Pharmacological actions

Most of these drugs in the category are selective for muscarinic receptors hence produce muscarinic actions. Let’s take their effect on each organ into account.

Heart

On the heart they produce inhibition through M2 receptors

• Decrease in rate of contraction – so they produce bradycardia
• Decrease in force of contraction
• Decrease in AV conduction

Smooth muscle

You can remember easily that all the actions on smooth muscle are mediated through M3 receptors. As M3 receptors are coupled with IP3/DAG system they always produce contraction. But we can find an exception at vascular smooth muscle. So,

Muscarinic agonists can act on M3 reeptors present on vascular endothelium and release nitrc oxide. This released nitric oxide increases cGMP levels in vascular smooth muscle leading to relaxation.

So, now let’s see various smooth muscles and their effect.

Bronchioles

Muscarinic agonists can act on M3 receptors at bronchioles to produce bronchoconstriction. They can also increase bronchial secretions all these may be important in patients with asthma or chronic obstructive pulmonary disorder (COPD).

GI smooth muscle

These drugs can produce GI smooth muscle contraction leading to increase in GI motility. This enhanced motility may result in diarrhea.

But this action can be taken for advantage in the patients with decreased motility. Particularly bethanechol can be used in this condition.

Bladder

These drugs increase the tone of bladder leading to increased frequency of urination. That's why these drugs increase urinary urgency in patients.

Again this action is useful in the patients with bladder hypotonia where bethanechol is prescribed.

Eye

Two important muscles on the eye affected by cholinergic drugs are

• Constrictor muscle
• Ciliary muscle

Constrictor muscle

Constrictor muscle also called as circular muscle, when activated produces pupilary constriction. You can just imagine that if a circle constricts, it's radius also decreases.

Similarly, by constriction of circular muscle, the pupil size decreases. Hence these drugs produce miosis.

Now let's see the effect on second muscle, that is, cilirary muscle. Muscarinic agonists produce contraction of ciliary muscle which leads to bulging of lens. This is required to see the objects at different distances.

The final effect of contraction of these two muscle improve the drainage of aqueous humour from the canal of schlemm. This results in a significant reduction of intraocular pressure which is useful in the treatment of glaucoma.

Pilocarpine is drug specifically used for glaucoma as it produces a significant reduction in intraocular tension

Exocrine glands

Cholinergic agonists increase secretion of exocrine glands by acting on M3 receptors. They produce

• Lacrimal secretion
• Bronchial secretion
• Salivary secretion
• Sweat secretion

Acetylcholine doesn’t produce sweat secretion but muscarinic agonists do. Why?

Nicotinic actions

Only carbachol shows significant affinity for nicotinic receptors and all the actions are unwanted.

It can increase stimulation of ganglia initially followed by inhibition. It can also increase the release of adrenaline from adrenal medulla increasing blood pressure.

But all these are practically not observed as carbachol has little therapeutic use today.