Hypertension Mike Clark, M.D.

Hypotension – blood pressure less than 90/60mmg or MAP of 60mmg or less Hypertension – blood pressure of 140/90 or greater

Primary Hypertension – also called Essential Hypertension - no actual cause can be identified for this type of hypertension (90 – 95% of patients have this type) Secondary Hypertension – a cause can be identified

Symptoms General no symptoms Sometimes with accelerated there are headaches, somnolence, confusion, visual disturbances, and nausea and vomiting.

In Primary Hypertension there are no direct causes, there are many risk factors such as sedentary lifestyle, obesity (more than 85% of cases occur in those with a body mass index greater than 25), salt (sodium) sensitivity, alcohol intake, and vitamin D deficiency. It is also related to aging and to some inherited genetic mutations. Family history increases the risk of developing hypertension.

Secondary hypertension is by definition results from an identifiable cause. This type is important to recognize since its treated differently than essential type by treating the underlying cause. Adrenal Cortex (cortisol, aldosterone) Medulla (increased epinephrine and norepinephrine) Renal Cardiac

Hypertension Workup The workup attempts to find if the hypertension is primary or secondary. If secondary, then the type of secondary is sought. History Physical Exam (Cardiac exam) Lab Test (Urine and Blood) EKG Radiology – chest other studies

The cause of hypertension is caused by some change in a component of MAP. Many times that component is not found – thus primary hypertension. MAP = CO x SVR CO = HR x SV SV = EDV – ESV (EDV concerned with blood volume and ESV concerned more with inotropic effect) SVR = ∑R₁ + R₂ + 1/R₃ + 1/R₄ ….. R = 8ŋL/∏r⁴ In order to live – the body compensates by increasing the actions of the organs not affected (homeostasis – negative feedback)

Lifestyle activities that decrease hypertension Weight reduction and regular aerobic exercise (e.g., walking) are recommended as the first steps in treating mild to moderate hypertension. Regular exercise improves blood flow and helps to reduce resting heart rate and blood pressure. Reducing dietary sugar intake. Reducing sodium (salt) in the diet may be effective: It decreases blood pressure in about 33% of people (see above). Many people use a salt substitute to reduce their salt intake. Additional dietary changes beneficial to reducing blood pressure includes the DASH diet (dietary approaches to stop hypertension), which is rich in fruits and vegetables and low-fat or fat-free dairy foods. Discontinuing tobacco use and alcohol consumption has been shown to lower blood pressure. Note that coffee drinking (caffeine ingestion) also increases blood pressure transiently but does not produce chronic hypertension. Reducing stress, for example with relaxation therapy, such as meditation and other mind-body relaxation techniques, by reducing environmental stress such as high sound levels and over-illumination can be an additional method of ameliorating hypertension.

Medications Diuretics Calcium Channel Blockers Angiotensin Converting Enzyme Inhibitors Direct Renin Inhibitors (Aliskiren) Alpha Blockers Beta Blockers

Diuretics Potassium-sparing diuretics These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations: Aldosterone antagonists: spironolactone, which is a competitive antagonist of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. A similar agent is potassium canreonate. Epithelial sodium channel blockers: amiloride and triamterene. Calcium-sparing diuretics The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion of calcium. The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on calcium can be beneficial in hypocalcemia, or unwanted in hypercalcemia. The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics Osmotic diuretics Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.

Figure 9.27

Classes of Calcium Channel Blockers Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance "-dipine". Amlodipine (Norvasc) Nifedipine (Procardia, Adalat) Phenylalkylamine Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed. Verapamil (Calan, Isoptin) Gallopamil (Procorum, D600

Benzothiazepine Benzothiazepine calcium channel blockers are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines. Diltiazem (Cardizem)

Angiotensin Converting Enzyme Inhibitor ACE inhibitors or angiotensin-converting enzyme inhibitors, are a group of pharmaceuticals that are used primarily in treatment of hypertension and congestive heart failure, in some cases as the drugs of first choice. ACE inhibitors can be divided into three groups based on their molecular structure: Sulfhydryl-containing agents Captopril (trade name Capoten), the first ACE inhibitor Zofenopril Dicarboxylate-containing agents This is the largest group, including: Lisinopril (Lisodur/Lopril/Novatec/Prinivil/Zestril) Benazepril (Lotensin) Phosphonate-containing agents Fosinopril (Monopril) is the only member of this group

Alpha Blockers Classification α 1 blockers or antagonists act at α 1 -adrenoceptors α 2 blockers or antagonists - act at α 2 -adrenoceptors When the term "alpha blocker" is used without further qualification, it sometimes refers to α 1 blockers, and sometimes refers to agents that act at both types of receptors. Non-selective α-adrenergic blockers include: Phenoxybenzamine Phentolamine The agents carvedilol and labetalol are both α- and β- blockers. Alpha 2 Blockers used to treat depression

Beta Blockers β 1 -Selective agents Acebutolol (has intrinsic sympathomimetic activity) Atenolol Betaxolol Bisoprolol Celiprolol Esmolol β 2 -Selective agents Butaxamine(weak α-adrenergic agonist activity) - No common clinical utility, used in experimental situations. Non-selective agents Alprenolol Bucindolol Carteolol Carvedilol (has additional α-blocking activity) Labetalol (has additional α-blocking activity) Nadolol Penbutolol (has intrinsic sympathomimetic activity) Pindolol (has intrinsic sympathomimetic activity) Propranolol Timolol