Pharmacotherapeutics of Hypertension PDF

Pharmacotherapeutics of Hypertension Hypertension Hypertension affects approximately 30-40% of adults aged 20 years and over, which accounts for about 80 million people living in the United States. Despite progress in prevention, detection, treatment and control of high blood pressure, up to 50% are...

Pharmacotherapeutics of Hypertension Hypertension Hypertension affects approximately 30-40% of adults aged 20 years and over, which accounts for about 80 million people living in the United States. Despite progress in prevention, detection, treatment and control of high blood pressure, up to 50% are being inadequately treated and so, hypertension remains a significant public health issue. Factors Involved in Blood Pressure Control The control of blood pressure is complex and involves vascular, cardiac and renal physiology. The three determinates of blood pressure are:  mean arterial pressure  cardiac output  peripheral vascular resistance mean arterial pressure = cardiac output X peripheral resistance The preceding equation should be familiar. According to the equation a decrease in either cardiac output or peripheral resistance will decrease blood pressure. The opposite is true as well. If cardiac output or peripheral resistance is increased so too is blood pressure. Increase cardiac output: increased heart rate, increased contractility, increased sodium and water retention Increased peripheral resistance: vasoconstriction Decreasing one or more of these factors is the goal of antihypertensive therapy Target Organ Damage Hypertension adversely affects numerous organ systems. The treatment of hypertension will decrease the incidence of target organ damage. Clinically, you should note the presence or absence of target organ damage when you evaluate you patient with hypertension. This will influence how aggressively you will manage the hypertension. Results of Hypertension (Target organ damage also referred to as end-organ damage) Organ System Manifestation Cardiac Coronary Artery Disease, left ventricular hypertrophy, cardiac failure Cerebrovascular Transient Ischemic Attacks or stroke Peripheral Vascular Absence of 1 or more major pulses in extremities; intermittent claudication Renal Serum Creatinine > 1.5 mg/dl, proteinuria, 3rd leading cause of dialysis Retinopathy Hemorrhages or exudates, with or without papilledema Drug Therapy for Hypertension Image from Gutierrez 2008 p. 709 Thiazide Diuretics Drugs in this Class  Chlorothiazide (Diuril)  Chlorthalidone (Hygroton)  Hydrochlorothiazide (HCTZ) Mechanism of Action Thiazide diuretics inhibit sodium and chloride reabsorption in the thick ascending loop of Henle and early distal tubule (see diagram below). This loss of ions increases urine volume causing a decrease in plasma volume, which lowers the stroke volume, lowers cardiac output and lowers blood pressure. There is a compensatory increase in peripheral vascular resistance (PVR). Over time, with thiazide use PVR also decreases. This may be because thiazides mobilize sodium and water from arteriolar walls, thus increasing the lumen of arterioles and decreasing peripheral resistance. Adverse Effects: Hypokalemia - about 15% of patients taking 50 mg HCTZ per day will have a potassium of 80 mg/day) may be associated with increased risk of MI and death when given to patients with pre-existing heart disease. Amlodipine and nicardipine are better tolerated than nifedipine. They generally don't cause peripheral edema and are less likely to cause reflex tachycardia. Beta Blockers Drugs in the class: (note suffix or generics  lol)  Selective Beta Blockers o acebutolol (Sectrol) o atenolol (Tenormin) o betaxolol (Kerlone) o bisoprolol (Zebeta) o metoprolol (Lopressor)  Nonselective Beta Blockers o carteolol (Cartrol) o nadolol (Corgard) o penbutolol (Levatol) o propranolol (Inderol)  Combined Alpha 1 and Beta Blocker o carvedilol (Coreg) o labetolol (Trandate) Mechanism of Action: Block beta-adrenergic receptors which reduces the heart rate (negative chronotropic effect) decrease contractility (negative inotropic effect) and thus decrease cardiac output. They also block receptors on the kidneys to reduce the release of renin. Adverse Effects:  bronchoconstriction*  peripheral vasoconstriction*  interference with glycogenolysis*  bradycardia  exacerbation of heart failure  fatigue  depression  sleep disturbance Clinical Use In Hypertension:  has been widely used antihypertensive drug, second only to diuretics – however, new JNC VIII recommend use only with compelling reasons or co-morbidities such as post MI  convenient to take QD or BID dosing  useful to treat patients with concomitant diseases (angina, post MI, migraines, hyperthyroidism symptoms)  * Avoid use of beta blockers in patients with peripheral vascular disease, asthma or history of COPD  beta blockers should be use with caution in diabetics receiving hypoglycemic treatment because they inhibit the normal sympathetic response to hypoglycemia. Alpha-1 Receptor Blockers Drugs in this class: (note the suffix in the generics  zosin  doxazosin (Cardura)  terazosin (Hytrin)  prazosin (Minipress) Mechanism of Action: Alpha blockers reduce arterial pressure by blocking peripheral post-synaptic alpha-1 receptors and decrease total peripheral resistance Adverse Effects:  first dose syncope/ orthostatic hypotension  dizziness, drowsiness, headaches Clinical Use:  According to the ALLHAT trial when compared to thiazide diuretic (chlorthalidone), the arm of patients on alpha-1 blockers had 25% higher incidence of major cardiovascular disease events than those in the thiazide arm.  This class of drugs should not be used as initial monotherapy for HTN  Use to treat mild to moderate HTN  Terazosin (Hytrin) is also labeled for use in the treatment of benign prostatic hyperplasia. Alpha-2 Agonists Drugs in this class:  clonidine (Catapres)  guanabenz (Wytensin)  guanfacine (Tenex)  methyldopa (Aldomet) Mechanism of Action: work by stimulating alpha-2 receptors in the brainstem, decreasing sympathetic outflow to the heart, kidneys and peripheral vasculature. This inhibits release of norepinephrine and lowers BP. Adverse Effects:  Since these drugs work directly on the CNS, these are the most common adverse effects: sedation, drowsiness, dry mouth  GI adverse effects include dry mouth, constipation, abdominal pain  Impotence and decreased libido  Rebound hypertension can occur if the drugs are discontinued suddenly. When discontinuing these meds it is important to taper the dose over one - two weeks  Rash - clonidine is available in a weekly transdermal patch, which in theory is very convenient, but up to 40% of patients develop a rash. Clinical Use:  Not generally used as first line to treat HTN due to the CNS effects  Methyldopa - drug of choice in pregnancy-induced hypertension Therapeutic Approach To Hypertension For the NPs: Hypertension will be discussed extensively in your upcoming clinical management courses, so stay tuned. Images from Gutierrez 2008, p. 710 and 730. See next page for the JNC VIII treatment algorithm