Captopril about

Neutropenia/Agranulocytosis Neutropenia (less than 1000/mnr ) with myeloid hypoplasia resulted from captopril use. About half of the neutropenic patients developed systemic or oral cavity infections or other features of agranulocytosis. Neutropenia/agranulocytosis has occurred rarely with enalapril or lisinopril and in 1 patient on quinapril. Data are insufficient to show that moexipril, ramipril, quinapril, benazepril, trandolapril, orfosinopril do not cause agranulocytosis at similar rates. Periodically monitor WBC counts. 

The onset of action following oral administration of captopril is about 15 minutes, with peak blood levels achieved in 30 to 60 minutes. Its apparent biological half-life is approximately 2 hours, with its antihypertensive effects observed for 6 to 10 hours. The kidneys appear to play a major role in the inactivation of captopril. 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

The potency of captopril (14) as an inhibitor of ACE depends critically on the configuration of the mercaptoalkanoyl moiety the compound with the S-configuration is about 100 times more active than its corresponding R-enantiomer [37], The required 3-mercapto-(25)-methylpropionic acid moiety has been prepared from microbially derived chiral 3-hydroxy-(2R)-methylpropionic acid, which is obtained by the hydroxylation of isobutyric acid [38-40],... 

The doctor decides to prescribe Sam an angiotensin-converting enzyme (ACE) inhibitor, captopril. However, a few weeks later Sam is back, complaining about his throat and a dry, hacking cough, which disrupts his business discussions and, worse,... 

Disposition in the Body. Readily absorbed after oral administration about 75% of the dose is absorbed. Up to 40% of an oral dose is excreted in the urine as unchanged drug, about 3% as captopril disulphide and about 30% as polar metabolites. Excretion in the urine is rapid, about half the dose being excreted within the first 4 hours. An 5-methyl metabolite has been identified in plasma and urine. 

There have been numerous reports of different rashes in association with ACE inhibitors. The most common skin reaction is a pruritic maculopapular eruption, which is reportedly more common with captopril (2-7%) than with enalapril (about 1.5%). This rash occurs in the usual dosage range and is more common in patients with renal insufficiency (70). Lichenoid reactions, bullous pemphigoid, exfoliative dermatitis, flushing and erythroderma, vasculitis/purpura, subcutaneous lupus erythematosus, and reversible alopecia have aU been reported (70-72). 

An 86-year-old man, who was taking captopril 25 mg bd and bendroflumethiazide 25 mg/day for hypertension, had a transurethral resection of the prostate under spinal anesthesia, and developed profound bradycardia and hypotension with disturbances of consciousness during transfer to the recovery room (18). Initial treatment with atropine produced rapid improvement in cardiovascular and cerebral function. A further hypotensive episode, without bradycardia, occurred about 1 hour later, but responded rapidly to methoxamine. He made a full recovery overnight. 

The determination of plasma renin responsiveness, however, is not sufficient to diagnose primary aldosteronism because suppressed PRA also occurs in about 25% of patients with essential hypertension. Primary aldosteronism can be differentiated from other hypermineralocorticoid states on the basis of inappropriate secretion of aldosterone. The demonstration of an elevated concentration of aldosterone in blood or urine in a patient with an unequivocally suppressed PRA concentration (a plasma aldosterone/ plasma PRA ratio >50) is presumptive evidence of primary aldosteronism. Because hypokalemia has a suppressive effect on aldosterone secretion, the potassium deficit should be replaced before aldosterone measurements are done. To establish aldosterone autonomy, the clinician may attempt to suppress aldosterone production with rapid volume expansion (see Box 51-10), with a potent mineralocorticoid (see Box 51-11), or as mentioned with captopril. Failure... 

Information learned from the synthesis of teprotide and an increasing knowledge about ACE, another compound, captopril, was synthesized then followed by a number of other ACE inhibitors. US Food and Drug Administration (FDA) approval came in the early 1980s. Captopril was... 

Ms Thomas is a 52-year-old lady of African origin. She has hypertension for which she has been prescribed captopril. Ms Thomas wants to know if she should expect any side effects from this drug. She is particularly worried about her sensitive stomach. What can you tell her about side effects with captopril and is there any other advice you could give her about this medication ... 

Sample preparation 5 mL Urine + 2 mL 500 mM pH 7.0 phosphate buffer -I- 0.5 mL 20 mg/mL p-bromophenaaqueous layer and add it to 100 p-L 2% tributylphosphine in MeOH, heat at 50°for 30 min, wash with 6 mL hexane, add 200 p,L 0.2% N-(4-dimethylamino-3,5-dinitrophenyDmaleimide in acetone to the aqueous layer, mix, let stand at room temperature for 5 min, wash with 6 mL hexane, discard the hexane layer, acidify the aqueous layer with about 200 pL 2 M HCl, extract twice with 6 mL portioiis of benzene (Caution Benzene is a ceircmogen ). Combine the organic layers and add 10 pg IS, evaporate to dryness imder reduced pressure, reconstitute the residue in 200 pL MeOH, inject a 5-20 pL aliquot. (Free captopril is derivatized as its p-bromophenaQrl bromide adduct then oxidized captopril is reduced and derivatized as its N-(4-dimethylamino-3,5-dinitro-phenyl)maleimide adduct.)... 

The modern blockbuster products era started four decades ago with Valium (Roche, diazepam), which was the most prescribed global medicine between 1969 and 1982 with 2.3 billion doses taken in 1978 and the first medicine to achieve peak sales of 200 million. It was later joined by benzodiazapine, antibiotics, and non-stroidal analgesics and by several innovative medicines like Captopril, Capoten, and Mevacor in the 1980-1990 period [9-13]. The period of billion-dollar pharmaceutical brands started 10 years ago and of biotechnology brands about 5 years ago. A commercial report estimated the total blockbuster medicine sales in 2005 at 145 billion and forecasted strong growth in biologies [14]. 

As in the case of aqueous solutions of captopril (15) and enalapril (16), signals attributable to rotamers (rotation about the lysyl-proline tertiary amide bond) are observed in the spectrum of lisinopril. The triplets at 4.62 ppm and 4.13 ppm represent, respectively, the C2 and C2. protons in the minor rotamer. 

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