Question

Patient CB has a history of strokes. The patient has been diagnosed with type 2 diabetes, hypertension, and hyperlipidemia. Drugs currently prescribed include the following:

• Glipizide 10 mg po daily
• HCTZ 25 mg daily
• Atenolol 25 mg po daily
• Hydralazine 25 mg qid
• Simvastatin 80 mg daily
• Verapamil 180 mg CD daily

• Explain how the factor you selected might influence the pharmacokinetic and pharmacodynamic processes in the patient from the case study you were assigned.
• Describe how changes in the processes might impact the patient’s recommended drug therapy. Be specific and provide examples.

Answer 1

First factor Glipizide, sold under the brand name Glucotrol among others, is an anti-diabetic medication of the sulfonylurea class used to treat type 2 diabetes.It is used together with a diabetic diet and exercise. It is not indicated for use by itself in type 1 diabetes.It is taken by mouth.Effects generally begin within half an hour and can last for up to a day.

Glipizide sensitizes the beta cells of pancreatic islets of Langerhans insulin response, meaning that more insulin is released in response to glucose than would be without glipizide ingestion. Glipizide acts by partially blocking potassium channels among beta cells of pancreatic islets of Langerhans. By blocking potassium channels, the cell depolarizes, which results in the opening of voltage-gated calcium channels. The resulting calcium influx encourages insulin release from beta cells.

Hypertension is a major modifiable risk factor for stroke, with an estimated 51% of stroke deaths being attributable to high systolic blood pressure globally. The management of hypertension in stroke is determined by timing, the type of stroke, use of thrombolysis, concurrent medical conditions, and pharmacologic variables. We highlight the details of elevated blood pressure management in the hyperacute/acute, subacute, and chronic stages of ischemic stroke and intracerebral hemorrhage.

The relationship between hypertension and stroke is dynamic and multifaceted. Be it in the context of managing ischemic or hemorrhagic stroke, selecting an appropriate blood pressure (BP) agent involves integration of several issues that must be recognized in order to formulate an effective strategy for BP control

Hydrochlorothiazide is a thiazide-type diuretic which has been used clinically for more than half a century. The drug has been widely used to treat hypertension globally and is relatively very safe. Hydrochlorothiazide acts on the distal convoluted tubules and inhibits the sodium chloride co-transporter system. This action leads to a diuretic action and loss of potassium in the urine. The half-life of hydrochlorothiazide varies from 6 to 12 hours. Of the thiazide diuretics, hydrochlorothiazide is the most frequently used for the treatment of hypertension. Unfortunately, over the past decade, the use of hydrochlorothiazide has been declining, and it is being replaced by the angiotensin-converting enzyme inhibitors, which overall are far more effective

Atenolol is one of the most widely used beta blockers clinically, and has often been used as a reference drug in randomised controlled trials of hypertension. However, questions have been raised about atenolol as the best reference drug for comparisons with other antihypertensives. Thus, our aim was to systematically review the effect of atenolol on cardiovascular morbidity and mortality in hypertensive patients.

the need for rapid BP control in both AIS and ICH often requires IV agents. Such agents should be rapidly acting, be easy to titrate, and have few side effects and short half-lives.Some of the commonly used IV medications are nicardipine, labetalol, sodium nitroprusside, nitroglycerine, enalaprilat, and hydralazine. Sodium nitroprusside is not an ideal agent for acute reduction of BP due to its unpredictable dose–response relationship, risk of rebound hypertension, possibility of cyanide toxicity during prolonged use, and potential to cause raised intracranial pressure.

Although hydralazine is used frequently for acute reduction of BP, its use in routine clinical practice is limited due to its selective arteriolar vasodilator effect resulting in reflex tachycardia leading to myocardial injury.

Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke.

Statins lower serum cholesterol level by inhibiting hydroxymethylglutaryl-coenzymeA (HMG-CoA) reductase. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels

the effect of CCBs verapamil on stroke, CCBs reduced stroke more than placebo and β-adrenergic blockers, but were not different than ACEIs and diuretics

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