PHARMA-NOTES-FINAL.pdf

PHARMA NOTES (SUMMARY) ***CARDIOVASCULAR SYSTEM*** ❖ The heart is a hollow muscle that is divided into a right and a left side by a thick septum and into four chambers—the two upper atria and the two lower ventricles. The right side of the heart receives all of the deoxygenated blood fro...

PHARMA NOTES (SUMMARY) ***CARDIOVASCULAR SYSTEM*** ❖ The heart is a hollow muscle that is divided into a right and a left side by a thick septum and into four chambers—the two upper atria and the two lower ventricles. The right side of the heart receives all of the deoxygenated blood from the body through the veins and directs it into the lungs. The left side of the heart receives oxygenated blood from the lungs and pumps it out to every cell in the body through the arteries. ❖ The heart is responsible for pumping oxygenated blood to every cell in the body and for picking up waste products from the tissues. ❖ The cardiac cycle consists of a period of rest, or diastole, when blood is returned to the heart by veins, and a period of contraction, or systole, when the blood is pumped out of the heart. ❖ The heart muscle possesses the properties of automaticity (the ability to generate an action potential in the absence of stimulation) and conductivity (the ability to rapidly transmit an action potential). ❖ The heart muscle is stimulated to contract by impulses generated in the heart, not by stimuli from the brain. The autonomic nervous system can affect the heart to increase (sympathetic) or decrease (parasympathetic) activity. ❖ In normal sinus rhythm, cells in the SA node generate an impulse that is transmitted through the atrial bundles and delayed slightly at the AV node before being sent down the bundle of His into the ventricles. When cardiac muscle cells are stimulated, they contract. ❖ Alterations in the generation of conduction of impulses in the heart cause arrhythmias (dysrhythmias), which can upset the normal balance in the cardiovascular system and lead to a decrease in cardiac output, affecting all of the cells of the body. ❖ Heart muscle contracts by the sliding of actin and myosin filaments in a functioning unit called a sarcomere. Contraction requires energy and calcium to allow the filaments to react with each other and slide together. ❖ The heart muscle needs a constant supply of blood, which is furnished by the coronary arteries. Increase in demand for oxygen can occur with changes in heart rate, preload, afterload, or stretch on the muscle. ❖ The cardiovascular system is a closed pressure system that uses arteries (muscular, pressure, or resistance vessels) to carry blood from the heart, veins (flexible, distensible capacitance vessels) to return blood to the heart, and capillaries (which connect arteries to veins) to keep blood flowing from areas of high pressure to areas of low pressure. ❖ Blood pressure is maintained by stimulus from the sympathetic system and reflex control of blood volume and pressure by the renin–angiotensin system and the aldosterone–ADH system. Alterations in blood pressure (hypotension or hypertension) can upset the balance of the cardiovascular system and lead to problems in blood delivery. ❖ Fluid shifts out of the blood at the arterial ends of capillaries to deliver oxygen and nutrients to the tissues. It moves out due to the hydrostatic or fluid pressure of the arterial side of the system. Fluid returns to the system at the venous end of the capillaries because of the oncotic pull of proteins in the vessels. Disruptions in these pressures can lead to edema or loss of fluid in the tissues. ANTIHYPERTENSIVE AGENTS ❖ The CV system is a closed system that depends on pressure differences to ensure the delivery of blood to the tissues and the return of that blood to the heart. ❖ BP is related to heart rate, stroke volume, and the total peripheral resistance against which the heart has to push the blood. ❖ Peripheral resistance is primarily controlled by constriction or relaxation of the arterioles. Constricted arterioles raise pressure; dilated arterioles lower pressure. ❖ Control of BP involves baroreceptor (pressure receptor) stimulation of the medulla to activate the sympathetic nervous system, which causes vasoconstriction and increased fluid retention when pressure is low in the aorta and carotid arteries, and vasodilation and loss of fluid when pressure is too high. ❖ The kidneys activate the renin–angiotensin–aldosterone system when blood flow to the kidneys is decreased. ❖ Renin activates the conversion of angiotensinogen to angiotensin I in the liver; angiotensin I is converted by ACE to angiotensin II in the lungs; angiotensin II then reacts with specific receptor sites on blood vessels to cause vasoconstriction to raise BP and in the adrenal gland to cause the release of aldosterone, which leads to the retention of fluid and increased blood volume. ❖ Hypertension is a sustained state of higher-than-normal BP that can lead to damage to blood vessels, increased risk of atherosclerosis, and damage to small vessels in end organs. Because hypertension often has no signs or symptoms, it is called the silent killer. ❖ Essential hypertension has no underlying cause, and treatment can vary widely from individual to individual. Treatment approaches include lifestyle changes first, followed by careful addition and adjustment of various antihypertensive drugs. ❖ Drug treatment of hypertension is aimed at altering one or more of the normal reflexes that control BP: Diuretics decrease sodium levels and volume, sympathetic nervous system drugs alter the sympathetic response and lead to vascular dilation and decreased pumping power of the heart, ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, ARBs prevent the body from responding to angiotensin II, renin inhibitors directly block the effects of renin, calcium-channel blockers interfere with the ability of muscles to contract and lead to vasodilation, and vasodilators directly cause the relaxation of vascular smooth muscle. ❖ Hypotension is a state of lower-than-normal BP that can result in decreased oxygenation of the tissues, cell death, tissue damage, and even death. ❖ Hypotension is most often treated with sympathomimetic drugs, which stimulate the sympathetic receptor sites to cause vasoconstriction, fluid retention, and return of normal pressure. ANTIARRHYTHMICS ❖ Disruptions in the normal rate or rhythm of the heart are called arrhythmias (also known as dysrhythmias). ❖ Electrolyte disturbances, decreases in the oxygen delivered to the cells leading to hypoxia or anoxia, structural damage that changes the conduction pathway, acidosis or the accumulation of waste products, or drug effects can lead to disruptions in the automaticity of the cells or in the conduction of the impulse that result in arrhythmias. The result can be changes in heart rate (tachycardias or bradycardias), stimulation from ectopic foci in the atria or ventricles that cause an uncoordinated muscle contraction, or blocks in the conduction system (e.g., AV heart block, bundle branch blocks) that alter the normal movement of the impulse through the system.  ❖ Arrhythmias cause problems because they alter the hemodynamics of the cardiovascular system. They can cause a decrease in cardiac output related to the uncoordinated pumping action of the irregular rhythm, leading to lack of filling time for the ventricles. Any of these effects can interfere with the delivery of blood to the brain, to other tissues, or to the heart muscle. ❖ Antiarrhythmics are drugs that alter the action potential of the heart cells and interrupt arrhythmias. The CAST study found that the long-term treatment of arrhythmias may actually cause cardiac death, so these drugs are now indicated only for the short-term treatment of potentially life-threatening ventricular arrhythmias. ❖ Class I antiarrhythmics block sodium channels, depress phase 0 of the action potential, and generally prolong the action potential, leading to a slowing of conduction and automaticity. ❖ Class II antiarrhythmics are beta-adrenergic receptor blockers that prevent sympathetic stimulation. ❖ Class III antiarrhythmics block potassium channels and prolong phase 3 of the action potential. ❖ Class IV antiarrhythmics are calcium-channel blockers that shorten the action potential, disrupting ineffective rhythms and rates. ❖ A patient receiving an antiarrhythmic drug needs to be constantly monitored while being stabilized and throughout the course of therapy to detect the development of arrhythmias or other adverse effects associated with alteration of the action potentials of other muscles or nerves. AGENTS FOR TREATING HEART FAILURE ❖ HF, a condition in which the heart muscle fails to effectively pump blood through the CV system, can be the result of a damaged heart muscle and increased demand to work harder. ❖ The sarcomere—the functioning unit of the heart muscle—is made up of protein fibers: Thin actin fibers and thick myosin fibers, which react with each other when calcium is present to inactivate troponin. The fibers slide together, resulting in contraction. Failing cardiac muscle cells lose the ability to effectively use energy to move calcium into the cell, and contractions become weak and ineffective. ❖ Cardiotonic (inotropic) agents are one class of drugs used in the treatment of HF. These agents directly stimulate the muscle to contract more effectively. ❖ Cardiac glycosides increase the movement of calcium into the heart muscle. This results in increased force of contraction, which increases blood flow to the kidneys (causing a diuretic effect), slows the heart rate, and slows conduction through the AV node. All of these effects decrease the heart’s workload. Digoxin is the cardiac glycoside most commonly used to treat HF. ❖ Phosphodiesterase inhibitors block the breakdown of cAMP in the cardiac muscle. This allows more calcium to enter the cell (leading to more intense contraction) and increases the effects of sympathetic stimulation (which can lead to vasodilation but also can increase pulse, blood pressure, and workload on the heart). Because these drugs are associated with severe effects, they are reserved for use in extreme situations. ❖ HCN blockers slow the repolarization of the heart’s pacemaker, leading to a slower heart rate. Slowing the heart rate allows more time for filling and improves cardiac output. This class of drugs does not affect ventricular cell activity. The systemic effects seen with the use of beta-blockers do not occur with this class of drugs. ❖ Disruptions in the normal rate or rhythm of the heart are called arrhythmias (also known as dysrhythmias). ❖ Electrolyte disturbances, decreases in the oxygen delivered to the cells leading to hypoxia or anoxia, structural damage that changes the conduction pathway, acidosis or the accumulation of waste products, or drug effects can lead to disruptions in the automaticity of the cells or in the conduction of the impulse that result in arrhythmias. The result can be changes in heart rate (tachycardias or bradycardias),  stimulation from ectopic foci in the atria or ventricles that cause an uncoordinated muscle contraction, or blocks in the conduction system (e.g., AV heart block, bundle branch blocks) that alter the normal movement of the impulse through the system. ❖ Arrhythmias cause problems because they alter the hemodynamics of the cardiovascular system. They can cause a decrease in cardiac output related to the uncoordinated pumping action of the irregular rhythm, leading to lack of filling time for the ventricles. Any of these effects can interfere with the delivery of blood to the brain, to other tissues, or to the heart muscle. ❖ Antiarrhythmics are drugs that alter the action potential of the heart cells and interrupt arrhythmias. The CAST study found that the long-term treatment of arrhythmias may actually cause cardiac death, so these drugs are now indicated only for the short-term treatment of potentially life-threatening ventricular arrhythmias. ❖ Class I antiarrhythmics block sodium channels, depress phase 0 of the action potential, and generally prolong the action potential, leading to a slowing of conduction and automaticity. ❖ Class II antiarrhythmics are beta-adrenergic receptor blockers that prevent sympathetic stimulation. ❖ Class III antiarrhythmics block potassium channels and prolong phase 3 of the action potential. ❖ Class IV antiarrhythmics are calcium-channel blockers that shorten the action potential, disrupting ineffective rhythms and rates. ❖ A patient receiving an antiarrhythmic drug needs to be constantly monitored while being stabilized and throughout the course of therapy to detect the development of arrhythmias or other adverse effects associated with alteration of the action potentials of other muscles or nerves. ANTIANGINAL AGENTS ❖ CAD, the leading cause of death in the United States and most Western nations, develops when changes in the intima of coronary vessels lead to the development of atheromas or fatty tumors, accumulation of platelets and debris, and a thickening of arterial muscles, resulting in a loss of elasticity and responsiveness to normal stimuli. ❖ Narrowing of the coronary arteries secondary to atheroma buildup is called atherosclerosis. ❖ Narrowed coronary arteries eventually become unable to deliver all the blood that is needed by the myocardial cells, causing a problem of supply and demand. ❖ Angina pectoris, or “suffocation of the chest,” occurs when the myocardial demand for oxygen cannot be met by the narrowed vessels. Pain, anxiety, and fatigue develop when the supply-and-demand ratio is upset. Types of angina include stable, unstable, and Prinzmetal angina. ❖ MI occurs when a coronary vessel is completely occluded and the cells that depend on that vessel for oxygen become ischemic, then necrotic, and die. ❖ Angina can be treated by drugs that either increase the supply of oxygen or decrease the heart’s workload, which decreases the demand for oxygen. ❖ Nitrates and beta-blockers are used to cause vasodilation and to decrease venous return and arterial resistance—effects that decrease cardiac workload and oxygen consumption. ❖ Nitroglycerin is the drug of choice for treating an acute anginal attack. It is available in various forms. ❖ Beta-blockers prevent the activation of sympathetic receptors, which normally would increase heart rate, increase blood pressure, and increase cardiac contraction. All of these actions would increase the demand for oxygen; blocking these actions decreases the demand for oxygen.  ❖ Calcium-channel blockers block muscle contraction in smooth muscle and decrease the heart’s workload, relax vasospasm in Prinzmetal angina, and possibly block the proliferation of the damaged endothelium in coronary vessels. ❖ The newest drug approved for the treatment of angina is the piperazine acetamide agent ranolazine. The mechanism of action of this drug is not understood. It prolongs QT intervals, does not slow heart rate or blood pressure, but decreases myocardial oxygen demand. LIPID-LOWERING AGENTS ❖ CAD is the leading cause of death in the Western world. It is associated with the development of atheromas or plaques in arterial linings that lead to narrowing of the lumen of the artery and hardening of the artery wall, with loss of distensibility and responsiveness to stimuli for contraction or dilation. ❖ The cause of CAD is not understood, but many contributing risk factors have been identified, including increasing age, male gender, genetic predisposition, high-fat diet, sedentary lifestyle, smoking, obesity, high stress levels, bacterial infections, diabetes, hypertension, gout, and menopause. The presence of many of these factors constitutes metabolic syndrome. ❖ Treatment and prevention of CAD is aimed at manipulating the known risk factors to decrease CAD development and progression. ❖ Fats are metabolized with the aid of bile acids, which act as a detergent to break fats into small molecules called micelles. Micelles are absorbed into the intestinal wall and combined with proteins to become chylomicrons, which can be transported throughout the circulatory system. ❖ Some fats are used immediately for energy or are stored in adipose tissue; others are processed in the liver to LDLs, which are associated with the development of CAD. LDLs are broken down in the periphery and leave many remnants (e.g., fats) that must be removed from blood vessels. This process involves the inflammatory reaction and may initiate or contribute to atheroma production. ❖ Some fats are processed into HDLs, which are able to absorb fats and remnants from the periphery and offer a protective effect against the development of CAD. ❖ Cholesterol is an important fat that is used to make bile acids. It is the base for steroid hormones and provides the necessary structure for cell membranes. All cells can produce cholesterol. ❖ HMG–CoA reductase is an enzyme that controls the final step in the production of cellular cholesterol. ❖ Patients taking lipid-lowering drugs need to include diet, exercise, and lifestyle changes to reduce the risk of CAD. ❖ Bile acid sequestrants bind with bile acids in the intestine and lead to their excretion in feces. This results in lower bile acid levels as the liver uses cholesterol to produce more bile acids. The end result is a decrease in serum cholesterol and LDL levels as the liver changes its metabolism of these fats to meet the need for more bile acids. ❖ HMG–CoA reductase inhibitors, or statins, block the enzyme HMG–CoA reductase, resulting in lower serum cholesterol levels, a resultant breakdown of LDLs, and a slight increase in HDLs. ❖ The cholesterol absorption inhibitor ezetimibe works in the brush border of the small intestine to prevent the absorption of dietary cholesterol, which leads to increased clearance of cholesterol by the liver and a resultant fall in serum cholesterol. ❖ Other agents used to lower cholesterol include fibrates, niacin, and omega-3 fatty acids. Often lipid-lowering agents are used in combination to lower the cholesterol at different sites.  ❖ Research is being done on the effects of blocking the endocannabinoid system, resulting in weight loss, improved lipid profiles, and decreased proinflammatory and prothrombotic states. Questions have not been answered about the safety or effectiveness of drugs that block this system. ANTICOAGULANTS ❖ Coagulation is the transformation of fluid blood into a solid state to plug up breaks in the vascular system. ❖ Coagulation involves several processes, including vasoconstriction, platelet aggregation to form a plug, and intrinsic and extrinsic clot formation initiated by the Hageman factor to plug any breaks in the system. ❖ The final step of clot formation is the conversion of prothrombin to thrombin, which breaks down fibrinogen to form insoluble fibrin threads. ❖ Once a clot is formed, it must be dissolved to prevent the occlusion of blood vessels and loss of blood supply to tissues. ❖ Plasminogen is the basis of the clot-dissolving system. It is converted to plasmin (fibrinolysin) by several factors, including the Hageman factor. Plasmin dissolves fibrin threads and resolves the clot. ❖ Anticoagulants block blood coagulation by interfering with one or more of the steps involved, such as blocking platelet aggregation or inhibiting the intrinsic or extrinsic pathways to clot formation. ❖ Thrombolytic drugs dissolve clots or thrombi that have formed. They activate the plasminogen system to stimulate natural clot dissolution. ❖ Hemostatic drugs are used to stop bleeding. They may replace missing clotting factors or prevent the plasminogen system from dissolving formed clots. ❖ Hemophilia, a genetic lack of essential clotting factors, results in excessive bleeding. It is treated by replacing missing clotting factors. DRUGS USED TO TREAT ANEMIAS ❖ Blood is composed of liquid plasma and formed elements (white blood cells, RBCs, and platelets) and contains oxygen and nutrients that are essential for cell survival; it delivers these to the cells and removes waste products from the tissues. ❖ RBCs are produced in the bone marrow in a process called erythropoiesis, which is controlled by the glycoprotein erythropoietin, produced by the kidneys. ❖ RBCs do not have a nucleus, and their lifespan is about 120 days, at which time they are lysed and their building blocks are recycled to make new RBCs. ❖ The bone marrow uses iron, amino acids, carbohydrates, folic acid, and vitamin B12 to produce healthy, efficient RBCs. ❖ An insufficient number or immaturity of RBCs results in low oxygen levels in the tissues, with tiredness, fatigue, and loss of reserve. ❖ Anemia is a state of too few RBCs or ineffective RBCs. Anemia can be caused by a lack of erythropoietin or by a lack of the components needed to produce RBCs. ❖ Iron deficiency anemia occurs when there is inadequate iron intake in the diet or an inability to absorb iron from the GI tract. Iron is needed to produce hemoglobin, which carries oxygen. Iron deficiency anemia is treated with iron replacement. ❖ Iron is a very toxic mineral at high levels. The body controls the absorption of iron and carefully regulates its storage and movement in the body. ❖ Folic acid and vitamin B12 are needed to produce a strong supporting structure in  ❖ the RBC so that it can survive 120 days of being propelled through the vascular system. These are usually found in adequate amounts in the diet. Deficiencies are treated with folic acid and vitamin B12 replacement. ❖ A dietary lack of or inability to absorb folic acid, vitamin B12, or both will ❖ produce a megaloblastic anemia, in which the RBCs are large and immature and have a short lifespan. ❖ Pernicious anemia is a lack of vitamin B12, which is also used by the body to maintain the myelin sheath on nerve axons. If vitamin B12 is lacking, these neurons will degenerate and cause many CNS effects. ❖ Pernicious anemia is caused by the deficient production of intrinsic factor by gastric cells. ❖ Intrinsic factor is needed to allow the body to absorb vitamin B12. If intrinsic factor is lacking, vitamin B12 must be given parenterally or intranasally for life to ensure absorption. ❖ Sickle cell anemia is a genetic disorder characterized by the production of hemoglobin S. The RBCs have a sickle shape and can stack up in blood vessels and cause anoxia, pain, and even cell death. ❖ Sickle cell anemia is treated with antibiotics, pain-relieving measures, and the cytotoxic drug hydroxyurea, which causes increased fetal hemoglobin production in the bone marrow and dilution of hemoglobin S with a resultant reduction in RBC stacking and clogging of blood vessels. ***RENAL SYSTEM*** The kidneys are two small, bean-shaped organs that receive about 25% of the cardiac output. The nephron is the functional unit of the kidneys and is involved in three processes: Glomerular filtration, tubular secretion, and tubular reabsorption. The kidney plays a key role in regulating body fluid volume and maintaining blood pressure, red blood cell production, acid–base balance, and electrolyte stability. The renin–angiotensin–aldosterone system is activated when blood flow to the nephron is decreased and renin is released. The end result is increased vasoconstriction and increased blood pressure and sodium and water retention, which increase blood volume and pressure. Red blood cell production is controlled by erythropoietin released from the juxtaglomerular apparatus when oxygen delivery to the nephron is decreased. Erythropoietin stimulates the bone marrow to produce red blood cells to increase oxygen delivery to the nephrons. The functional unit of the kidneys is called the nephron; it is composed of Bowman’s capsule, the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct. The blood flow to the nephron is unique, allowing autoregulation of blood flow through the glomerulus. Sodium levels are regulated throughout the tubule by active and passive movement and are fine-tuned by the presence of aldosterone in the distal tubule. The countercurrent mechanism in the medullary nephrons allows for the concentration or dilution of urine under the influence of ADH secreted by the hypothalamus. Potassium concentration is regulated throughout the tubule, with aldosterone being the strongest influence for potassium loss. The kidneys play a key role in the regulation of calcium by activating vitamin D to allow GI calcium reabsorption and by reabsorbing or excreting calcium from the tubule under the influence of PTH.  The kidneys influence blood pressure control, releasing renin to activate the renin–angiotensin system, which leads to increased blood pressure and volume and a resultant increased blood flow to the kidney. The balance of this reflex system can lead to water retention or excretion and has an impact on drug therapy that promotes water or sodium loss. The ureters, urinary bladder, and urethra make up the rest of the urinary tract. The longer male urethra passes through the prostate gland, which may enlarge or become infected, a problem often associated with advancing age. DIURETIC AGENTS Diuretics—drugs that increase the excretion of sodium, and therefore water, from the kidneys—are used in the treatment of edema associated with HF and pulmonary edema, liver failure and cirrhosis, and various types of renal disease, and as adjuncts in the treatment of hypertension. Classes of diuretics differ in their site of action and intensity of effects. Thiazide diuretics work to block the chloride pump in the distal convoluted tubule. This effect leads to a loss of sodium and potassium and a minor loss of water. Thiazides are frequently used alone or in combination with other drugs to treat hypertension. They are considered to be mild diuretics. Loop diuretics work in the loop of Henle and have a powerful diuretic effect, leading to the loss of water, sodium, and potassium. These drugs are the most potent diuretics and are used in acute situations, as well as in chronic conditions not responsive to milder diuretics. Carbonic anhydrase inhibitors work to block the formation of carbonic acid and bicarbonate in the renal tubule. These drugs can cause an alkaline urine and loss of the bicarbonate buffer. Carbonic anhydrase inhibitors are used in combination with other diuretics when a stronger diuresis is needed, and they are frequently used to treat glaucoma because they decrease the amount of aqueous humor produced in the eye. Potassium-sparing diuretics are mild diuretics that act to spare potassium in exchange for the loss of sodium and water in the urine. These diuretics are preferable if potassium loss could be detrimental to a patient’s cardiac or neuromuscular condition. Patients must be careful not to become hyperkalemic while taking these drugs. The osmotic diuretic mannitol uses hypertonic pull to remove fluid from the intravascular spaces and to deliver large amounts of water into the renal tubule. There is a danger of sudden change of fluid volume and massive fluid loss with this drug. This drug is used to decrease intracranial pressure, to treat glaucoma, and to help push toxic substances through the kidneys. DRUGS AFFECTING THE URINARY TRACT AND THE BLADDER Urinary tract anti-infectives include two groups of drugs: Antibiotics that are particularly effective against gram-negative bacteria, and drugs that work to acidify the urine, ultimately killing the bacteria that might be in the bladder. Many activities are necessary to help decrease the bacteria in the urinary tract (e.g., hygiene measures, proper diet, forcing fluids) to facilitate the treatment of UTIs and help the urinary tract anti-infectives be more effective. Inflammation and irritation of the urinary tract can cause smooth muscle spasms along the urinary tract. These spasms lead to the uncomfortable effects of dysuria, urgency, incontinence, nocturia, and suprapubic pain. The urinary tract antispasmodics act to relieve spasms of the urinary tract muscles by blocking parasympathetic activity and relaxing the detrusor and other urinary tract muscles.  The urinary tract analgesic phenazopyridine is used to provide relief of symptoms (burning, urgency, frequency, pain, discomfort) related to urinary tract irritation resulting from infection, trauma, or surgery. Pentosan polysulfate sodium is a heparin-like compound that has anticoagulant and fibrinolytic effects and adheres to the bladder wall mucosal membrane to act as a buffer to control cell permeability. This action prevents irritating solutes in the urine from reaching the cells of the bladder wall. It is used specifically to decrease the pain and discomfort associated with interstitial cystitis. BPH is a common enlargement of the prostate gland in older men. Drugs frequently used to relieve the signs and symptoms of prostate enlargement include alpha-adrenergic blockers, which relax the sympathetic effects on the bladder and sphincters, and finasteride and dutasteride, which block the body’s production of a powerful androgen. The prostate is dependent on testosterone for its maintenance and development; blocking the androgen leads to shrinkage of the gland and relief of symptoms. ***RESPIRATORY SYSTEM*** The respiratory system has two parts: The upper respiratory tract, which includes the nose, pharynx, larynx, and trachea, and the lower respiratory tract, which includes the bronchial tree and alveoli. Gas exchanges occur in the alveoli. Nasal hairs, mucus-producing goblet cells, cilia, the superficial blood supply of the upper respiratory tract, and the cough and sneeze reflexes all work to keep foreign substances from entering the lower respiratory tract. Gas exchange occurs across the respiratory membrane in the alveolar sac. The type 2 cells of the alveoli produce surfactant, which reduces surface tension to keep the alveoli open for gas exchange. The medulla controls respiration, which depends on a functioning muscular system and a balance between the sympathetic and parasympathetic systems. The respiratory system is composed of the upper respiratory tract, which includes the nose, pharynx, larynx, and trachea, and the lower respiratory tract, which includes the bronchial tree and the alveoli. The respiratory system is essential for survival; it brings oxygen into the body, allows for the exchange of gasses, and expels carbon dioxide and other waste products. The upper airways have many features to protect the fragile alveoli: Hairs filter the air; goblet cells produce mucus to trap foreign material; cilia move the trapped material toward the throat for swallowing; the blood supply close to the surface warms the air and adds humidity to improve gas movement and gas exchange; and the cough and sneeze reflexes clear the airways. The alveolar sac is where gas exchange occurs across the respiratory membrane. The alveoli produce surfactant to decrease surface tension within the sac and facilitate diffusion. Respiration is controlled through the medulla in the central nervous system and depends on a balance between the sympathetic and parasympathetic systems and a functioning muscular system. Inflammation of the upper respiratory tract is seen in many disorders, including the common cold, seasonal rhinitis, sinusitis, pharyngitis, and laryngitis. Inflammation of the lower respiratory tract can result in serious disorders that interfere with gas exchange, including bronchitis and pneumonia.  Obstructive disorders interfere with the ability to deliver gasses to the alveoli because of obstructions in the conducting airways and eventually in the respiratory airways. These disorders include asthma, COPD, CF, and RDS. DRUGS ACTING ON THE UPPER RESPIRATORY TRACT The classes of drugs that affect the upper respiratory system work to keep the airways open and gasses moving efficiently. Antitussives are drugs that suppress the cough reflex. They can act centrally to suppress the medullary cough center or locally to increase secretion and buffer irritation or to act as local anesthetics. These drugs should not be used longer than 1 week; patients with persistent cough after that time should seek medical evaluation. Decongestants are drugs that cause local vasoconstriction and therefore decrease the blood flow to the irritated and dilated capillaries of the mucous membranes lining the nasal passages and sinus cavities. An adverse effect that accompanies frequent or prolonged use of decongestants is rebound vasodilation, called rhinitis medicamentosa. The reflex reaction to vasoconstriction is a rebound vasodilation, which often leads to prolonged overuse of decongestants. Topical nasal decongestants are preferable in patients who need to avoid systemic adrenergic effects. Oral decongestants are associated with systemic adrenergic effects and require caution in patients with CV disease, hyperthyroidism, or diabetes mellitus. Topical nasal steroid decongestants block the inflammatory response from occurring. These drugs, which take several days to weeks to reach complete effectiveness, are preferred for patients with allergic rhinitis who need to avoid the complications of systemic steroid therapy. The antihistamines selectively block the effects of histamine at the histamine-1 receptor sites, decreasing the allergic response. Antihistamines are used for the relief of symptoms associated with seasonal and perennial allergic rhinitis, allergic conjunctivitis, uncomplicated urticaria, or angioedema. Patients taking antihistamines may react to dryness of the skin and mucous membranes. The nurse should encourage them to drink plenty of fluids, use a humidifier if possible, avoid smoke-filled rooms, and use good skin care and moisturizers. Antihistamines should be avoided with any patient who has a prolonged QT interval because serious cardiac complications and even death have occurred. Expectorants are drugs that liquefy lower respiratory tract secretions. They are used for the symptomatic relief of respiratory conditions characterized by a dry, nonproductive cough. Mucolytics work to break down mucus to aid high-risk respiratory patients in coughing up thick, tenacious secretions. Many of the drugs that act on the upper respiratory tract are found in various OTC cough and allergy preparations. Patients need to be advised to always read the labels carefully to avoid inadvertent overdose and toxicity. DRUGS ACTING ON THE LOWER RESPIRATORY TRACT Pulmonary obstructive diseases include asthma and COPD, which includes emphysema and chronic bronchitis—these disorders cause obstruction of the major airways—and RDS, which causes obstruction at the alveolar level. Drugs used to treat asthma and COPD include drugs to block inflammation and drugs to dilate bronchi.  The xanthine derivatives have a direct effect on the smooth muscle of the respiratory tract, both in the bronchi and in the blood vessels. The adverse effects of the xanthines are directly related to the theophylline concentration in the blood and can progress to coma and death. Sympathomimetics are drugs that mimic the effects of the sympathetic nervous system; they are used for dilation of the bronchi and to increase the rate and depth of respiration. Anticholinergics can be used as bronchodilators because of their effect on the vagus nerve, resulting in relaxation of smooth muscle in the bronchi, which leads to bronchodilation. Steroids are used to decrease the inflammatory response in the airway. Inhaling the steroid tends to decrease the numerous systemic effects that are associated with steroid use. Leukotriene receptor antagonists block or antagonize receptors for the production of leukotrienes D4 and E4, thus blocking many of the signs and symptoms of asthma. Lung surfactants are instilled into the respiratory system of premature infants who do not have enough surfactant to ensure alveolar expansion. ***GASTROINTESTINAL SYSTEM*** ➔ The GI system begins at the mouth and ends at the anus; a long tube extends between them and comprises the esophagus, the stomach, the small intestine, and the large intestine. Essential functions are digestion and absorption of nutrients. The GI tract is composed of four layers: The mucosa, the muscularis mucosa, the nerve plexus, and the adventitia. ➔ The GI tract has four major functions: Secretion, absorption, digestion, and motility. The GI system secretes enzymes, acid, bicarbonate, and mucus to facilitate the digestion and absorption of nutrients. The small intestine is the section of the GI tract where most absorption occurs. The veins of the small intestine carry the absorbed products to the liver for filtering, cleaning, and metabolism, or the breaking down of absorbed products into usable substances. ➔ The nerve plexus controls the GI system by maintaining electrical rhythm and responding to local stimuli (increasing or decreasing activity). The autonomic nervous system influences GI activity, with the sympathetic system slowing and the parasympathetic system increasing activity. ➔ The GI system is composed of one long tube that starts at the mouth, includes the esophagus, the stomach, the small intestine, and the large intestine, and ends at the anus. The GI system is responsible for digestion and absorption of nutrients. ➔ Secretion of digestive enzymes, acid, bicarbonate, and mucus facilitates the digestion and absorption of nutrients. ➔ The GI system is controlled by a nerve plexus, which maintains a BER and responds to local stimuli to increase or decrease activity. The sympathetic nervous system, if stimulated, slows GI activity; stimulation of the parasympathetic nervous system increases activity. Initiation of activity depends on local reflexes. ➔ A series of local reflexes within the GI tract helps to maintain homeostasis within the system. Overstimulation of any of these reflexes can result in constipation (underactivity) or diarrhea (overactivity). ➔ Swallowing, a centrally mediated reflex important in delivering food to the GI tract for processing, is controlled by the medulla. It involves a complex series of timed reflexes.  ➔ Vomiting is controlled by the CTZ in the medulla or by the emetic zone in immature or injured brains. The CTZ is stimulated by several different processes and initiates a complex series of responses that first prepare the system for vomiting and then cause a strong backward peristalsis to rid the stomach of its contents. DRUGS AFFECTING GI SECRETIONS ➔ GI complaints are some of the most common symptoms seen in clinical practice. ➔ Peptic ulcers may result from increased acid production, decrease in the protective mucous lining of the stomach, infection with Helicobacter pylori bacteria, or a combination of these. ➔ Agents used to decrease the acid content of the stomach include H2 antagonists, ➔ which block the release of acid in response to gastrin or parasympathetic release; antacids, which chemically react with the acid to neutralize it; proton pump inhibitors, which block the last step of acid production to prevent release; and prostaglandins, which block gastric acid secretion and increase bicarbonate production. ➔ Acid rebound occurs when the stomach produces more gastrin and more acid in response to lowered acid levels in the stomach, which commonly occurs with the use of antacids. Balancing the reduction of the stomach acid without increasing acid production is a clinical challenge. ➔ The GI protectant sucralfate forms a protective coating over the eroded stomach lining to protect it from acid and digestive enzymes to aid healing. ➔ The prostaglandin misoprostol blocks gastric acid secretion while increasing the production of bicarbonate and mucous lining in the stomach. ➔ Digestive enzymes such as substitute saliva and pancreatic enzymes may be needed if normal enzyme levels are very low and proper digestion cannot take place DRUGS AFFECTING GI MOTILITY ➔ Laxatives are drugs used to stimulate movement along the GI tract and to aid bowel evacuation. They may be used to prevent or treat constipation. ➔ Laxatives can be chemical stimulants, which directly irritate the local nerve plexus; bulk stimulants, which increase the size of the food bolus and stimulate stretch receptors in the wall of the intestine; or lubricants, which facilitate movement of the bolus through the intestines. ➔ Using proper diet and exercise, as well as taking advantage of the actions of the intestinal reflexes, has eliminated the need for laxatives in many situations. ➔ Cathartic dependence can occur with the chronic use of laxatives, leading to a need for external stimuli for normal functioning of the GI tract. ➔ GI stimulants act to increase parasympathetic stimulation in the GI tract and to increase tone and general movement throughout the GI system. ➔ Antidiarrheal drugs are used to soothe irritation to the intestinal wall, block GI muscle activity to decrease movement, or affect CNS activity to cause GI spasm and stop movement. ➔ Drugs used to treat IBS are specific for the main underlying complaint, either diarrhea or constipation, and patient selection must be carefully matched to the effect of the drug. ANTIEMETIC AGENTS ➔ Antiemetics are used to manage nausea and vomiting in situations in which these actions are not beneficial and could cause harm to the patient. Antiemetics act by depressing the hyperactive vomiting reflex, either locally or through alteration of CNS actions. ➔ The choice of an antiemetic depends on the cause of the nausea and vomiting and the expected actions of the drug. Antiemetics include the phenothiazines and centrally acting non phenothiazine metoclopramide, anticholinergic/antihistamines, the 5-HT3 receptor blockers, and ➔ the newest class of antiemetic, the substance P/NK1 antagonist. Other drugs used as antiemetics include cannabinoids, hydroxyzine, and trimethobenzamide. ➔ Phenothiazines and the non phenothiazine metoclopramide are used as antiemetics to depress the CNS, including the CTZ. Patients must be monitored for CNS depression. Photosensitivity and pink to red–brown color of the urine are common adverse effects of these drugs. ➔ The 5-HT3 blockers are newer antiemetics that directly block specific receptors in ➔ the CTZ to prevent nausea and vomiting. They are used in cases of nausea and vomiting associated with antineoplastic chemotherapy and radiation therapy and postoperative nausea and vomiting. ➔ Most antiemetics cause some CNS depression, with resultant dizziness, drowsiness, and weakness. Care must be taken to protect the patient and advise him or her to avoid dangerous situations. ➔ Photosensitivity is another common adverse effect with antiemetics. Patients should be protected from exposure to the sun and ultraviolet light. Sunscreens and protective clothing are essential if exposure cannot be prevented. ***REPRODUCTIVE SYSTEM*** ❖ The female ovary stores ova and produces the sex hormones estrogen and progesterone. The hypothalamus releases GnRH at puberty to stimulate the anterior pituitary release of FSH and LH, thus stimulating the production and release of the sex hormones. Levels are controlled by a series of negative feedback systems. ❖ Female sex hormones prepare the body for pregnancy and the maintenance of the pregnancy. If pregnancy does not occur the prepared inner lining of the uterus sloughs off as menstruation in the menstrual cycle. Menopause occurs when the supply of ova is exhausted and the woman’s body no longer produces the hormones estrogen and progesterone. ❖ The testes produce sperm in the seminiferous tubules in response to FSH stimulation and testosterone in the interstitial cells in response to LH stimulation. Testosterone is responsible for the development of male sex characteristics. These characteristics can be maintained by the androgens from the adrenal gland once the body has undergone the changes of puberty. ❖ Andropause or male climacteric, analogous to female menopause, occurs with age when the production of testosterone declines, with the subsequent loss of testosterone effects. ❖ The human sexual response involves activation of the sympathetic nervous system to allow a four-phase response: Stimulation, plateau, climax, and resolution.  Sexual stimulation and activity are a normal response and, in healthy individuals, are probably necessary for complete health of the body’s systems. ❖ Since activation of the sympathetic response is an integral part of the human sexual response, any disease process or drug therapy that interferes with the sympathetic response will alter the patient’s ability to experience a sexual response. ❖ Male and female reproductive systems arise from the same fetal cells. The female ovaries store ova and produce the sex hormones estrogen and progesterone; the male testes produce sperm and the sex hormone testosterone. ❖ The hypothalamus releases GnRH at puberty to stimulate the anterior pituitary release of FSH and LH, thus stimulating the production and release of the sex hormones. Levels are controlled by a series of negative feedback systems. ❖ Female sex hormones are released in a cyclical fashion. Release of an ovum for possible fertilization is termed ovulation. The female hormones prepare the body for pregnancy, including maintenance of the pregnancy if fertilization occurs. ❖ If pregnancy does not occur the prepared inner lining of the uterus is sloughed off as menstruation in the menstrual cycle, so that the lining can be prepared again when ovulation reoccurs. ❖ Menopause in women and the male climacteric in men occur when the body no longer produces sex hormones; the hypothalamus and anterior pituitary respond by releasing increasing levels of GnRH, FSH, and LH in an attempt to achieve higher levels of sex hormones. ❖ The testes produce sperm in the seminiferous tubules in response to FSH stimulation and testosterone in the interstitial cells in response to LH stimulation. ❖ Testosterone is responsible for the development of male sex characteristics. These characteristics can be maintained by the androgens from the adrenal gland once the body has undergone the changes of puberty. ❖ The human sexual response involves activation of the sympathetic nervous system to allow a four-phase response: Stimulation, plateau, climax, and resolution. DRUGS AFFECTING THE FEMALE REPRODUCTIVE SYSTEM ❖ Estrogens are hormones associated with the development of the female reproductive system and secondary sex characteristics; pharmacologically, estrogens are used to prevent conception, to stimulate ovulation in women with hypogonadism, and to a lesser extent to replace hormones after menopause. ❖ Progestins maintain pregnancy and are also involved with development of secondary sex characteristics. Progestins are used as part of combination contraceptives, to treat amenorrhea and functional uterine bleeding, and as part of fertility programs. Estrogen receptor modulators are used to stimulate specific estrogen receptors to achieve therapeutic effects of increased bone mass without stimulating the endometrium and causing other, less desirable estrogen effects. ❖ In women with functioning ovaries, fertility drugs increase follicle development by stimulating FSH and LH to increase the chances for pregnancy. Women receiving fertility drugs need to be monitored for ovarian overstimulation, need to be aware of the possibility of multiple births, and need support and encouragement to deal with the self-esteem issues associated with infertility. ❖ Oxytocic drugs act like the hypothalamic hormone oxytocin to stimulate uterine contractions and induce or speed up labor and to control bleeding and promote postpartum involution of the uterus.  Abortifacients are drugs that stimulate uterine activity to cause uterine evacuation. These drugs can be used to induce abortion in early pregnancy or to promote uterine evacuation after intrauterine fetal death. ❖ Tocolytics are drugs that relax the uterine smooth muscle; they are used to stop premature labor in patients after 20 weeks of gestation. Hydroxyprogesterone caproate is the only drug available for this purpose. ❖ Estrogens primarily are used pharmacologically to replace hormones lost at menopause to reduce the signs and symptoms associated with menopause, to stimulate ovulation in woman with hypogonadism, and in combination with progestins for oral contraceptives. ❖ Progestins, which include progesterone and all of its derivatives, are female sex hormones that are responsible for the maintenance of a pregnancy and for the development of some secondary sex characteristics. ❖ Progestins are used in combination with estrogens for contraception, to treat uterine bleeding, and for palliation in certain cancers with sensitive receptor sites. ❖ Fertility drugs stimulate FSH and LH in women with functioning ovaries to increase follicle development and improve the chances for pregnancy. ❖ A major adverse effect of fertility drugs is multiple births and birth defects. ❖ Oxytocic drugs act like the hypothalamic hormone oxytocin to stimulate uterine contractions and induce or speed up labor and to control bleeding and promote postpartum involution of the uterus. ❖ Abortifacients are drugs that stimulate uterine activity to cause uterine evacuation. These drugs can be used to induce abortion in early pregnancy or to promote uterine evacuation after intrauterine fetal death. ❖ Tocolytics are drugs that relax the uterine smooth muscle; they are used to stop premature labor in patients after 20 weeks of gestation. Hydroxyprogesterone caproate is the only drug approved for this purpose in the United States. DRUGS AFFECTING THE MALE REPRODUCTIVE SYSTEM ❖ Androgens are the male sex hormones that are responsible for the development and maintenance of male sex characteristics and secondary sex characteristics or androgenic effects. Androgens are used for replacement therapy or to block other hormonal effects. ❖ Anabolic steroids are testosterone analogues with more anabolic or protein-building effects than androgenic effects. Deadly effects may result from the abuse of anabolic steroids by athletes trying to build muscle mass and improve performance. ❖ Penile erectile dysfunction can inhibit erection and male sexual function. Alprostadil, a prostaglandin, can be injected into the penis to stimulate erection. The PDE5 inhibitors are oral agents that act quickly to promote vascular filling of the corpus cavernosum and promote penile erection. They differ in duration and time of onset. They are effective only in the presence of sexual stimulation. ❖ Androgens are male sex hormones—specifically testosterone or testosterone-like compounds. ❖ Androgens are responsible for the development and maintenance of male sex characteristics and secondary sex characteristics or androgenic effects. ❖ Side effects related to androgen use involve excess of the desired effects as well as potentially deadly hepatocellular carcinoma. ❖ Androgens can be used for replacement therapy or to block other hormone effects, as is seen with their use in the treatment of specific breast cancers. ❖ Anabolic steroids are analogues of testosterone that have been developed to have more anabolic or protein-building effects and fewer androgenic effects. ❖ Anabolic steroids have been abused to enhance muscle development and athletic performance, often with deadly effects. ❖ Anabolic steroids are used to increase hematocrit and improve protein anabolism in certain depleted states. ❖ Penile erectile dysfunction can inhibit erection and male sexual function. ❖ Alprostadil, a prostaglandin, can be injected into the penis to stimulate erection. ❖ The PDE5 inhibitors are oral agents that act quickly to promote vascular filling of the corpus cavernosum and promote penile erection. They differ in duration and time of onset. They are effective only in the presence of sexual stimulation. They are also used in the treatment of pulmonary arterial hypertension. ❖ Dangerous cardiovascular effects, including death, have occurred when the PDE5 inhibitors are combined with organic nitrates or alpha-blockers. Careful patient teaching is very important to avoid this drug–drug interaction.