Guanethidine

198.30848

198.31

200-241-3

ZTI6C33Q2Q

DTXSID5023116

C - Cardiovascular system|S - Sensory organs

67.6

0.8

Solid

1.13g/cm3

250 °C (sulfate salt)

345.6ºC at 760mmHg

162.8ºC

1.4910 (estimate)

H2O: Very soluble

LD50 oral in rat: 1050mg/kg

CRYSTALS FROM DIL ETHANOL; MP 276-281 °C (DECOMP) /SULFATE/

Side effects include drowsiness, dizziness, tiredness or confusion. LD50=1000 mg/kg (mouse, oral)

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.

For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.

Adrenergic Agents; Antihypertensive Agents; Sympatholytics|ONLY MAJOR USE OF GUANETHIDINE IS IN TREATMENT OF HYPERTENSION... IT ALSO EFFECTIVELY CONTROLS PRESSOR EPISODES ASSOC WITH HYPERREFLEXIA OF HIGH SPINAL CORD LESIONS. LOCAL APPLICATION OF GUANETHIDINE HAS RECEIVED LIMITED TRIAL IN TREATMENT OF GLAUCOMA...& TO PRODUCE PARTIAL HORNER'S SYNDROME IN...ABNORMAL EYELID RETRACTION.|GUANETHIDINE...MAY BE USEFUL ADJUNCTS TO ANTITHYROID AGENTS IN HYPERTHYROIDISM & THYROTOXIC CRISIS.|GUANETHIDINE...HAS BEEN USED...IN EYEDROPS FOR REDUCING INTRAOCULAR PRESSURE IN GLAUCOMA & FOR REDUCING LID RETRACTION IN THYROID DISEASE.|For more Therapeutic Uses (Complete) data for GUANETHIDINE (6 total), please visit the HSDB record page.

GUANETHIDINE INHIBITS CARDIOVASCULAR REFLEXES...INCR GASTROINTESTINAL MOTILITY... SALT & WATER RETENTION...CAN PROBABLY BE ACCOUNTED FOR BY HEMODYNAMIC EFFECTS...|SENSITIZATION BY GUANETHIDINE TO SOME SYMPATHOMIMETICS FOUND IN "COLD REMEDIES" CAN RESULT IN HYPERTENSIVE CRISES.

TOLERANCE IS RARE & IS OF LOW DEGREE. /SULFATE/

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.

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. (See all compounds classified as Sympatholytics.)|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. (See all compounds classified as Adrenergic Agents.)|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. (See all compounds classified as Antihypertensive Agents.)

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.|...PENETRATES CNS VERY POORLY AFTER SYSTEMIC ADMIN. ... GUANETHIDINE IS TAKEN UP BY & STORED IN ADRENERGIC NERVES, & THIS ACCUMULATION IS ESSENTIAL FOR ITS ACTION.|For more Absorption, Distribution and Excretion (Complete) data for GUANETHIDINE (6 total), please visit the HSDB record page.

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.

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

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.

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.

((2-Hexahydro-1(2H)-azocinyl)ethyl)guanidine

GUANETHIDINE SULFATE, USP (ISMELIN), IS AVAILABLE IN 10- & 25-MG TABLETS FOR ORAL ADMIN. /SULFATE/|...MARKETED ONLY IN 10:25 COMBINATION WITH HYDROCHLOROTHIAZIDE. /MONOSULFATE/

GAS CHROMATOGRAPHIC DETERMINATION OF GUANETHIDINE IN BIOLOGICAL FLUIDS.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals