,

therapy

~·BLOCKERSOFFER SIMPLER REGIMENS IN HYPERTENSION

Patientcompliance in long-term antihypertensive therapy is generally considered unsatisfactory. The searchfor an effective, well.tolerated,singledaily-dose regimen,with no serious or debilitating side-efTects, for the control of mild or moderateessentialhypertensionis highlighted by 3 articlesfrom India, Great Britainand South Africa.

• Adequate Control with Once-A-Day PenbutololIn a IO-week trial on 10 middle-aged patients(resting diastolicBPof 100 to 120mm Hg),a once-a-day doseof 50mg penbutololproduceda final restingdiastolic BPof 90mm Hg in 6 patients, althoughall patientshad a fall in BPof at least IOmm Hg, theeffectlastingfor 24 hours [I]. No untoward side-effects or postural hypotension were reported. 25mg penbutololwas givenafterbreakfastand the doseof the drug was doubledevery 3 weeks for 8 patients.The other 2 patients took 25mg for 3 weeks followedby 50mg for 6 weeks.Significant reductions in supine and standingBPwere recorded on a single 25mg dose, further increasedwi>' 50mg in allpatients.No further significantreductionin supinediastolic pressure was recorded with IOOmg penbutoloI.

Atenolol•• J a 16-weeIC randomised, double-blind, cross-over trial on I9 middle-aged patients(supinediastolicpressureabove 90mm Hg),atenololin once-daily dosesof 50, 100.and 200mg producedan averageof 20mm Hg reductionof supine systolicBP in 12, 14'and 13 patientsand an averagereductionof IOmmHg supinediastolicBP in 15, 15 and 13 patients, respectively. No significantdifference was noted in the supine,standingor post-exercise BP with higherdoses[2].Patients were given50, 100 or 200mg atenololor placebo at 18.00hours oncea day for 4 weeks. Mean bloodlevelsof atenololatthe endof 4 weeks' therapy, 20 to 23 hours after the last doseof the drug, were0.06 ± 0.0 1,0.11 ± 0.02, 0.16 ± O.02jJg/ ml with50, 100and 200mg atenololrespectively. Supineand standing pulserates after 4 weekswere significantlylower with IOOmg thanwith 50mg(p<0.05 and p <0.01 respectively). Duration of the reductionin BPoutlastedthe duration of reductionin pulse rateobtainedwith 50mg atenolol.

• And with a Combination Tablet of Timolol + DiureticIn 12 middle-aged patients(averagesupinediastolicBP 105 to l30mm Hg)one tabletof'Moduretic' (I Omg timolol maleate,25mg hydrochlorothiazide arid25mg amiloride) givenat 8am after breakfast, produceda significantfall in supineand erectBPwhich was sustainedover a periodof24 hours. No adverseside-effects or abnormal changesin bloodbiochemistrywere noted[3].Patientstook placebo for 14 days followed by one 'Moduretic' tablet for 14 days increasedto two 'Moduretic' tabletsif the supinediastolicBP was still 90mm Hg (7 patients). Patientpulse rates droppedan averageof 10bpm,the greatest fallbeing with 2'Moduretic' tablets.Bloodpressures fluctuated throughout the day, no set diurnal pattern was elicited with either placebo or'Moduretic' , Supinearterialpressure at 8am fellfrom 172/ III to 148/96mm Hg.

[I) Sainani, G.S. et al.: Pharmatherapeutica I: 493 (No 8, 1977)

[2) Jeffers, T.A. et al.. British Journal of Clin ical Pharmacology 4: 523 (Oct 1977)[3) Leary, W .P. et al.. Current Therapeutic Research 22: 385 (Sep 1977)

INPHARMA 22nd October. 1977 p8