Drugs Acting on the Cardiovascular System PDF

DRUGS ACTING ON THE CARDIOVASCULAR SYSTEM The cardiovascular system is a closed system that circulates oxygenated blood to the body’s tissues and removes waste. Blood flows from high pressure areas to low pressure areas. The left ventricle has the highest pressure, pumping blood into the a...

DRUGS ACTING ON THE CARDIOVASCULAR SYSTEM The cardiovascular system is a closed system that circulates oxygenated blood to the body’s tissues and removes waste. Blood flows from high pressure areas to low pressure areas. The left ventricle has the highest pressure, pumping blood into the aorta. The right atrium has the lowest pressure, collecting deoxygenated blood. The brain and hormones regulate blood pressure. High blood pressure is hypertension, and low bp is hypotension. Severely low blood pressure (shock) is life threatening. Drug therapy aims to keep blood pressure within a healthy range. Blood Pressure Control Blood pressure is maintained within a normal range by complex system involving the brain, hormones and specialized cells called baroreceptors. Baroreceptors, located in the aorta and carotid arteries, detect blood pressure changes. High BP-if the pressure is too high, baroreceptors signal the brain to cause vasodilation (widening of blood vessels) and a decrease in heart rate, lowering blood pressure. Low BP-if the blood pressure is too low, baroreceptors signal the brain to cause vasoconstriction (narrowing of blood vessels) and an increase in heart rate, raising the blood pressure. This entire process is mediated by the autonomic nervous system. Three key factors determine blood pressure includes: Heart rate, stroke volume (amount of blood pumped per heartbeat), and total peripheral resistance (resistance in blood vessels). Small arterioles play a significant role in peripheral resistance due to their small diameter. Severe low blood pressure is called shock and is life-threatening condition. Drug therapy aims to keep blood pressure within the normal range. Renin-Angiotensin-Aldosterone System The RAS is a compensatory mechanism that helps maintain blood flow to the kidneys when blood pressure drops. Low BP or poor oxygenation triggers the release of renin. Renin converts angiotensinogen to angiotensin I, which is then converted to angiotensin II in the lungs. Angiotensin II causes vasoconstriction, raising BP. It also stimulates the adrenal cortex to release aldosterone, which increases sodium and water retention, further increasing blood volume and BP. This increased BP restores blood flow to the kidneys, completing the feedback loop. Hypertension Essential hypertension – 90% of hypertension cases are “essential”, meaning there is no known cause. People with this type usually have increased peripheral resistance but no symptoms. Secondary hypertension – a smaller percentage of cases result from a known cause, such as pheochromocytoma (presence of tumor at the adrenal medulla). Hypertension if untreated could be dangerous and be considered to be “the silent killer”. Prolonged high blood pressure damages blood vessel linings, leading to thickening and reduced responsiveness. This increased workload on the heart raises the risk of coronary artery disease (CAD), cardiac death, stroke, renal failure and vision loss. Because hypertension often has no symptoms, its difficult to diagnose and treat. Many factors contribute to hypertension, including stress, high-frequency noise, high salt diets, lack of rest and genetics. Hypotension Hypotension (low blood pressure) occurs when blood pressure drops too low, preventing vital organs (especially brain) from receiving enough oxygenated blood. This can lead to shock, where waste products build up and cells die from oxygen deprivation. Hypotension can be caused by: Heart damage wherein the heart cannot pump blood effectively, severe blood loss or fluid loss because significant volume loss lowers blood pressure and depletion of norepinephrine (a hormone that raises blood pressure) during extreme stress can cause hypotension. ANTIHYPERTENSIVE AGENTS Angiotensin-Converting Enzyme Inhibitors Actions and Indications: ACE inhibitors work in the lungs to block the conversion of angiotensin I to angiotensin II (a powerful vasoconstrictor). This lowers blood pressure, slightly increases serum potassium and decreases serum sodium and fluid. These drugs treat hypertension, sometimes with other medications. They are also used with digoxin and diuretics for heart failure and left ventricular dysfunction. Their benefit is thought to come from reduced cardiac workload, peripheral resistance and blood volume. They are also approved for diabetic nephropathy likely by reducing stimulation of angiotensin receptors in the renal artery, thus slowing the damage. Pharmacokinetics: ACE inhibitors are typically administered orally. Enalapril can also be given parenterally if oral administration is not possible or a quick effect is needed. These drugs are well absorbed and distributed throughout the body, metabolized in the liver and excreted on the urine and feces. Can cross the placenta and breastmilk posing serious birth defects. Therefore, ACE inhibitors should not be used during pregnancy. Contraindications and Cautions: ACE inhibitors should not be used by people allergic to them to prevent severe reactions. They should not be used in those with impaired kidney function or heart failure, as the drug could worsen these conditions. Women of childbearing age using ACE inhibitors should use birth control to avoid pregnancy, as the drug can harm the fetus. The drug is also contraindicated during breastfeeding due to potential effects on milk production and the baby. Adverse Effects: Are related to the effects of vasodilation and alterations in blood flow. Such effects include reflex tachycardia, chest pain, angina, heart failure and cardiac arrythmias, GI irritation, ulcers, constipation, and liver injury, renal insufficiency, renal failure and proteinuria; and rash, alopecia, dermatitis and photosensitivity. Nursing responsibilities: Administer captopril on an empty stomach, preferably 1 hour before meals for maximum effectiveness. Monitor the patient taking captopril for proteinuria every 2-4 weeks for the first 3 months of therapy to detect decreased renal function. Tell the patient to report light-headedness, especially in the first few days of starting therapy, so the dosage may be adjusted. Advise the patient to avoid sudden position changes to minimize orthostatic hypotension Encourage nonpharmacologic treatments for hypertension, such as sodium reduction, calorie reduction, stress management and exercise. Angiotensin II Receptor Blockers Actions and Indications: Angiotensin Receptor Blockers (ARBs) bind to angiotensin II receptors in blood vessels and the adrenal cortex. This action blocks vasoconstriction (narrowing the blood vessels) and aldosterone release, thus lowering blood pressure. ARBs are used to treat hypertension and heart failure in patients who cannot tolerate ACE inhibitors. Recent studies show they also slow the progression of kidney disease in patients with hypertension and type 2 diabetes. This effect is likely due to the blocking of angiotensin receptors in the blood vessel lining. Pharmacokinetics: These agents are administered orally, readily absorbed, metabolized in the liver and excreted through feces and urine. It can cross the placenta. However, it is currently unknown if they’re present in breastmilk. Angiotensin receptor blockers should not be used by people allergic to them to prevent hypersensitivity reactions. Caution is advised for those with liver or kidney problems, as ARBs can affect how the body processes and removes them. Also contraindicated during pregnancy due to risk of serious birth defects and death. It’s unknown if ARBs pass into breastmilk, they should not be used during breast feeding to avoid potential harm to the baby. Women of childbearing age should use contraception while taking ARBs, and the medication should be stopped immediately if pregnancy occurs. Adverse Effects: Common adverse effects include headache, dizziness, fainting, weakness, low blood pressure, digestive issues (diarrhea, abdominal pain and nausea), dry mouth tooth pain, respiratory infections, cough, rash, dry skin, and hair loss. In pre-clinical trials, ARBs have been linked to cancer and kidney damage. Regular monitoring of kidney function is recommended when using these drugs. Nursing Responsibilities: Alert the practitioner that patient is taking an ARB before surgery because of potential complications from blocking the renin-angiotensin system. Monitor the patient’s blood pressure carefully, additive therapy may be required if drug does not achieved desired levels Instruct the patient to maintain fluid intake, especially when in a situation that can result in excessive fluid loss, such as diarrhea, vomiting or excessive sweating.  Teach the patient ways to minimize orthostatic hypotension. Stress the importance of continuing with nonpharmacologic therapies such as diet modification, exercise and stress reduction. Calcium Channel Blockers Calcium channel blockers decrease BP, cardiac workload, and myocardial oxygen consumption. The effects of these drugs on cardiac workload also make them very effective in the treatment of angina. Actions and Indications: Inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction. These effect depresses myocardial contractility, slows cardiac impulse formation in the conductive tissues, relaxes and dilates arteries, causing a fall in BP and decrease in venous return. Pharmacokinetics: Calcium-channel blockers are given orally and are generally well absorbed, metabolized in the liver and excreted in the urine. These drugs cross the placenta and enter breastmilk. Nicardipine and Clevidipine are available in IV form for short-term use when oral administration is not feasible. Contraindications and Cautions: Should not be used by people with allergies to them, those with heart block or sick sinus syndrome, or those with kidney or liver problems. Not recommended during pregnancy unless the benefit to the mother clearly outweighs the risk to the fetus. Due to potential harm to the baby, alternative feeding methods should be used during breastfeeding if these drugs are necessary. Adverse Effects: The drugs have adverse effects related to their impact on the heart (cardiac output) and smooth muscles. These effects include: CNS: dizziness, lightheadedness, headache and fatigue GI: nausea and liver (hepatic) damage due to direct toxic effects on liver cells. CV: low blood pressure, slow heart rate, swelling in the extremities (peripheral edema), and heart block. Skin: flushing and rashes Nursing Responsibilities: > Know that nifedipine is given sublingual. The patient can puncture the capsule and squeeze the liquid under the tongue. Some institutions vary in this policy; the patient may be asked to swallow the capsule after sublingual dosing. > Withhold the dose and notify the practitioner if the patient’s systolic pressure is less than 90mmhg or the heart rate is less than 60 bpm. Monitor the patient for signs and symptoms of heart failure. Warn the patient not to stop the drug abruptly; gradually reducing the dosage under doctor’s supervision helps prevent rebound hypertension. Vasodilators If other drug therapies do not achieve the desired reduction in BP, it is sometimes necessary to use a direct vasodilator. Most of the vasodialtors are reserved for use in severe hypertension, malignant hypertension or hypertensive emergencies. Actions and Indications: Acts directly on vascular smooth muscle to cause muscle relaxation, leading to vasodilation and drop in BP. They do not block the reflex tachycardia that occurs when BP drops. They are indicated for the treatment of severe hypertension that has not responded to other therapy. Pharmacokinetics: Nitroprusside is used IV; Hydralazine is available for oral, IV and IM use; Minoxidil is available as an oral agent only. These drugs are rapidly absorbed and widely distributed. They are metabolized in the liver and primarily excreted in the urine. They cross the placenta and enter breastmilk. Contraindications and Cautions: Contraindicated in patients with known allergies and in those with conditions that could worsen with a sudden drop in blood pressure, such as cerebral insufficiency. Caution is advised for patients with peripheral vascular disease, CAD, heart failure or tachycardia. Also contraindicated during pregnancy. If used by a nursing mother, alternative feeding methods should be considered. Adverse Effects: the adverse effects most frequently seen with these drugs are related to the changes in BP. These include: Dizziness, Anxiety, Headache, Reflex tachycardia, Heart failure, Chest pain, Edema, Skin rashes, Lesions, GI upset, Nausea, and vomiting. Cyanide toxicity ( dyspnea, headache, vomiting, dizziness, ataxia, loss of consciousness, imperceptible pulse, absent reflexes, dilated pupils, pink color, distant heart sounds, and shallow breathing) may occur with nitroprusside, which is metabolized to cyanide and also suppresses iodine uptake and can cause hypothyroidism. OTHER ANTIHYPERTENSIVE AGENTS Diuretic Agents Diuretics are drugs that increase sodium and water excretion from the kidneys, making them a first-line treatment for mild hypertension. Studies show that less expensive, less toxic diuretics, particularly thiazide diuretics (like chlorothiazide, hydrochlorothiazide, methyclothiazide and chlorthalidone, indapamide and metolazone), are as effective as other antihypertensives and are well tolerated. Other diuretics include potassium-sparing options such as amiloride, spironolactone, and triamterene. While diuretics increase urination and can affect electrolyte balance, they are generally well tolerated.