2. Drugs acting on Autonomic nervous system

Adrenergic Neuron Blockers and Guanethidine

Once impulse arrives, calcium moves in, resulting in excitation-secretion coupling. To save dopamine, it is taken up by storage vesicles because monoamine oxidase metabolizes any neurotransmitter present.

Drugs may:

  1. Interfere with synthesis of noradrenaline (Methyrosine)
  2. Interfere with storage of dopamine (Reserpine)
  3. Interfere with release of noradrenaline (Guanethidine)
Drugs which prevent release of noradrenaline
  • Guanethidine
  • Guanadrel
  • Bethanidine
  • Debrisoquine
  • Bretylium

Drugs that inhibit storage of noradrenaline

  • Reserpine

Drugs that interfere with synthesis of noradrenaline:



Source and structure:

Synthetic drug, polar, thus it is difficult for it to cross the blood brain barrier. Has peripheral action, and not central. Half life is 5 days.

Mechanism of action

1. Reuptake 1 or uptake 1

This is necessary for the action to occur. After it is reuptaken, it blocks the release of noradrenaline.

2. Membrane stabilizing effect (MSA)

Guanethidine has local anaesthetic effect. It decreases the movement of ions across membrane, thus decreasing the action potential and NE release. It decreases the excitation-secretion coupling.

3. Displacement of noradrenaline

4. Substitute neurotransmitter

Once guanethidine displaces noradrenaline, it is located in the storage vesicles. Every time action potential arrives; guanethidine is released, which is devoid of activity on alpha and beta receptors. Thus acts as a false neurotransmitter.

5. Blocks sympathetic system


Very high volume of distribution, as drug is present within storage vesicles. Oral bioavailability is low i.e. 5-50%. Steady state concentration is achieved after 20 days. Any dose cannot be adjusted before this time. Sympathoplegia persists even after cessation of therapy for some time.

When taken orally, only fall in blood pressure occurs.

Half life is about 5 days.

Pharmacological effects


Causes decrease in blood pressure and decreased TPR as well as cardiac output. Sympathoplegia results in bradycardia, dilatation of capacitance venules occurs, thus pooling of blood takes place decreasing the venous return. This causes decreased cardiac output. TPR also decreases sympathoplegia.

Actions depend on the route of administration and how rapidly given:

1. If rapidly given I/V triphasic response of blood pressure is observed. Initial fall is followed by rise, which is followed by gradual fall:

Initial fall is due to the ability of drug to block noradrenaline. Once taken up, more drug reaches the cytoplasm and displaces noradrenaline. Overwhelming quantity of noradrenaline is displaced, some of which spills out of the nerve terminal and reaches the systemic circulation. This is responsible for the rise. After some time all neurotransmitter is displaced, and guanethidine behaves as a false neurotransmitter, then a decline is observed.

2. If given slowly I/V, only biphasic response is seen. There is no initial fall.

The drug is taken up by the storage vesicles, noradrenaline is released, thus rise is observed on slow I/V injection, once false neurotransmitter acts, fall is seen.

3. If drug is given orally, levels rise slowly, only monophasic response occurs.

Local anaesthetic activity occurs, and as substitute offsets the release of noradrenaline, MAO takes care of the noradrenaline released.

Increased sympathetic activity is associated with increased guanethidine activity.


Initially slightly decrease in blood flow occurs because of auto regulation. Later salt and water retention causes increase in plasma volume and increased blood pressure, thus pseudo tolerance is seen. Diuretics may be given as remedy.


Blocks sympathetic activity, increasing the parasympathetic activity, which leads to increased motility of gut. This might result in abdominal cramps, diarrhoea.


Dilator pupillae are blocked, parasympathetic sphincter has unopposed action causing miosis. Decrease in intraocular pressure is also observed.


Drug does not cross BBB, so has no effect.

Therapeutic uses


This was mainly used quite some time back, now its usage is obsolete. Better options are available having less toxicity. Also this drug blocks sympathetic system, thus super sensitivity occurs at catecholamine receptors.

Adverse effects

1. Postural Hypotension (under control baroreceptors, increased sympathetic discharge blocked so only acting peripherally)
2.  Weakness
3. Worsening of CCF (heart is not pumping enough, no Frank Starlings’ law and no increase in sympathetic activity.)
4. Fluid Retention(long term control HTN by kidneys. When blood pressure is decreased:

a. Redistribution of intra-renal blood flow occurs, independent of renin secretion, leading to salt and water retention.

b. Because of rennin secretion, stimulation of rennin-angiotensin-aldosterone axis occurs, leading to salt and water retention.

Antihypertensive effects are blunted by this fluid retention and tolerance develops. Thus these drugs work best when combined with diuretic.

5. Diarrhoea (over activity of parasympathetic system)
6. Delayed Ejaculation (retrograde ejaculation as sympathetic system is blocked)
7. Nasal Congestion (depending upon blood flow, increase in no. and decrease in size. Also increased blood flow because of sympathoplegia, there is increased size of turbinates in lateral wall leading to nasal congestion)

Drug Interactions:

If drug is not reuptaken, no effect is produced. TAD, cocaine and Phenylpropanolamine (nasal decongestant) completely block the actions. Thus they cannot be given together.

Guanethidine may cause super sensitivity of receptors, leading to up regulation of alpha 1 receptors causing intense vasoconstriction (HTN crisis).  

M.A.O- Reuptake 1Blockage Mg++ ATP pump
Pharmacological Actions- tiphasic, biphasic, monophasic response Gradual fall in blood pressure
Postural hypotensionNo or mild postural hypotension
Therapeutic Uses
No suicidal tendenciesSuicidal tendencies

Continue Reading




Source and chemistry:

Natural alkaloid obtained from root of plant “rauwolfia serpentina” (snake root) which is abundant in the subcontinent (“chandan booti”)

Non polar, so can cross BBB rapidly. Central and peripheral action occurs (unlike guanethidine).

Mechanism of action:

  1. Acting on Mg++- ATP pump, blocks it irreversibly (which is required for uptake of biogenic amines from cytoplasm into storage vesicles), thus depletion and decreased uptake of biogenic amines occurs in both central and peripheral neurons. As a result degradation of biogenic amines occurs.
  2. Serotonin decreased
  3. Conversion of dopamine into NE cannot take place, so synthesis of VMAT s required.

The drug crosses blood brain barrier.

Pharmacological actions:


Decreases blood pressure. The fall is gradual as the drug blocks storage pumps both centrally and peripherally acting drug. Surprisingly no or mild postural hypotension is seen. This is because centrally acting drugs do not produce postural hypotension. Baroreceptor sensitivity is increased even further (some spare baroreceptors).


Decrease in dopamine produces antipsychotic effects

Decrease in NE produces antihypertensive effects

Decrease in serotonin produces antiemetic effects.

Therapeutic uses

1. Hypertension (0.25 mg/day very low dose)
2. Antipsychotic

Two entities affect CNS, depression on one hand and psychosis on other. Depression is because of decrease in biogenic amines while psychosis is always due to increase in number of biogenic amines (amphetamines). All drugs or conditions decreasing the levels produce depression. Reserpine depletes the stores of these biogenic amines, and was used in older days as antipsychotic.

3. Anti emetic

Adverse effects:


  1. sedation
  2. depression (producing suicidal tendencies, one reason why use discontinued)
  3. extra pyramidal effects decreasing the levels of biogenic amines in nigrostriatal pathway (due to decrease in dopamine, parkinsonism like symptoms)
  4.  nightmares


(block sympathetic system peripherally) 

  1. Diarrhoea
  2. Acidity (contraindicated in ulcers)

Nasal stuffiness

(due to increased blood flow)

Reproductive system

Decrease in libido

 Drug interactions

Interferes with action of drugs used in Parkinsonism like levo dopa.


Peptic ulcer


M.A.O- Reuptake 1Blockage Mg++ ATP pump
Pharmacological Actions- tiphasic, biphasic, monophasic response Gradual fall in blood pressure
Postural hypotensionNo or mild postural hypotension
Therapeutic Uses
No suicidal tendenciesSuicidal tendencies


Bretylium is an adrenergic neuron blocker used as antiarrhythmic drug (class III). It prolongs the duration of ventricular action potential, thus used in treatment of ventricular fibrillation.

The effective refractory period of ischemic heart tissue is shortened which becomes more excitable, leading to rhythm disturbance. This drug is more effective in ischemic tissue as it prolongs the refractory period and is used in conditions where lignocaine and defibrillation have failed.

Mechanism of Action:

a. Has MSA (decreases release of NE)

b. Blocks K+ channels increasing duration of action potential and refractory period (blocks re-entry circuits)


Given by oral route and having a half life of about 9 hours.


  1. Anti-arrhythmic
  2. Antihypertensive

Adverse effects:

Postural hypotension



Treatment of Ventricular Fibrillation:

  1. Electrical defibrillation
  2. Lignocaine
  3. Bretylium
  4. Amidorone

Leave a Reply

Your email address will not be published. Required fields are marked *