mpathomimetic drugs) · parasy mpathomimetic drugs) chol inomimetic drugs dr. dheeraj bisht....

( Parasympathomimetic Drugs)

( Cholinomimetic Drugs )

Dr. DHEERAJ BISHT .

Department of Pharmaceutical Sciences

Bhimtal, Kumaun Univesity, Nainital

Introduction

Pharmacological Actions

Therapeutic Uses

Pharmacotherapy of Myasthenia Gravis

✓ These are drugs which produce action similar to that of ACh,

either by directly interacting with cholinergic receptor

( Cholinergic agonist) or by increasing availability of ACh at

these sites(Anticholinesterases).

✓ Dale Principle : A mature neurons release the same

neurotransmitter at all of its synapses.

Receptor Locations Mechanism

N M Neuromuscular junction Ion channel

N N Autonomic ganglia

Adrenal medulla

CNS

Ion channel

Receptor Locations Mechanism

M 1 ANS, CNS Gq

M 2 Heart, ganglia Gi

M 3 Smooth muscle, glands,

Vascular endothelium

Gg

M 4 CNS Gi

M 5 CNS Gq

gg

Cholinergic drugs

Direct acting Indirect acting

Muscarinic Nicotinic Organophosphates

) very low acting (

Carbamates

Intermediate ( )

Edrophonium

( Short Acting )

Choline esters

Alkaloids

❖ Choline esters : Acetylcholine

Methacholine

Carbachol

Bethanechol

❖ Natural Alkaloids : Muscarine

Pilocarpine

Arecoline

❖ Synthetic Agonists : Cevemiline

Varenicline

Oxotremorine

Tremorine

ORGAN SYSTEM EFFECT/ ACTION

Central nervous system Complex stimulating effects

Autonomic nervous system Sympathetic and Parasympathetic ganglia

stimulating

Skeletal Muscle Contraction

ORGAN SYSTEM ACTIONS

EYE Sphincter pupillae

Ciliary muscle

Miosis

Cyclospasm, accomodation

of near vision

HEART SA node

Atria

AV node

Ventricles

Negative chronotropy

Negative ionotropy

Negative dromotropy

Negative ionotropy

BLOOD VESSELS Dilatation via realease of

EDRF from endothelium

(NO)

BRONCHI Bronchoconstriction

GI TRACT Motility

Sphincter

Increases peristalsis

Relaxation

URINARY BLADDER Detrusor

Trigone & Sphincter

Contraction

Relaxation

GLANDS Increases secretion

CHOLINE ESTER

Bethanechol – (Dose – 10-40 mg oral, 2.5-5mg s.c ) USES

• Postoperative/postpartum nonobstructive urinary retention, neurogenic bladder to promote urination.

Side effects-

• Sweating, Intestinal Colic, fall in BP, Bronchospasm.

Contraindication-

• Hyperthyroidism

• Bronchial asthma

• Peptic ulcer

• Myocardial infraction

• Pregnancy or breastfeeding

Pilocarpine –(Dose- 0.5 - 4% eye drops )

• It is a third line drug in open angle glaucoma.

• It is used to lower high eye pressure.

Side effects

• Sweating, salivation, increase in other secretions.

Contraindication-• Inflammation of the front portion of he eye.

• Inflammation of the cornea of the eye.

• Pupillary block glaucoma.

• Inflammation of the iris – the colored part of the eye.

• Plant alkaloid – Nicotiana tobaccum

• Fatal dose of nicotine - 40 mg

• Smoking cessation therapy: nicotine patches, chewing gums

VARENICLINE-• Partial agonist at NN receptor and α4β2

• Act on mesolimbic – Dopamine system ; reduce craving

Side effects

• Nausea

• headache

• insomnia

Anticholinesterases (anti-ChEs) are agent which inhibit ChE,

protect ACh from hydrolysis – produce cholinergic effects in

vivo and potentiate ACh both in vivo and in vitro.

ANTICHOLINESTERASES

Reversible Irreversible

Carbamates Acridine

Organophosphates Carbamates

CARBAMATES- ORGANOPHOSPHATE -

• Physostigmine (Eserine) Dyflos (DFP)

• Neostigmine Echothiophate

• Pyridostigmine Malathion*

• Edrophonium Diazinon*

• Rivastigmine Tabun`, Sarin`, soman`

• Donepezil

• Galantamine

CARBAMATES-

ACRIDINE- Carbaryl*

• Tacrine Propoxur*

* Insecticides` Nerve gases for chemical warfare

S.no Physostigmine Neostigmine

1. Source Natural Alkaloid from

Physostigma venenosum

Synthetic

2. Chemistry Tertiary amine derivative Quaternary ammonium compound

3. Oral absorption Good Poor

4. CNS action Present Absent

5. Applied to eye Penetrates cornea Poor penetration

6. Direct action on NM

cholinoceptors

Absent Present

7. Prominent effect on Autonomic effectors Skeletal muscles

8. Important use Miotic (Glucoma) Myasthenia gravis

9. Dose 0.5-1 mg oral/parental

0.1-1.0% eye drops

0.5-2.5 mg i.m/s.c

15-30 mg orally

10

.

Duration of Action Systemic 4-6 hrs

In eye 6- 24 hrs

3-4 hrs

• Myasthenia gravis is an

autoimmune disorder

Characterized by

progressive weakening of

Skeletal muscle.

• Development of antibodies

directly to the nicotinic

receptor (NR)

• Diagnosis ;

• Tensilon Test : Myasthenia crisis

Cholinergic crisis

• Treatment –

• Neostigmine (0.5-2.5 mg i.m/s.c, 15-30 mg orally)

• Pyridostigmine (60 mg orally)