Clonidine hydrochloride and

Procedure Dissolve 0.2 g of clonidine hydrochloride in 70 ml of ethanol (96%) and titrate with 0.1M ethanolic sodium hydroxide Vs determining the end-point potentiometrically. Each ml of 0.1 M ethanolic sodium hydroxide Vs is equivalent to 26.66 mg of C9H9C12,N3, HC1. 

Part—III exclusively treats Electrochemical Methods invariably and extensively used in the analysis of pharmaceutical substances in the Official Compendia. Two important methods, namely potentiometric methods (Chapter 16) deal with various types of reference electrodes and indicator electrodes, automatic titrator besides typical examples of nitrazepam, allopurinol and clonidine hydrochloride. Amperometric methods (Chapter 17) comprise of titrations involving dropping-mercury electrode, rotating—platinum electrode and twin-polarized microelectrodes (i.e., dead-stop-end-point method). 

Levinson, M.L. and Johnson, C.E. (1992) Stability of an extemporaneously compounded clonidine hydrochloride oral liquid. Am J Hosp Pharm 49 122-125. 

Clonidine. As with the rationale for P-blockers in the treatment of social phobia, clonidine hydrochloride, an a-adrenergic agonist, has been used in an attempt to target the physiological symptoms of the disorder. In a case report by Goldstein [1987], one subject with social phobia who experienced a primary symptom of blushing was treated with clonidine 0.1 mg twice a day after trials with alprazolam, phenelzine, and propranolol failed to provide symptom relief. The patient reported a dramatic decrease in the frequency and intensity of blushing episodes after 1 week of treatment. At 4-month follow-up, his symptoms remained well controlled and he denied any side effects. 

Clonidine hydrochloride (Catapres), carbamazepine (Tegretol), and methylphenidate (Ritalin) are occasionally useful in intractable cases of migraine. Cyproheptadine (Periactin) may be effective in adults with migraine it is of considerable importance in the treatment of childhood migraine, and many consider it to be the drug of first choice. Dosages range from 4 to 3 mg, three to four times a day, in adults and 4 mg, two to three times a day, in children. 

An interesting example is die assay of clonidine hydrochloride in injections and tablets (British Pharmacopoeia, 1980). In 0.01 Mhydrochloric acid, clonidine exhibits two sharp maxima ne - 272 nm and 279 nm, which are not suitable for precise measurement. However, clonidine forms an ion pair with bromothymol blue, and this can be readily extracted into chloroform for subsequent measurement of the broad maximum near 420 nm. Because of the intiinsic variabihty of reagents used in such methods, a pharmacopoeial reference standard is employed for cahbration. A similar policy is adopted for assays involving chemical modification of the drug, as in the tetrazolium assay for corticosteroids, the assay for folic acid involving hydrolysis, diazotisation, and coupling with N-(l-naphthyl)ethylenediamine, and the reaction of penicillins with imidazole and mercuric salts. 

Aldocolor combines methyldopa, 68, and chlorthiozide, 69. Clorpes is a combination of clonidine hydrochloride, 70 (a centrally acting antihypertensive agent), and chlortholidone, 71 (a diuretic). 

The effects of exposure to clonidine hydrochloride in children, as reported to US poison centers from 1993 to 1999, have been retrospectively reviewed (41). There were 10 060 reported exposures, of which 57% were in children under 6 years, 34% in children aged 6-12 years, and 9% in adolescents aged 13-18 years. 

Clonidine hydrochloride has advantages over antihyper-icnsive drugs such asguanethidinc monosulfate and prazosin hydrochloride, in that it seldom produces orthostatic hypo-icndvc side effects. It does, however, have some sedative properties that ate undesirable it also may cau.se constipa-ilnn and dryness of the mouth. 

Catapres (Clonidine Hydrochloride USP) and Tenex (Guanfacine Hydrochloride)... 

CLONIDINE HYDROCHLORIDE/ CHLORTHALIDONE (Clorpres tablets 0.1 mg clonidine and 15 mg chlorthalidone)... 

Examples. Clonidine hydrochloride, hydralazine hydrochloride, methyl-dopa, diaoxide and sodium nitroprusside. 

Clonidine hydrochloride is an inidazoline derivative hypotensive agent (1) which is thought to act through the central nervous systea to elicit a hypotensive response (2). Although the locus of action in the central nervous systen is unlcear, clonidine has been shown to be a potent a-adrenergic agonist in both central and peripheral systems (3). 

Clonidine hydrochloride is an antihypertensive agent, whose mechanism of action appears to be central a-adrenergic stimulation. This result in the inhibition of bulbar sympathetic cardioaccelarator and sympathetic vasoconstrictor centers, therapy causing a decrease in sympathetic outflow from the brain. Initially drug stimulates pheripheral a-adrenergic receptors producing transient vasoconstriction (5). 

Cody et al. (11) also determined the crystal structure of clonidine hydrochloride in order to determine the conformation of protonated clonidine and to elucidate the relationships between its structure and that required for binding to the a-adrenergic receptor. 

Table (2). Distances (A) and angles (°) in the crystals of clonidine hydrochloride...

C-NMR spectrum (12) of clonidine hydrochloride Fig. (7-9) was recorded in DMSO-de by Varian XL-200 MHz NMR spectrometer. The multiplicity of the resonances was obtained from DEPT (Distortionless enhancement by polarization transfer) and APT (attached proton test). The carbon chemical shifts are presented in Table (7). 

The mass spectrum (12) of clonidine hydrochloride obtained by electron impact ionization (Fig. 10) was recorded on a Finnigan MAT 90 mass spectrometer. The spectrum was scanned from 50 to 500 a.m.a. The electron energy was 70 ev. Emission current 1 mA and ion source pressure 10 torr. The spectrum shows a... 

Reduction in blood pressure is meiximal at plasma clonidine concentrations less than 2 ng/mL. Blood pressure begins to decrease within 30-60 minutes after an oral dose of clonidine hydrochloride, the maximum decrease occurs in approximately 2-4 hours. The hypotensive effect lasts up to 8 hours. Following administration of clonidine by slow intravenous injection in patients with acute hypertensive crises, a hypotensive effect occurred within minutes, peaked in 30-60 minutes and lasted more than 4 hours (1). 

In humans 65 % of administered dose of clonidine hydrochloride is excreted by the kidneys, 32 % as unchanged drug and the remainder as inactive metabolites. Approximatly 20 % of dose is excreted in feces, probably via entrohepatic circulation. Approximately 85 % of a single dose is excreted with 72 hours and excretion is complete after 5 days (1). 

Clonidine hydrochloride is used in the treatment of grades of hypertension. The usual initial dose of clonidine hydrochloride is 50 to 100 pg orally thrice daily increased every second or third day according to the response of the patient. The usual maintenance dose is 0.3 to 1.2 mg daily but doses of up to 1.8 mg or more daily may be required. To reduce side effects a similar dose of clonidine may be given in conjunction with a thiazide diuretic but combination with a 13-blocking agent should be avoided where possible clonidine may also be given in a sustained-release formulation which enables twice-daily dosage, or by a transdermal delivery system which is applied once a week and delivers 100-300 pg daily at a constant rate (4). 

Clonidine hydrochloride has been used topically to reduce intraocular pressure in the treatment of open angle (chronic simple) and secondry glaucoma and hemorrhagic glaucoma associated with hypertension (1). 

Sane (15) developed a method for the estimation of clonidine hydrochloride in pharmaceutical preparations by ion pair extraction and colorimetric method. An acid-dye complexing method with bromophenol blue, bromocresol purple and methyl-orange was used for the ion-pair extraction and colorimetric determination of clonidine hydrochloride in pharmaceuticals containing 100 mg of clonidine hydrochloride was 98.9X and relative standard deviation 0.89X. 

Dissolve 50 mg of clonidine hydrochloride in a mixture of 10 ml of acetone and 40 ml of 0.5 M sod. carbonate solution. Transfer to a 50 ml flask make up to the mark with dansyl chloride and acetone was added and then 4-methyl pentan-2-one was added. Fluorescence intensity was measured after 10 minutes at 455 nm using an excitation wavelength of 345 nm. 

A simple and rapid spectrophotometric method (16) based on the reaction of clonidine hydrochloride with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone to form a colored product with maximum absorption at 455 nm. 

Accurately weighed amount of clonidine hydrochloride equivalent to 50 mg of the base was dissolved in about 20 ml distilled H2O, made alkaline with few drops of 10% w/v NaOH solution and extract with five successive 10 ml portions of chloroform. Pass the chloroform extracts sequentially over anhydrous sod. sulphate and collect the combined chloroform extracts in 50 ml flask make up to volume with chloroform. Heat and dissolve in acetonitrile and 2 3-dichloro-5,6-dicyano-l,4-benzoquinone and measured at 455 nm against blank. 

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