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Clonidine metabolism

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  1. KA6AH_KA3AHOCTPA Well-Known Member

    Clonidine metabolism


    PO administration: 0.1-0.3 mg q4-6hr; increase by 0.1 mg/day to 0.15-0.75 mg/day if required; do not exceed 2.4 mg/day TD administration: 100-200 mcg/day patch q7Days; initiate 0.1-0.3 mg PO q4-6hr for first 2 days to allow for adequate drug levels Not recommended as routine treatment for hypertension (Beers criteria) Potential for orthostatic hypotension and adverse CNS effects May cause bradycardia Immediate release: Lower initial doses than for nongeriatric adult dosing, as well as gradual adjustments, are recommended Extended release: May require lower initial dose than for nongeriatric adult dosing Skin reactions; patch (15-50%) Dry mouth (40%) Somnolence (19-38%) Headache (19-29%) Fatigue (13-24%) Drowsiness (33%) Dizziness (13-16%) Hypotension, epidural (45%) Postural hypotension, epidural (32%) Anxiety (11%) Epidural clonidine is not recommended for obstetric postpartum or perioperative pain management because the risk of hemodynamic instability (eg, hypotension, bradycardia) may be unacceptable in this population Dilute product with strength of 500 mcg/m L prior to use Epidural: Hemodynamically unstable patients (risk of severe hypotension) Do not discontinue suddenly (risk of rebound hypertension) Patch: May need to remove if severe erythema and/or localized vesicle formation develop at application site or generalized rash; consult physician Severe coronary insufficiency May cause xerostomia Recent MI Cerebrovascular disease Chronic renal failure Raynaud's disease Thromboangiitis obliterans History of depression (may exacerbate depression in cancer patients) May impair ability to perform hazardous tasks Remove patch before MRI (may cause burns) Hypotension may occur; usually responsive to IV fluids and, if necessary, appropriate parenterally administered pressor agents Cardiac conduction abnormalities: Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block, especially if coadministered with other sympatholytic drugs Titrate slowly and monitor vital signs frequently in patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease or chronic renal failure; measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy; avoid concomitant use of drugs with additive effects unless clinically indicated; advise patients to avoid becoming dehydrated or overheated Epidural administration may result in mild respiratory depression (usually with higher than recommended dose) Use with caution in cerebrovascular disease Avoid as first line antihypertensive in the elderly due to high risk for adverse side effects Children may be particularly susceptible to hypertensive episodes when experiencing GI illnesses that lead to vomiting Discontinue oral immediate release formulations within 4 hr of surgery; restart as soon as possible following surgery Due to different pharmacokinetic profiles, oral formulations are not interchangeable with extended release on a mg-mg basis due to different pharmacokinetic profiles Central sympatholytic via stimulation of central alpha receptors; results in reduced sympathetic outflow, causing decreased PVR, HR, BP, and renal vascular resistance; produces presynaptic and postjunctional alpha-2 adrenoreceptor analgesia by preventing pain signal transmission to brain Postsynaptic alpha2-agonist stimulation may regulate subcortical activity in the prefrontal cortex, which may regulate the area of the brain responsible for attention, emotions, and behaviors, and thereby reduces hyperactivity, distractibility, and impulsiveness The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. buy erythromycin canada Many patients with hypertension must use more than one antihypertensive medication to achieve blood pressure control. Drug interactions are possible, especially when patients require medications for other conditions. Flockhart and Tanus-Santos reviewed the drug metabolic effects caused by interactions with the cytochrome P450 microsomal enzyme system in the liver. Researchers have identified specific isoforms of this system that are involved in drug metabolism. Despite some individual variations based on genetic polymorphisms in some isoforms, certain interactions can be predicted. For example, quinidine and diphenhydramine inhibit the CYP2D6 isoform, thereby inhibiting the metabolism of beta-blockers and prolonging negative chronotropic and inotropic effects. Antihypertensive agents also may interact with each other.

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    The apparent nonrenal clearance of clonidine in the CYP2D6 PM subjects lie below the lower limit of the 95% confidence interval for the CYP2D6 EM group. This result confirms that CYP2D6 plays a major role in the oxidative metabolism of clonidine in vivo. antibiotic for uti in cats Antihypertensive action Clonidine decreases peripheral vascular resistance by. Metabolism Metabolized in the liver, where nearly 50% is transformed to. The analgesia is limited to the body regions innervated by the spinal segments where analgesic concentrations of clonidine are present. Clonidine is thought to produce analgesia at presynaptic and postjunctional alpha-2-adrenoceptors in the spinal cord by preventing pain signal transmission to the brain. Absorption

    Usual dose range is 0.2 to 0.6 mg daily in divided doses. If transdermal patch is used, apply to area of hairless intact skin once q 7 days. Half-life of clonidine ranges from 6 to 20 hours in patients with normal renal function. b.i.d.; then increased by 0.1 per day at weekly intervals until desired response is achieved. Excretion: About 65% of a given dose is excreted in urine; 20% is excreted in feces. Initially, clonidine may stimulate peripheral alpha-adrenergic receptors, producing transient vasoconstriction. Antihypertensive action: Clonidine decreases peripheral vascular resistance by stimulating central alpha-adrenergic receptors, thus decreasing cerebral sympathetic outflow; drug also may inhibit renin release. Or, apply transdermal patch (0.2 mg/24 hours) and replace weekly for the first 2 or 3 weeks after smoking cessation. After oral administration, the antihypertensive effect lasts up to 8 hours; after transdermal application, the antihypertensive effect persists for up to 7 days. Contraindicated in patients hypersensitive to drug. Transdermal form is contraindicated in patients hypersensitive to any component of the adhesive layer. C-clonidine was administered orally to dogs (Beagles) for 5 days. 6 radioactive substances eliminated with the urine could be isolated. They were identified by mass spectrometry and comparison with synthetic material. The presence of unchanged clonidine, p-hydroxy-clonidine, and dichlorophenylguanidine was confirmed and 3 new metabolites were detected: 1-(2,6-dichloro-4-hydroxyphenyl)guanidine; 2- [(2,6-dichlorophenyl)imino]imidazolidine-4-one, and 2- [(2,6-dichloro-4-hydroxyphenyl)-imino]imidazolidine-4-one. The cleavage of the imidazolidine ring and the hydroxylation of the phenyl ring are the two principal routes of metabolism. In an additional experiment, the metabolic patterns in the urine of man, rat, and dog were compared after a single oral dose of labelled clonidine. It could be demonstrated that the 6 identified compounds were eliminated by all 3 species, the relative amounts, however, were different.

    Clonidine metabolism

    Catapres Clonidine Side Effects, Interactions, Warning, Dosage., Clonidine hydrochloride - GLOWM

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  3. Jun 22, 2010. Clonidine is a centrally acting, alpha-2 adrenergic agonist used for the treatment of hypertension during pregnancy. The metabolic pathways of.

    • CYP2D6 mediates 4-hydroxylation of clonidine in vitro. - NCBI - NIH
    • CloNIDine Professional Patient Advice -
    • Tips From Other Journals - American Family Physician

    The metabolism of clonidine and related imidazoline derivatives in rat liver. T. A. BAILLIE, D. L. DAVIES, D. S. DAVIES. HELEN HUGHES & ELIZABETH NEILL. azithromycin cipla Absorption of transdermal clonidine can be increased in areas of skin irritation or skin abrasion, so placement of the patches in these areas should be avoided. Clonidine, sold as the brand name Catapres among others, is a medication used to treat high blood pressure, attention deficit hyperactivity disorder.

     
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