グアネチジン

Very soluble

WHITE, CRYSTALLINE POWDER; STRONG CHARACTERISTIC ODOR; SPARINGLY SOL IN WATER; SLIGHTLY SOL IN ALC; PRACTICALLY INSOL IN CHLOROFORM /SULFATE/

WHITE, CRYSTALLINE POWDER; VERY SOL IN H2O; INSOL IN NONPOLAR SOLVENTS /MONOSULFATE/

2.25e+00 g/L

276-281

250 °C (sulfate salt)

MONOAMINE OXIDASE INHIBITORS HAVE BEEN REPORTED TO ANTAGONIZE ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE.

TOPICALLY ADMIN GUANETHIDINE ENHANCES RESPONSE OF EYE TO TOPICALLY ADMIN PHENYLEPHRINE, RESULTING IN INCR MYDRIASIS.

THIAZIDES ENHANCE ANTIHYPERTENSIVE ACTION OF GUANETHIDINE, ALLOWING DOSE OF GUANETHIDINE TO BE REDUCED & DECR INCIDENCE OF ADVERSE REACTIONS...

ANTIHYPERTENSIVE ACTION OF GUANETHIDINE MAY BE BLOCKED BY DEXTROAMPHETAMINE & RELATED COMPD; THEREFORE, CONCURRENT USE OF THESE DRUGS SHOULD BE AVOIDED.

For more Interactions (Complete) data for GUANETHIDINE (10 total), please visit the HSDB record page.

SOME TENDENCY TO DIARRHEA IS ASSOC WITH GUANETHIDINE THERAPY IN HIGH PERCENTAGE OF CASES... INHIBITION OF EJACULATION IS COMMON, & IMPOTENCE MAY BE PSCHOGENIC AFTERMATH. ...CAN CAUSE SEVERE HYPERTENSIVE REACTIONS IN PT WITH PHEOCHROMOCYTOMA.

HYPOTENSIVE EPISODES MAY BE ASSOC WITH SYMPTOMS OF CEREBRAL & MYOCARDIAL ISCHEMIA. ... GENERALIZED SUBJECTIVE "WEAKNESS" IS COMMON... FLUID RETENTION OCCURS & CAN LEAD TO EDEMA & RESISTANCE TO ANTIHYPERTENSIVE EFFECT IF DIURETIC IS NOT GIVEN CONCURRENTLY. ...CAN LEAD TO...HEART FAILURE IN PT WITH LIMITED CARDIAC RESERVE.

MOST IMPORTANT COMPLICATION OF GUANETHIDINE THERAPY IS POSTURAL HYPOTENSION; IT IS MOST PROMINENT SHORTLY AFTER ARISING FROM SLEEP & MAY BE ACCENTUATED BY HOT WEATHER, ALCOHOL, OR EXERCISE.

APPLICATION OF 5%-10% GUANETHIDINE SULFATE SOLN TO EYES OF PT HAS INDUCED SLIGHT MIOSIS, NOTICEABLE PTOSIS & HYPEREMIA FROM ANTIADRENERGIC ACTION. ... 50% OF PT WITH THYROID DYSFUNCTION & EXOPHTHALMOS HAVE DEVELOPED SUPERFICIAL CHANGES IN CORNEAL EPITHELIUM AFTER 1-8 WK OF APPLYING SOLN TWICE DAY. /SULFATE/

For more Human Toxicity Excerpts (Complete) data for GUANETHIDINE (9 total), please visit the HSDB record page.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

guanethidine

Ismelin®

Antiadrenergics

Not Applicable

no-DILI-concern

S - Sensory organs

C - Cardiovascular system

QS - Sensory organs

QC - Cardiovascular system

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.

Guanethidine acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine (NE), rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters to be concentrated within the transmitter vesicles in place of NE, leading to gradual depletion of NE stores in the nerve endings. Guanethidine at the nerve terminal blocks the release of noradrenaline in response to 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.

GUANETHIDINE MAY BE CONSIDERED REPRESENTATIVE OF DRUGS THAT DEPRESS FUNCTION OF POSTGANGLIONIC ADRENERGIC NERVES.

RAPID IV INJECTION...PRODUCES...INITIAL RAPID FALL IN BLOOD PRESSURE ASSOC WITH INCR CARDIAC OUTPUT & DECR PERIPHERAL RESISTANCE; LATTER IS PROBABLY DUE TO TRANSIENT DIRECT ACTION OF DRUG ON RESISTANCE VESSELS. FALL IN BLOOD PRESSURE IS FOLLOWED BY HYPERTENSION...

MAJOR EFFECT...INHIBITION OF RESPONSES TO SYMPATHETIC ADRENERGIC NERVE ACTIVATION & TO INDIRECT-ACTING SYMPATHOMIMETIC AMINES. SINCE GUANETHIDINE ALSO SENSITIZES EFFECTOR CELLS TO CATECHOLAMINES, EFFECTIVE BLOCK MUST MEAN THAT AMT OF MEDIATOR RELEASED IS DRASTICALLY REDUCED. ...HAS CONSIDERABLE LOCAL ANESTHETIC ACTIVITY...

GUANETHIDINE APPARENTLY ACCUMULATES IN & DISPLACES NOREPINEPHRINE FROM INTRANEURONAL STORAGE GRANULES, & IS ITSELF RELEASED BY NERVE STIMULATION. THUS IT FITS DEFINITION OF "FALSE TRANSMITTER" BUT THIS MECHANISM APPEARS NOT TO BE RESPONSIBLE FOR ITS EFFECTS.

For more Mechanism of Action (Complete) data for GUANETHIDINE (7 total), please visit the HSDB record page.

1.5 days

...GUANETHIDINE...IS BOUND TO PLASMA PROTEINS & TISSUES, CAUSING PROLONGED T/2 OF ABOUT 30 HR.

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.

METABOLISM APPEARS TO BE BY HEPATIC MICROSOMAL ENZYMES, & PERCENTAGE METABOLIZED IS CONSIDERABLY HIGHER AFTER ORAL THAN AFTER PARENTERAL ADMIN.

...TERTIARY NITROGEN OF PERHYDROAZOCINE RING UNDERGOES N-OXIDATION TO SIGNIFICANT EXTENT IN MAN.

HYPOTENSIVE PT ON GUANETHIDINE ELIMINATED VIA KIDNEYS UNCHANGED, ALSO GUANETHIDINE N-OXIDE, & 2-(6-CARBOXYHEXYLAMINO)-ETHYLGUANIDINE.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the ADRENERGIC ANTAGONISTS and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals (see ADRENERGIC AGENTS). Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists, see ADRENERGIC ALPHA-AGONISTS) are included here.

Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.

3-30% of oral dose (poor and highly variable)

Ismelin is converted by the liver to three metabolites, which are excreted in the urine.

Renal cl=56 ml/min

...30 MIN AFTER IP ADMIN OF [(14)C]-GUANETHIDINE, ANTIHYPERTENSIVE AGENT, TO MICE, MOST OF [(14)C] WAS DISTRIBUTED IN LIVER, GI TRACT, SPLEEN, KIDNEYS, URINARY BLADDER, SALIVARY GLANDS, & BROWN FAT. IN RAT, LEVELS...IN PLASMA WERE LOWER THAN IN TISSUES...1-2 HR AFTER IP ADMIN.

HUMAN SUBJECTS RECEIVING GUANETHIDINE, HAD EXCRETED 24% OF [(14)C] IN URINE 24 HR AFTER ORAL DOSE, & 52% AFTER IV DOSE. EXCRETION OF (14)C CONTINUED, & ABOUT HALF AMT EXCRETED IN 24 HR WAS PRESENT IN URINE AFTER FURTHER 48 HR. IN 72 HR ABOUT 23% WAS EXCRETED IN FECES AFTER ORAL DOSE & 3% AFTER IV DOSE.

MUCH OF IV DOSE OF [(3)H]GUANETHIDINE WAS EXCRETED UNCHANGED IN URINE OF HUMAN HYPERTENSIVE SUBJECTS; MORE SLOWLY FROM THOSE SUFFERING ADDITIONALLY FROM RENAL FAILURE.

GUANETHIDINE SULFATE, USP (ISMELIN), IS AVAILABLE IN 10- & 25-MG TABLETS FOR ORAL ADMIN. /SULFATE/

...MARKETED ONLY IN 10:25 COMBINATION WITH HYDROCHLOROTHIAZIDE. /MONOSULFATE/