Drugs Acting On Autonomic Ganglia

Drugs acting on autonomic ganglia act on both sympathetic and parasympathetic ganglia without specificity and either (stimulate or inhibit discharges from post ganglionic fibers). These are classified into Autonomic ganglionic stimulating drugs and Autonomic ganglionic blocking drugs.

• Autonomic ganglionic stimulating drugs are further divided into
  1. Natural alkaloids– Nicotine, Lobeline
  2. Synthetic drugs– Tetramethyl ammonium (TMA), Dimethyl Phenyl Piperazinium (DMPP)

• Autonomic ganglionic blocking drugs are subdivided into
  1.  Persisting depolarizing ganglionic blocking drugs– Nicotine (large doses)
  2. Non-depolarizing ganglionic blocking drugs– Hexamethonium, Pentalinium, Pentamethonium, Mecamylamine, pempidine, Trimethaphan

Ganglionic stimulants

Ganglionic stimulants do not find much clinical uses. Nicotine is available as transdermal patches for the treatment of nicotine dependence and as an aid to smoking cessation. Side effects of these patches include: headache, insomnia, flu like symptoms, dyspepsia, loose motion and local irritation.

• Ganglionic stimulants can be classified as
  1. Selective nicotinic agonists include: Nicotine in small doses, lobeline, dimethyl phenyl piperazinum iodide, tetramethyl ammonium.
  2. Non-selective/muscarinic agonists include: Acetylcholine, carbachol, pilocarpine and anticholinesterases.

Pharmacological actions of ganglionic stimulants

1. Central nervous system
   • Nicotine is an extremely toxic substance that transiently stimulates and then depresses the CNS.
   • Death is from respiratory paralysis of the diaphragm and chest muscles resulting from descending paralysis.
   • Nicotine is absorbed through the chitinous shell of insects after a direct spraying or after contacting a sprayed surface and kills the insect by paralysis.
2. Cardiovascular system
   • Small doses of nicotine activate both caridoaccelerator and cardioinhibitory nerves. Since cardioinhibitory nerve is more predominant, decreased pulse rate is noticed.
   • Due to paralysis of the autonomic ganglia after a large dose of nicotine, the heart rate returns towards normal.
   • Small doses of nicotine can cause a pressor response due to the sympathetic stimulation.
   • Peripheral vasodilatation results after a large dose due to autonomic ganglionic blockade.
3. Gastrointestinal system
   • Activates both the smooth muscles and secretory glands of the digestive tract and produce excessive salivation, increased gastric secretion, vomiting, increased peristalsis and defecation.
4. Skeletal muscle
   • Initially stimulates nicotinic receptors of the motor end plate and in large doses produces a depolarising muscle paralysis.
5. Acute nicotine poisoning
   • Excitement, hyperapnea, salivation, pulse rate irregularities, diarrhoea and emesis. After this transient stimulatory phase, a depressed state characterised by incoordination, tachycardia, dyspnoea, coma and death from respiratory paralysis.

Ganglionic blockers

Small doses of nicotine can stimulate autonomic ganglion cells and large doses can block the transmitter functions of acetylcholine at the same sites. Though it was originally believed that ganglionic neurons have only nicotinic receptors, it has now been demonstrated that secondary excitatory pathway that is apparently muscarinic and inhibitory catecholaminergic mechanisms have also been demonstrated. But the drugs that exert significant autonomic ganglionic blocking effect do so, by blocking the nicotinic receptors.

Pharmacological actions of ganglionic blockers

Organ	Predominant tone	Effects of ganglionic blockade
Cardiovascular	–	Overall depression
Arterioles	Sympathetic	Vasodilatation, increased peripheral blood flow, hypotension
Veins	Sympathetic	Vasodilatation, pooling of blood, decreased venous return
Heart	Parasympathetic	Tachycardia
Gastrointestinal tract	Parasympathetic	Decreased tone and motility, constipation
Eye	–	–
Iris	Parasympathetic	Mydriasis
Ciliary muscle	Parasympathetic	Cycloplegia
Urinary bladder	Parasympathetic	Urinary retention
Salivary glands	Parasympathetic	Dry mouth
Sweat glands	Sympathetic	Anhydrosis
Bronchioles	Parasympathetic	Relaxation, decreased secretion

Autonomic Pharmacology of the Eye

The sphincter muscles (constrictor pupillae) are innervated by the parasympathetic system. Stimulation of these muscles results in contraction of the muscle and in turn pupillary constriction (miosis).

Radial muscles are innervated by the sympathetic system. Stimulation of these muscles results in contraction of dilator muscles and in turn pupillary dilatation (mydriasis). However, the activity of parasympathetic system predominates.

The ciliary muscles receive modest sympathetic innervation. Parasympathetic activity of ciliary muscle leads to contraction of the ciliary muscle, relaxation of the ligaments to the lens and the lens becomes more globular with accommodation to near vision.

Atropine

Atropine has a very long duration of action on the iris. it causes relaxation of the iris sphincter muscle pupillary dilatation. Atropine causes relaxation of the ciliary muscle and paralysis of accommodation (cycloplegia). This effect is also long lasting.

Pilocarpine

Pilocarpine causes contraction of the iris sphincter and miosis. and can counter the mydriasis caused by atropine.

On the cilicary muscle pilocarpine and cholinesterase inhibitors cause contraction and in turn accommodation to near vision. Shorter acting muscarinic antagonists like tropicamide have been developed for use in ophthalmology. Ganglionic blockade also causes cycloplegia.

Glaucoma 

In glaucoma parasympathomimetic and anticholinesterase drugs produce a fall in intraocular pressure mainly by lowering the resistance to outflow of aqueous humor. In narrow angle glaucoma, which is acute congestive, drugs are used to reduce pressure at the time of attack and until surgery (iridectomy).

The outflow of aqueous humor is facilitated, by freeing the entrance to the trabecular space at the canal of Schlemm from blockade by iris tissue. This is accomplished by inducing miosis and contraction of the ciliary muscle. Drugs useful in narrow angle glaucoma include parasympathomimetic drugs like physostigmine and pilocarpine, carbonic anhydrase inhibitors like acetazolamide (they inhibit the formation of aqueous humor) and osmotic diuretics like mannitol and glycerine (they produce intraocular dehydration).

Atropine either applied locally for ophthalmology or given parenterally prior to anaesthesia and other sympathomimetics and antihistaminics are contraindicated in narrow angle glaucoma as they can precipitate an attack of acute congestive glaucoma. In wide angle glaucoma, which is chronic and simple surgical correction is not possible. Long term correction with drugs like pilocarpine, physostigmine or carbachol is necessary.

Diisopropylfluorophosphate or echothiophate can be used to treat glaucoma. Their major advantage is frequent ocular administration is not required. Other drugs used include timolol, epinephrine, phenylephrine, prazosin and acetazolamide are also useful in wide angle glaucoma.