CHOLINERGIC DRUGS

Cholinergic drugs are also called parasympathomimetics because their effect mimics the effect
of parasympathetic nerve stimulation. Administration of these drugs will result in an increase in
the parasympathetic activities in the systems innervated by cholinergic nerves.
There are two groups of cholinergic drugs:

1. Direct-acting: bind to and activate muscarinic or nicotinic receptors (mostly both) and
   include the following subgroups:
   a. Esters of choline: methacholine, carbachol, betanechol
   b. Cholinergic alkaloids: pilocarpine, muscarine, arecoline, nicotine
2. Indirect-acting: inhibit the action of acetylcholinesterase enzyme
   a. Reversible: neostigmine, physostigmine, edrophonium
   b. Irreversible: Organophosphate compounds; echothiophate
   The actions of acetylcholine may be divided into two main groups: –
3. Nicotinic actions- those produced by stimulation of all autonomic ganglia and the
   neuromuscular junction
4. Muscarinic actions- those produced at postganglionic cholinergic nerve endings

ESTERS OF CHOLINE
ACETYLCHOLINE is the prototypical cholinergic agent. It functions as a neurotransmitter at all
cholinergic sites in the body; because of its unique pharmacokinetic properties, it has never
been used in medical therapeutics; the discussion which follows is for academic exercise.
Pharmacokinetics
Acetylcholine is poorly absorbed from the gastric mucosa; therefore it is ineffective if given
orally. The recommended way of administration is parenteral. In the blood it is rapidly
hydrolyzed by the enzyme cholinesterase into acetic acid and choline; this makes its duration of
action very short and unreliable for therapeutic purposes.
Pharmacodynamics
As mentioned earlier it has two types of actions: nicotinic and muscarinic; the muscarinic actions
are of main interest and are discussed below.

Blood vesselsÆ vasodilator
Blood pressureÆ falls because of the effect on the heart and blood revels
i) Gastrointestinal tract
It stimulates the tone and motility of the Gl tract but the sphincters will be relaxed
ii) Urinary tract
It stimulates the detrusor muscle and relaxes the internal urethral sphincter resulting in
evacuation of bladder
iii) Bronchioles
It increase bronchial secretion and brings about bronchoconstriction
iv) Eye- It has two effects- miosis and accommodation for near objects because of stimulation of
the constrictor pupillae and ciliary muscles respectively.
v) Exocrine glands- it stimulates salivary, gastric, bronchial, lachrymal and sweat gland
secretions.
SYNTHETIC CHOLINE ESTERS. These are synthetic derivatives of choline and include
metacholine, carbachol and beta

CARBACHOL

Pharmacokinetics
It is completely absorbed from the gastro intestinal tract and is stable towards hydrolysis by
cholinesterase enzyme; therefore it can be given both orally and parenteraly with almost similar
dosage.
Pharmacodynamics
It has similar actions to those of acetylcholine with pronounced effects on the gastro intestinal
tract and the urinary bladder
Indications

• Glaucoma
• Retention of urine (postoperative)
• Paralytic ileus

BETANECHOL
This drug is similar to carbachol in all parameters, i.e., pharmacokinetics, pharmacodynamics

and clinical indications; it has a better advantage over carbachol because it has fewer side
effects as a result as lack of nicotinic actions.
Contra indications to the use of choline esters

1. Bronchial asthma because they may induce bronchial constriction and increase bronchial
   secretions
2. Hyperthyroidism because of the danger of inducing atrial fibrillation
3. Peptic ulcer disease because of the increase in gastric acid secretion
4. Coronary insufficiency because the hypertension produced will further compromise coronary
   blood flow
5. Mechanical intestinal and urinary outlet obstruction
   CHOLINERGIC ALKALOIDS
6. Those with chiefly nicotinic actions include nicotine, lobeline etc.
7. Those with chiefly muscarinic actions include muscarine, pilocarpine, etc.
   PILOCARPINE
   Pharmacokinetics
   This drug is readily absorbed from the gastrointestinal tract and it is not hydrolyzed by
   cholinesterase enzyme. It is excreted partly destroyed and partly unchanged in the urine.
   Pharmacodynamics
   The drug directly stimulates the muscarinic receptors to bring about all the muscarinic effects of
   acetylcholine.
   Indications

ANTICHOLINESTERASE DRUGS
The commonly used cholinesterase inhibitors fall into three chemical groups:

1. Simple alcohols bearing quaternary amines, e.g., edrophonium
2. Carbamate and related quaternary or tertiary amines, e.g., neostigmine, physostigmine
3. Organic derivatives of phosphates, e.g., isofluorophate, echothiophate

PHYSOSTIGMINE
Pharmacokinetics
This drug is completely absorbed from the gastrointestinal and is highly distributed throughout
the body; it can pass the blood brain barrier.
Pharmacodynamics
Inhibits the enzyme cholinesterase; therefore, it increases and prolongs the effect of
endogenous acetylcholine at the different sites.It has no direct effect on cholinergic receptors.
Indications

• Glaucoma
• Atropine over dosage
  NEOSTIGMINE
  Pharmacokinetics
  This drug is poorly absorbed from the gastro intestinal tract and is poorly distributed throughout
  the body; it cannot pass the blood brain barrier.
  Pharmacodynamics
  Just like physostigmineit inhibits cholinesterase enzyme; but unlike physostigmine, it has a
• direct nicotinic action on skeletal muscles.
• Indications
• Myasthenia gravis
• Paralytic Ileus
• Reversal of effect of muscle relaxants, e.g. tubocurarine
• Post operative urine retention
  Organophosphates such as echothiophate, isofluorophate, etc. combine with cholinesterase
  irreversibly and thus hydrolysis is very slow.
  They may be used in glaucoma. Other organophosphates like parathion and malathion are used
  as insecticides. Poisoning with organophosphates is an important cause of morbidity and
  mortality all over the world. It usually results from:
• Occupational exposure as in persons engaged in spraying insecticides,
• Accidental exposure, and
• Ingestion of any of these compounds with suicidal intent.