternative drug to lower the BP in emergency situations. Neuromuscular blocking drugs: • Either antagonist (non-depolarizing), or agonist (depolarizing). Non-depolarizing (competitive) blockers: • At low dose they compete with Ach & prevent muscle contraction (action is overcomed by e.g. cholinesterase inhibitors).

20. At high doses, they can block the ion-channels so further weakening the NMJ transmission. • Used in surgery for muscle relaxation. • They don’t cross the BBB. • A.E: release of histamine, BP& HR, malignant hyperthermia, hyperkalemia. • Drug interactions: • Cholinesterase inhibitors overcome the action. • Halothane stabilizes their action. • Aminoglycosides antibiotics enhance the blockade by inhibiting Ach release. • Calcium -channel blockers may enhance their action.

21. Depolarizing agents: • Act as ach, they depolarize the receptors. • The sustained depolarization renders the receptor unable to transmit further impulses, so gradual repolarization. • E.g. is succinylcholine, has a rapid onset & short duration of action so used in anesthesia & in ECT. A.E: hyperthermia & apnea.

22. THANK YOU