parasympathomemtics

parasympathomemtic drugs

PREPARED BY DR.HEBA AL-SALEH

Start

·objectives

parasympathetic

memetic drugs

·effect

·muscurinic

·nicotinic

Index

· Comparison

drugs that memic

end

objectives

At the end of this session the student will be able to: 1. Define the meaning of mimetic drugs and lytic drugs according to the text book. 2. List the Physiological effect for direct Cholinergic agonist drugs according to the textbook. 3. List the clinical indications of direct acting cholinergic drugs and their side effects. 4. List the generic drugs for this group and the mechanism of actions, uses for each one.

01

1 st: ParaSympathomimetic Drugs:

also called : cholenegic drugs

ParaSympathomimetic Drugs:

Also referred cholinergic drugs. These sets of drugs that stimulate the PNS and lead to the effect mimicked the effect of parasympathetic nerve discharge.  Mode of action of parasympathomimetic cholinergic drugs can be either direct or indirect.

I. Direct Action Cholinergic Agonist:

The direct acting agent binds and activates muscarinic receptor and to parasympathetic effect.

Muscarinic effect:

1. Vasodilation. 2. Decrease heart rate. 3. Stimulation of gastrointestinal smooth muscle and increase peristalsis (Promote defecation). 4. Contraction of urinary bladder + relaxation of sphincter (promote urination). 5. Broncho contraction (bronchospasm). 6. Pupil constriction (miotic action). 7. Decrease intraocular pressure (In glaucoma). 8. Increase secretion (Sweat, Saliva, Gastric Juice).

nicotinic effect:

Muscarinic drugs may have some nicotinic effect in variable degrees so cause skeletal muscle contraction. Ex: Acetyl choline has strong nicotinic effect.

Clinical Indication Of Direct Acting Cholinergic: 1) Glaucoma. 2) Treatment of abdominal distension and constipation. 3) Urinary retention. 4) Treatment of Myasthenia Gravis by Stimulation of skeletal muscle. Side Effects: 1. Nausea vomitting and diarrhea. 2. Bronchoconstriction and Respiratory failure. 3. Decrease HR and BP. 4. Excessive sweating and salivation.

The Drugs:

1) Acetyl choline: (naturally occuring substances) Effect: 1. Parasympathomimetic (muscarinic effect). 2. Nicotinic effect skeletal muscle contraction → large dose cause paralysis and spasm. 3. Ganglionic effect by bind to nicotinic receptors in ganglia stimulation SNS + PNS Uses: because rapidly destroyed by Acetylcholine esterase, it has no systemic uses , and destroyed by gastric secretion if given orally.

Esters Of Choline: Carbachol: 1. Same of Acetylcholine affect muscarinic and nicotinic receptor. 2. More stable by Acetylcholine esterase. 3.Less uses because it’s stimulate the ganglia. 4. Topically, Miotic in cataract surgery. Bethanechol: Has stronger muscarinic activity for GI + GU tracts. Uses: 1. Drug of choice in treatment of gastroesophageal reflex. 2. Urinary retention. Dosage form: - Oral, subcutaneous - Should not be given IV or IM because severe muscarine effect. Side effect:  Excess saliva.  Flushing + abdominal spasm.

Alkaloids: Pilocarpine: Source: alkaloid from the Gaborandy. Effect: direct cholinergic stimulant has Muscarinic effect with little nicotinic effect. Uses: 1) It’s used in topical application in ophthalmology, drug of choice in all type of Glaucoma. 2) Less used systemically because it has no selectivity. 3) May used to ↑ salivation in dry mouth. 4) atropine antidote. Side effects:  diarrhea.  Increase body secretion tolerated by give Atropine. Dosage form: ophthalmic solution 0.25 – 10%, 1 – 6 times daily. Muscarine: Alkaloids from fungal (Amunita Muscaria) it has no clinical uses because highly toxic (more than Acetylcholine).

02

II. Indirect Acting Cholinergic Drugs (anticholinestereases):

Action: Inhibit action of Acetylcholinesteras and allow accumulation of Ach at cholinergic receptor site.

Effect: Lead to accumulation of Ach in synapses so they have muscarinic and nicotinic effect.  Increase skeletal muscle contract.  Increased parasympathetic effect.  Increase nerve conduction in the ganglia.  ↑ Ach in CNS. Uses: 1. Glaucoma. 2. Diagnosis of myasthenia gravies (Edrophonium). 3. Insecticides (organophosphates). 4. Treatment of myasthenia gravies. 5. Curare and Atropine poisoning. 6. Urinary retension and intestional distention.

There are two main categories of cholinesterase inhibitors:

1) Reversible inhibitors of Acetylcholinesterase. 2) Irreversible inhibitors of Acetyl cholinesterase.

A) Reversable Anticholinesterase:

1) Physostigmine (Eserine) : Effect: oldest anticholinesterase. Pharmacokinetics: absorbed well from GI also enter CNS. Uses: 1. Used as miosis. 2. Treatment of Glaucoma. 3. Antidote of Atropine poisoning. dosage – form: ophthalmic solution 0.25 – 0.5% tablet. 2) Neostigmine: Source: synthetic. Structure: quaternary ammonium with + ve sign. Effect: anticholinesterase. Pharmacokinetic: poorly absorbed orally not reach CNS. Uses: 1) Diagnosis of myasthenia gravis. 2) Anti – dote of curare. 3) Gastrointestinal and genitourinary paralysis (post operative). Dose: Parenteral 0.5 mg/kg

A) Reversable Anticholinesterase:

3) Pyridostigmine: Effect: Anticholinesterase that approximately one – fourth as potent as Neostigmine. Pharmacokinetics: Absorbed well from GI with long action. Uses: it’s principal use of treatment of myasthenia gravis orally – with long duration with less side effect. Dose: Orally 60 mg/4 times daily also sustained release tablet. 4) Edrophonium: Effect: Anticholinesterase. Uses: Diagnosis and treatment of myasthenia gravis.

B) Irreversible Anticholinesterase:

They inhibit acetylcholinesterase with irreversible manner these drugs characterize by a long and strong effect. The duration of action is depend on time for resynthesis of cholinesterase which takes (weeks to months) and this group usually Organophosphate  this group penetrate BBB and affect CNS.  they can also be absorbed from the skin. Uses:  These compounds used in insecticides pesticides and chemical warfare.  In very small doses used primarily as eye drop in treatment of Glaucoma.  In large doses produce cholinergic crisis, respiratory paralysis and death.  These extremely toxic drugs.

Managing the toxicity of organophosphate:

usually toxicity because of accidental exposure to toxic: 1) Antidote → Atropine may antagonize there effect, large repeated dose. P.S Atropine (anticholinergic drug). 2) Pralidoxime: Reactivate acetylcholinesterase enzyme after inhibited by irreversible inhibitors. 3) Maintenance of Respiration

effects and adverse effects

Usually because excess stimulation of PNS. 1. nausea + vomitting 2. diarrhea + excessive sweating 3. blurred vision. 4. Muscle tremor. 5. Bronchoconstriction. 6. Muscle paralyses → respiratory depression → death.

drugs :

1. Isoflurophate: Indirect cholinergic irreversible (DFP) from organophosphate. Uses: Low doses 0.025% for treatment of Glaucuma (it has long duration). 2. Echothiophate: Treatment of Glaucoma. 3. Parathion: Insecticide. 4. Malathion: Insecticide. 5. Taban Sarin: Chemical warfare.

THANKS!

for your attention