Guanethidine is an antihypertensive

Antihypertensive

The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 drug that reduces the release of catecholamines, such as norepinephrine

Norepinephrine

Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself (NET, uptake 1), and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine.

Side effects

Side effects include orthostatic and exercise hypotension

Hypotension

In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...

, sexual dysfunction

Sexual dysfunction

Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....

 (delayed or retrograde ejaculation

Retrograde ejaculation

In the human male reproductive system, retrograde ejaculation occurs when semen, which would normally be ejaculated via the urethra, is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation forcing the semen to exit via the urethra, the path of least...

), and diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

.

Pharmacology

Guanethidine is transported by uptake 1 into the presynaptic terminal transported by Norepinephrine transporter (NET). (In this it competes with norepinephrine so can potentiate exogenously applied norepinephrine). It becomes concentrated in norepinephrine transmitter vesicles, replacing norepinephrine in these vesicles. This leads to a gradual depletion of norepinephrine stores in the nerve endings.
Once inside the terminal it blocks the release of norepinephrine in response to arrival of an action potential. Spontaneous release is not affected.

Uses

Guanethidine was once a mainstay for hypertension resistant to other agents, and was often used safely during pregnancy, but it is no longer used in the US due to lack of availability. It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a hypertensive emergency

Hypertensive emergency

Malignant hypertension or hypertensive emergency is severe hypertension with acute impairment of an organ system and the possibility of irreversible organ-damage...

.

Intravenous nerve block (Bier block

Intravenous regional anesthesia

Intravenous regional anesthesia or Bier block anesthesia is a common anesthetic technique for surgical procedures on the body's extremities where a local anesthetic is injected intravenously. The technique usually involves exsanguination, which forces blood out of the extremity, followed by the...

) using guanethidine has been used to treat chronic pain

Chronic pain

Chronic pain has several different meanings in medicine. Traditionally, the distinction between acute and chronic pain has relied upon an arbitrary interval of time from onset; the two most commonly used markers being 3 months and 6 months since the initiation of pain, though some theorists and...

 caused by complex regional pain syndrome

Complex regional pain syndrome

Complex regional pain syndrome is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. It often affects an arm or a leg and may spread to another part of the body.Though treatment is often unsatisfactory, early multimodal therapy can cause dramatic...

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Chemistry

Th starting material for synthetizing guanethidine, Azocine

Azocine

Azocine is a heterocyclic organic compound with the molecular formula C7H7N. It consists of an unsaturated eight-membered ring having seven carbon atoms, one nitrogen atom and four double bonds....

 is alkylated by chloroacetonitrile. This reaction which forms 1-azocinylacetonitrile, which can be reduced into 1-(2-aminoethyl)azocine by using lithium aluminum hydride as a reductant. This compound reacts with S-methylthiourea forming guanethidine.

• R.P. Mull, (1960).
• R.P. Mull, (1961).
• R.P. Mull, (1962).