Anti-Hypertensive Drugs PDF

ANTI-HYPERTENSIVE DRUGS Overview Examples Mecahnism of action —-Route of Administeration Pharmacokineti cs Pharmacodyna mics Indications...

ANTI-HYPERTENSIVE DRUGS Overview Examples Mecahnism of action —-Route of Administeration Pharmacokineti cs Pharmacodyna mics Indications Contraindicatio ns Drug interactions Toxicity Overview of Hypertension Hypertension is when the force of blood pushing against your artery walls is consistently too high. This damages your arteries over time and can lead to serious complications like heart attack and stroke. Getting your blood pressure checked is the only way to know if it’s too high. You can do this by seeing a healthcare provider for a yearly checkup, even if you feel healthy. You won’t feel sick if you have high blood pressure. So, these checkups are crucial and can be life- saving. If your BP is above the normal range, your provider will recommend lifestyle changes and/or medications to lower your numbers.  Blood pressure higher than 180/120 mm Hg is considered a hypertensive emergency or crisis. Seek emergency medical help for anyone with these blood pressure numbers. Untreated, high blood pressure increases the risk of heart attack, stroke and other serious health problems. It's important to have your blood pressure checked at least every two years starting at age 18. Some people need more-frequent checks. Healthy lifestyle habits —such as not smoking, exercising and eating well — can help prevent and treat high blood pressure. Some people need medicine to treat high blood pressure.  Blood pressure medications (antihypertensives) are medicines that bring your blood pressure down in various ways. Some blood pressure medications make your blood vessels widen so blood gets through more easily. Others remove extra fluids from your blood or block natural hormones your body makes that raise blood pressure. In addition to your age, race and gender/sex, your healthcare provider will consider your other health problems and how high your blood pressure is when deciding which high blood pressure medication to give you. Your treatment will be different from your neighbor’s or your brother’s prescriptions because each of you has a unique situation.  You may need to take more than one type of high blood pressure medication to bring your blood pressure numbers down. Your healthcare provider may try one antihypertensive agent and add a second or third little by little to bring your blood pressure down. They may also start and stop antihypertensive drugs if they aren’t giving results or you develop intolerable side effects or unsafe changes in your bloodwork. Your healthcare provider will likely ask you to take your blood pressure at home each morning, before you have had any caffeine. Most people take blood pressure medications in the form of a pill you swallow every day, but your doctor may give you some antihypertensive medications through an IV (intravenous) in your arm during a hospital stay. Examples, their mechanism of action and side effects Here are examples of anti-hypertensive drugs, classified by their mechanism of action: Diuretics Mechanism of action: They help your blood vessels get wider and make your kidneys move extra fluid and salt into your urine.All diuretics except mannitol and vasopressin receptor antagonists function initially by blocking sodium reabsorption in various sites within the renal tubules, leading to increased fractional excretion of sodium and natriuresis. Most diuretics, including loop diuretics, thiazide diuretics, amiloride, triamterene and carbonic anhydrase inhibitors, act on transporters located on the luminal surface of nephron tubules. Examples include: 1. Hydrochlorothiazide (HCTZ) 2. Furosemide (Lasix) 3. Spironolactone (Aldactone) 4. Amiloride (Midamor) 5. Triamterene (Dyazide) Thiazide diuretics, such as hydrochlorothiazide (Microzide® or Oretic®) or chlorthalidone (Hygroton® or Thalitone®). Action: They make your kidneys pull salt and extra water into your pee. Side effects: Headache. Loss of appetite. Hair loss.  Loop diuretics, such as furosemide or bumetanide. Action:They affect part of your kidneys (the loop of Henle) to get salt and excess water out of your body. Side effects: Dizziness. Diarrhea. Upset stomach. Potassium-sparing diuretics, such as triamterene or amiloride. Action: They help your kidneys clear salt and water out of your body, but don’t let you lose too much potassium in the process. Side effects: Gas. Nausea. Headache.  Route of Administration Diuretic administration is usually via the oral route, but when maximum potency is required, such as in cases of advanced HF, it can be given intravenously in a hospital setting. In such situations, continuous infusion over a specified period is preferable to bolus injections. Adverse effects (or complications) in a particular patient should be well-anticipated, and the choice of diuretic, the dose required, route of administration, and needed clinical improvement, should all merit consideration before administering any diuretic agent.  Pharmacokinetics Hydrochlorothiazide is 65% absorbed in healthy fasting subjects and 75% absorbed when given with food. The increased uptake appears to be caused by decreased gastric emptying rate. Absorption is impaired in patients who have undergone intestinal shunt surgery and in some patients with cardiac failure. Plasma half-life averages 10h in subjects with normal renal function. It is prolonged in renal failure as the drug is mainly eliminated via the kidneys in unchanged form. The bioavailability of hydroflumethiazide is at least 50%. Elimination half-life is about 17h in normal subjects and 10h in patients with cardiac failure. The drug is largely eliminated unchanged in the urine. The half-life of poly thiazide is approximately 26h. A bout 20% of an oral dose is cleared via the kidneys.  Bumetanide is completely absorbed. Up to 96% is bound to plasma proteins. Apparent volume of distribution ranges from 12 to 35L. Plasma half-life is 1.2 to 1.5h in healthy subjects and does not appear to be prolonged in renal failure. Renal and non-renal clearance contributes equally to its elimination. The uptake of frusemide (furosemide) from the gastrointestinal tract is about 65% and is decreased in uraemia and nephrosis. Protein binding is 96 to 98% and is diminished in nephrosis. Plasma half-life is approximately 50 minutes in healthy subjects and is prolonged about 3 times in renal failure. Apparent volume of distribution (Vdβ) ranges from 14 to 17L. Urinary excretion and non-renal elimination contribute almost equally to plasma clearance. The uptake of amiloride is at least 50% and is diminished when given with food. Plasma half-life averages 10h. Amiloride is essentially eliminated unchanged in the urine.  Pharmacodynamics They help your blood vessels get wider and make your kidneys move extra fluid and salt into your urine.All diuretics except mannitol and vasopressin receptor antagonists function initially by blocking sodium reabsorption in various sites within the renal tubules, leading to increased fractional excretion of sodium and natriuresis. Most diuretics, including loop diuretics, thiazide diuretics, amiloride, triamterene and carbonic anhydrase inhibitors, act on transporters located on the luminal surface of nephron tubules.  Indications Different classes of diuretics have distinct pharmacokinetic and pharmacodynamic properties and varying mechanisms of action. Therefore, indications for their use vary. Loop diuretics are typically the first choice for edematous disorders, such as cardiac failure, nephrotic syndrome, and hepatic cirrhosis, as well as for blood pressure and volume control in patients with advanced chronic kidney disease. Thiazides are considered first-line therapy to treat patients with uncomplicated hypertension. Potassium-sparing diuretics are most commonly used to correct potassium deficiency in patients with hypertension or to treat conditions of aldosterone excess, as is the case with aldosterone antagonists. Carbonic anhydrase inhibitors are primarily used to treat glaucoma. Osmotic diuretics are the first choice for cerebral edema.  Contraindications Severe dehydration or established anuria is a contraindication for any type of diuretic. Patients with known hypersensitivity to any of the diuretic agents are contraindicated to receive the same drug. Diuretics are contraindicated in severe electrolyte derangement and should not be administered until a detected electrolyte abnormality is corrected. Loop and thiazide diuretics are contraindicated in patients already diagnosed with gout. Loop diuretics (except ethacrynic acid), thiazide diuretics, and CAIs are all sulfonamide derivatives and were generally regarded as contraindicated in sulfa-allergy patients. Recent evidence suggests otherwise, and several reports of instances of uneventful use of sulfa-diuretic use in documented sulfa-allergy patients exist. In conclusion, only a low risk of cross-allergenicity between sulfonamide antibiotics and sulfonamide non-antibiotics and diuretics can be prescribed with caution in sulfa-allergic patients. Notwithstanding, documented allergy to any of the sulfonamide diuretic agents themselves should be considered an absolute contraindication, and for sulfonamide non-antibiotics, it is a relative contraindication. loop diuretics are contraindicated in patients with hypokalemia (only to be administered after correction), severe hyponatremia, hypotension, azotemia, oliguria/anuria, and hepatic coma. It is also contraindicated in any situation where fluid depletion is foreseen, such as surgery. Furosemide and bumetanide are pregnancy category C, while torsemide is category B and relatively safe in pregnancy.  Thiazide diuretics induce hyperglycemia, but are these agents contraindicated in hypertensive patients for the risk of new-onset diabetes or worsening of preexisting diabetes? Thiazides are of crucial importance as first-line therapy in patients with hypertension, a condition treated primarily to reduce the high risk of CV mortality. To compare the two important drugs in this class, chlorthalidone (thiazide-like diuretic) has demonstrated superiority to hydrochlorothiazide (thiazide-type diuretic) in reducing systolic BP levels and in achieving target BP values. Also, in comparison to other anti-hypertensives, chlorthalidone has been repeatedly shown in various clinical trials to greatly reduce the risk of adverse CV events. Also, chlorthalidone has been shown to cause the fewest clinical events of diabetes in contrast to any other anti-hypertensive. In a hypertensive population with preexisting diabetes, the salutary anti-hypertensive effects of low-dose (12.5 mg) chlorthalidone outweigh the risk of glucose intolerance and will particularly benefit young non-obese patients. The 2018 ESC guidelines on hypertension give the highest class I recommendation for the use of thiazide/thiazide-like diuretics along with a RAS blocker in the treatment of diabetics with hypertension. Guidlines advised against the use of thiazides in patients with severe stage 4 or stage 5 CKD (see Table 2), though recent reports are in favor of its use as anti-hypertensive (even if GFR less than 30 mL/min) as the BP- lowering mechanism of thiazides are not related to their diuretic function in the kidney. Nevertheless, thiazides are contraindicated when the diuresis is the predominant action required in patients with CKD, where loop diuretics are preferred. The only exception is metolazone, a thiazide diuretic that can be used for diuresis in CKD. K+-sparing diuretics are contraindicated in hyperkalemia (K+ levels more than 5 mEq/L) until the underlying pathology is corrected. PSDs are contraindicated in advanced renal failure or CKD as these patients are at risk of hyperkalemia; this is particularly true when GFR