Amlodipine Besylate Tablets
Amlodipine besylate is a calciumchannel blocker used for the treatmentof hypertension and angina. Under currentclinical definitions of hypertension,calcium channel blockers are introducedat stage 2 (systolic pressure of160 mm Hg or greater or diastolic pressureof 100 mm Hg or greater) generallyin combination with a thiazide diuretic.To minimize the risk of orthostatichypotension, initiation of treatmentwith 2 antihypertensive agents shouldbe done cautiously among patientswith diabetes, the elderly, or patientswith autonomic dysfunction.
The release of Mylan Pharmaceuticals'and Greenstone Ltd's amlodipinebesylate affords clinicians theopportunity to develop creative genericbasedtherapies involving calcium channelblockers, angiotensin-convertingenzyme (ACE) inhibitors, and statins—treatments more often associated withbrand name combination products. Thegeneric equivalent to Norvasc (PfizerInc), amlodipine besylate is available asa single preparation for once-dailyadministration in 2.5-, 5-, and 10-mgstrengths. Mylan Pharmaceuticals is thefirst and only company to receive FDAapproval for its abbreviated new drugapplication for amlodipine besylatetablets. Simultaneous with Mylan'slaunch, Greenstone Ltd, Pfizer's genericsubsidiary, launched its own authorizedgeneric.
Calcium channel blockers such asamlodipine besylate appear to workwell regardless of the ethnicity of thepatient, although African Americansrespond to calcium channel blockersbetter than to ACE inhibitors or betablockingdrugs. This response to drugcategories levels out once a diuretic isadded to the therapy.
Recently, amlodipine besylate hasbeen given additional duties in combinationpreparations. This represents generalacceptance of integrated diseasestates. Although synergy is a conceptwelcomed in drug therapeutics,it is greeted withless enthusiasm whenhypertension and dyslipidemiaare involved. Theseoften-coexistent risk factorscreate damage to thecardiovascular system inexcess of expectations foreither condition alone.
The unwelcome synergybetween hypertension anddyslipidemia can be treatedwith favorable synergism. Combiningamlodipine besylate with atorvastatincreates the branded product known asCaduet. This single-tablet treatment iseffective in reducing both blood pressureand lipid levels.
The use of amlodipine besylate incombination products extends to enhancedactivity against hypertension.For this hybrid, the ACE inhibitorbenazepril is employed.
Proton pump inhibitors (PPIs) and H2-receptor antihistamines are mainstays oftreating disorders of the gastrointestinal(GI) tract. Many H2-receptor antihistaminesare available generically at a substantialsavings to patients, and now varietiesof PPIs are following suit.
Rabeprazole is the latest generic PPI toreach the market. Rabeprazole, thegeneric equivalent of Aciphex (Eisai CoLtd), is available from Teva Pharmaceuticalsas 20-mg tablets.
Most cases of peptic ulcers may occurin the presence of normal acid secretionwhen nonsteroidal anti-inflammatorydrugs or Helicobacter pylori are alsopresent, challenging factors that diminishor disrupt the mucosal defenses presentin the GI tract.
In general, PPIs inhibit gastric acidsecretion through binding at adenosinetriphosphataselevels, the final commonpathway for gastric acid secretion. Allexamples undergo extensivehepatic metabolism, and allare important factors in eradicatingH pylori and treatingpeptic ulcer disease, gastroesophagealreflux disease,Zollinger-Ellison syndrome,and upper GI bleeding.
Ulcers recur in 50% to 90%of patients within a yearwhen single-agent therapy isemployed; this recurrencecan be reduced to as low as10% after a year when amoxicillin orclarithromycin is added to aid in theeradication of H pylori.
The choice of a specific PPI is generallybased on cost, formulation, and overallsafety profile. Since PPIs require activelysecreting proton pumps to be fully effective,dosing should occur 30 minutesbefore a meal, generally breakfast. If asecond dose is required, it should betaken ~10 to 12 hours after this morningdose. Rabeprazole appears unique in itslikelihood to have fewer drug interactionswith caffeine, diazepam, phenytoin,and warfarin than other PPIs. This isthought to be due to its partiallyreversible binding to the proton pumpprocess.
Mr. Middleton is an instructor of pharmacologyat Kellogg CommunityCollege in Battle Creek, Mich.