Dr: Samah Gaafar Al-shaygi

الرحيم الرحمن الله بسم

Nervous system

Peripheral NS Central NS

Afferent divisionEfferent division

Somatic systemAutonomic NS

enteric

parasympathetic

sympathetic

Anatomy of the ANS: Efferent neurons. Afferent neurons.

Cholinergic Agonist Ach transmission has 6 steps: Synthesis, storage, release, binding,

degradation & choline recycling.

Cholinergic agonist:

1. Direct-acting cholinergic agonist.

2. Indirect-acting cholinergic agonist. (anti-cholinestrase).

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.

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.

Action:1. In the GIT, it increases motility & tone.2. 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.

Action:1. On the CVS.2. On the GIT.3. Epinephrine release from the adrenal

medulla (nicotinic action).4. In the eye it causes miosis & spasm of

accommodation. is used as a miotic agent to treat

glaucoma (pupilary constriction & the IOP).

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.

Reversible -anticholinestrase They inhibit Ach-esterase so prolong the

action of Ach. Act on all cholinoceptors in the body

(nicotinic & muscarinic).

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:1. Convulsions.2. Bradycardia & COP.3. Skeletal muscle paralysis (rare with

therapeutic dose).

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.

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).

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.

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.

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.

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.

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).

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:1. Cholinesterase inhibitors overcome the action.2. Halothane stabilizes their action.3. Aminoglycosides antibiotics enhance the

blockade by inhibiting Ach release.4. Calcium -channel blockers may enhance their

action.

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.