| Indication |
For the treatment of moderate and severe hypertension, either
alone or as an adjunct, and for the treatment of renal hypertension. |
| Pharmacodynamics |
High blood pressure can cause the heart and arteries to not
function properly. This can damage the blood vessels of the brain,
heart, and kidneys, resulting in a stroke, heart failure, or kidney
failure. High blood pressure may also increase the risk of heart
attacks. These problems may be less likely to occur if blood pressure is
controlled. Guanethidine works by decreasing the heart rate and
relaxing the blood vessels so that blood can flow more easily through
the body, thereby reducing these risks. It is a postganglionic
sympathetic nerve terminal blocker that prevents the release of
norepinephrine from nerve terminals. |
| Mechanism of action |
Guanethidine acts at the sympathetic neuroeffector junction by
inhibiting or interfering with the release and/or distribution of
norepinephrine, rather than acting at the effector cell by inhibiting
the association of norepinephrine with its receptors. It is taken up by
norepinephrine transporters. It becomes concentrated in NE transmitter
vesicles, replacing NE in these vesicles. This leads to a gradual
depletion of NE stores in the nerve endings. Once inside the terminal it
blocks the release of noradrenaline in response to arrival of an action
potential. In contrast to ganglionic blocking agents, Guanethidine
suppresses equally the responses mediated by alpha-and beta-adrenergic
receptors but does not produce parasympathetic blockade. Since
sympathetic blockade results in modest decreases in peripheral
resistance and cardiac output, Guanethidine lowers blood pressure in the
supine position. It further reduces blood pressure by decreasing the
degree of vasoconstriction that normally results from reflex sympathetic
nervous activity upon assumption of the upright posture, thus reducing
venous return and cardiac output more. |
| Absorption |
3-30% of oral dose (poor and highly variable) |
| Volume of distribution |
Not Available |
| Protein binding |
Not Available |
| Metabolism |
Guanethidine is converted by the liver to three metabolites,
which are excreted in the urine. The metabolites are pharmacologically
less active than the parent compound. |
| Route of elimination |
Ismelin is converted by the liver to three metabolites, which are excreted in the urine. |
| Half life |
1.5 days |
| Clearance |
|
| Toxicity |
Side effects include drowsiness, dizziness, tiredness or confusion. LD50=1000 mg/kg (mouse, oral) |
