Acetyicholine is the neurotransmitter in both sympathetic and parasympathetic ganglia. Transmission through autonomic Ganglionic is complex. Both types of cholinergic receptors are present at postganglionic neurone cell bodies. Acetylcholine, released from preganglionic fibres, produces a series of changes as follows:
The primary event is that acetyicholine acts on postsynaptic nicotinic (N1) receptor and causes depolarization and propagation of excitatory postsynaptic potential (EPSP). Acetylcholine also releases noradrenaline and dopamine from interneurons which generate inhibitory postsynaptic potential (IPSP). Finally there develops late excitatory postsynaptic potential (late EPSP) due to release of number of cotransmitters such as peptides (neuropeptide Y, VIP, LHRH, angiotensin-Il, enkephaline and substance P), amines (histamine, 5HT) and GABA. This is followed by hydrolysis of acetylcholine by cholinesterase and repolarization.
They are not used in therapeutics. But they are of considerable importance because of nicotine which has the ability to stimulate (in small doses)as well as block (in large doses) ganglionic receptors. The other ganglionic stimulants are lobeline,tetramethylamrrtonium and 1, 1-dimethyl 1-4-phenyl piperazinium (DMPP).
Nicotine: It is an alkaloid obtained from the leaves of tobacco plant (Nicotiana tobacum). It is a brown liquid. It can easily penetrate intact skin and mucous membranes. On inhalation of nicotine, cigarette smoke (0.3 to I mg) may cause slight increase in heart rate, blood pressure and respiration. Skin temperature may decrease. Nicotine or Ganglionic blockers may cause tremors, convulsions, nausea, vomiting and release of antidiuretic hormone from pituitary.
Nicotine or ganglionic blockers increases the gastric, salivary and bronchial secretions. Nicotine smoking causes an induction of metabolizing enzymes in the liver and intestine. Nicotine produces tolerance to its central effects rapidly. It also produces dependence and symptoms of withdrawal may appear within 24 hours. Clonidine has been found to be effective to reduce craving and insomnia.
Adverse reactions: Smoking is injurious to health. Chronic smoking may lead to:
- Dyspnoea, wheezing, pain chest, and upper respiratory tract infection
- Increased incidence of cancer of oral, laryngeal, oesophageal, duodenal, pancreatic lung and bladder
- Increased incidence of hypertension, ischaemic heart disease and thromboangitis obliterance
- Anxiety, insomnia, irritability and depression
- Increased incidence of pre-eclampsia, abortion, low birth weight and fewer pregnancies
- Toxic amblyopia may occur in smokers of strong tobacco and cheap cigarettes.
Ganglionic Blocking Agents
These drugs block the transmission across the autonomic ganglia. Once they were extensively used in the treatment of hypertension. However, now they have limited use because of the following reasons:
- High incidence of undesirable side effects due to their non-specific nature of action, i.e. they block both sympathetic and parasympathetic autonomic ganglia.
- Development of tolerance to hypotensive effect rapidly.
- Unpredictable absorption from the gut.
- Advent of safer and equally potent hypotensive agents.
- The ones which are still in use are mecamylamine and trimethaphan.
Mecamylamine: It is a secondary amine. On oral administration, it is almost completely absorbed and can also cross the blood—brain barrier. So it produces prominent central nervous system effects such as tremor, confusion, seizures, mania and depression. It is excreted unchanged by the kidney. On prolonged use, mecamylamine produces tolerance. The common adverse effects are postural hypotension (due to blockade of normal protective vasomotor reflexes mediated through baroreceptors and the sympathetic nervous system), drowsiness, dry mouth, impotence, paralytic ileus. Dose: Initial 2.5 mg twice daily; gradually increased up to 20—30 mg per day. It is used in the treatment of moderate to severe hypertension if other drugs are ineffective.
Trimethaphan (arfonad): It has a very short duration of action. It is only used as intravenous infusion (3—4 mg/mm) to produce controlled hypotension in surgery. It should be carefully used in patients of allergy because it releases histamine.
Points for Dental Students
It is important to know whether a patient is a smoker or not because nicotine smoking causes an induction of metabolizing enzymes in the liver and intestine. It means the metabolism of number of drugs such as betaadrenoceptor blocking agents, corticoids, calcium channel blockers, doxycycline, estrogens, itraconazole, ketoconazole, phenothiazines, quinidine, etc. is increased. So dosage adjustment is needed when one of these drugs is used clinically to have a desired therapeutic effect.
I. Acetylcholine is the neurotransmitter in both sympathetic and parasympathetic ganglia.
2. Ganglionic stimulants are not used in therapeutics but they are of considerable importance because of nicotine abuse. Nicotine produces tolerance, and dependence and withdrawal may appear within 24 hours. Clonidine has been found to be effective to reduce craving and insomnia.
3. Ganglionic blocking agents block the transmission across the autonomic ganglia. Ganglionic agents have limited use in hypertension because of high incidence of undesirable side effects, development of tolerance to hypotensive effect and unpredictable absorption from gut.
4. Mecamylamine is a secondary amine which is used in moderate to severe hypertension if other drugs are ineffective.
5. Trimetaphan (arfonad) is an ultrashort acting ganglionic blocking agent which is used to produce controlled hypotension in neurosurgery.