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Drugs used to treat erectile dysfunction (1) Drugs in this class include sildenafil citrate (Viagra kamagra 100mg free shipping, Revatio) kamagra 100 mg overnight delivery, tadalafil (Cialis) cheap kamagra 50mg with mastercard, and var- denafil hydrochloride (Levitra) kamagra 100mg lowest price. Chapter 4 Drugs Acting on the Cardiovascular System 91 (2) Viagra was originally developed as an antianginal and antihypertensive agent but proved very effective in treating erectile dysfunction. The most serious adverse effects are cardiovascular: arrhythmias, heart block, cardiac arrest, stroke, and hypotension. Dietary or pharmacologic reduction of elevated plasma cholesterol levels can reduce the risk of atherosclerosis and subsequent cardiovascular disease. The exact factors linking elevated cho- lesterol levels to heart disease are not yet known. The association between cardiovascular disease and elevated plasma triglycerides is less dra- matic, but it is becoming more recognized. Cholesterol is a nonpolar, poorly water-soluble substance, transported in the plasma in par- ticles that have a hydrophobic core of cholesteryl esters and triglycerides surrounded by a coat of phospholipids, free cholesterol (nonesterified), and one or more apoproteins. Diseases of plasma lipids can be manifest as an elevation in triglycerides or as an elevation in cholesterol. In several of the complex or combined hyperlipoproteinemias, both triglyc- erides and cholesterol can be elevated. These drugs include lovastatin (mevinolin) (Mevacor), simvastatin (Zocor), pravastatin (Pravachol), and fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Inhibitors of cholesterol biosynthesis are effective in reducing choles- terol levels in familial and nonfamilial hypercholesterolemias. These drugs may also interfere with in- tracellular localization of certain oncogenes and thereby reduce the incidence of some cancers. Mechanism (1) Nicotinic acid can exert cholesterol- and triglyceride-lowering effects at high concentra- tions (nicotinamide cannot do this). Adverse effects (1) Nicotinic acid commonly produces flushing and an itching or burning feeling in the skin, which may reduce compliance. This is mediated by prostaglandin and histamine release and can be diminished by taking aspirin 30 minutes before taking nicotinic acid. Gemfibrozil (Lopid) (1) Gemfibrozil is a fibrate that is more effective than fenofibrate in some circumstances and has some unique biologic activities. Cholesterol is absorbed from the small intestine by a process that includes specific transporters that have not been completely characterized. Ezetimibe appears to block one or more of these choles- terol transporters, reducing cholesterol absorption. Ezetimibe used alone produces a reduction in plasma cholesterol of about 18% and about a 10% decline in triglyceride levels. When combined with a statin, reductions in plasma cho- lesterol as high as 72% have been reported in clinical trials. Ezetimibe appears to be well tolerated, with the most common adverse effects being fatigue, abdominal pain, and diarrhea. These agents include cholestyramine (Questran), colestipol (Colestid), and colesevelam (WelChol) a. Structure and mechanism (1) Bile acid sequestrants are large copolymers (resins) of hydrocarbons that can bind bile salts. Adverse effects (1) These agents are generally quite safe, because they are not absorbed in the intestine. A patient with a long history of cardiovascu- (D) Nifedipine lar disease develops worsening ventricular (E) Propranolol arrhythmias. A 16-year-old boy is brought to the hospital (A) Quinidine by ambulance following a car accident causing (B) Propanolol serious head injuries. Funduscopy reveals retinal dam- (D) Methyldopa age, and you administer nitroprusside via infusion. A patient is admitted into the emergency 72 hours and you notice the patient becoming room and manifests ventricular tachycardia fol- increasingly fatigued and nauseous. Which of the following nitroprusside drugs would be best to quickly control the (B) Negative inotropic activity of nitroprusside condition? His past medical work-up to diagnose the cause of a large multi- history includes a recent myocardial infarction nodular goiter develops atrial fibrillation. You decide that a medication side effect is the most likely cause of this (A) Verapamil patient’s symptoms. A 57-year-old man with atrial flutter is ini- (D) Digoxin tially treated with quinidine to control the ar- (E) Quinidine rhythmia. He is released from the hospital, and while his condition improves, sporadic arrhyth- 7. Which of the following drugs prescribed preclude the patient in the above might be used as an adjunct to quinidine in the scenario from taking it, you switch him to ther- treatment of the atrial flutter? A 55-year-old woman is admitted to the sur- (D) Esmolol gical intensive care unit after having a coronary (E) Ezetimibe artery bypass grafting of four of her coronary vessels. You prescribe cap- Swan-Ganz catheter, is significantly lower than topril, a medication proven to reduce her it had been post-surgery. You are taking care of a 64-year-old man (E) It increases preload who had just undergone a right hemicolectomy for colon cancer.

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Treatment involves including foods secretin A hormone that is made by glands in the that are high in vitamin C in the diet and taking vita- small intestine whose primary function is the stimu- min C supplements if necessary generic 50mg kamagra fast delivery. Also known as petit mal obtained via surgery is usually sectioned (sliced) order 100mg kamagra fast delivery, seizure discount kamagra 100mg with mastercard. The patient does not actually become unconscious purchase kamagra 50mg with mastercard, section, longitudinal See longitudinal section. The patient may have section, lower segment caesarean See cae- physical, sensory, and thought disturbances. If sedatives are misused or accidentally seizure, febrile A convulsion that occurs in asso- combined, as in the case of combining prescription ciation with a fever. Febrile seizures are common in sedatives with alcohol, they can dangerously infants and young children and are usually of no last- depress important signals that are needed to main- ing importance. The sed rate measures the rate at which red nerve function that is caused by abnormal electrical blood cells in a test tube separate from blood serum activity in a localized area of the brain. Jacksonian over time, becoming sediment at the bottom of the seizures typically cause no change in awareness or test tube. The type of symptoms and seizures expe- of the brain is affected: One part of the body, or mul- rienced depend on where the abnormal electrical tiple body parts confined to one side of the body, activity takes place in the brain, what its root cause is, may start to twitch uncontrollably. Partial seizures and such factors as the patient’s age and general state may involve head turning, eye movements, lip of health. Seizures can be caused by head injuries, smacking, mouth movements, drooling, rhythmic brain tumors, lead poisoning, maldevelopment of the muscle contractions in a part of the body, appar- brain, genetic and infectious illnesses, and fevers. In ently purposeful movements, abnormal numbness, half of patients with seizures, no cause can yet be tingling, and a crawling sensation over the skin. Partial seizures can also include sensory distur- bances, such as smelling or hearing things that are seizure, absence A seizure that takes the form not there or having a sudden flood of emotions. Also known as focal seizure and can be accompanied by blinking or mouth twitch- local seizure. Deficiency of selenium causes which the body becomes rigid) and the clonic phase Keshan disease. Tonic- clonic seizures may or may not be preceded by selenium deficiency See deficiency, selenium. They may last for mere sec- sella turcica A depression in the base of the onds or continue for several minutes. It was clonic seizure does not resolve or if such seizures called the sella turcica (the Turkish saddle) follow each other in rapid succession, the patient because of its resemblance to a saddle used by the needs emergency help. The fluid comes from the prostate, seminal seizure disorder One of a great many medical vesicles, and other sex glands. The sperm are man- conditions that are characterized by episodes of ufactured in the testicles. The seminal fluid helps uncontrolled electrical activity in the brain transport the sperm during orgasm. Some seizure disorders are hereditary, contains sugar as an energy source for sperm. Seizure dis- semen analysis A laboratory test that measures orders are more likely to develop in patients who the amount of semen a man produces and deter- have other neurological disorders, psychiatric con- mines the number and quality of sperm in the ditions, or immune system problems than in others. A semen analysis is usually one of In some cases, uncontrolled seizures can cause the first tests done to help determine whether a man brain damage, lowered intelligence, and permanent has a problem fathering a child (infertility). The seminal vesicles ally involves use of medication, although in difficult contribute fluid to the ejaculate. For exam- ple, raloxifene (brand name: Evista) prevents bone sensory integration dysfunction A neurologi- loss and lowers serum cholesterol as estrogen does, cal disorder in which there is impaired perception but it has been used, like tamoxifen, to block the or processing of sensory input to the brain. In sen- action of estrogen on breast cells and is given to pre- sory integration dysfunction, the processing of infor- vent breast cancer in some high-risk populations. Symptoms range from very mild to debilitating and may involve mutism; mutism; social phobia. It selective serotonin reuptake inhibitor See is most commonly diagnosed in children. Also known of selenium include seafoods; some meats, such as as sensory processing disorder. Sepsis may be associ- ated with clinical symptoms of systemic illness, such septum, interatrial See septum, atrial. Sepsis can be a serious situ- septum, interventricular See septum, ation, a life-threatening condition that requires ventricular. Treatment depends on the type of infection but usually begins with septum, nasal The dividing wall that runs down antibiotics or similar medications. Also known as the middle of the nose, creating two nasal passages, blood poisoning and septicemia. Also with sepsis may be listless, overly sleepy, floppy, known as interventricular septum. For example, a septate uterus is antibodies in the blood that are directed against an one that is divided.

The intrinsic factor–vitamin B12 complex is absorbed by active transport in the distal ileum cheap 50 mg kamagra fast delivery. The appearance of large macrocytic (megaloblastic) red cells in the blood is characteristic of this deficiency buy 50 mg kamagra fast delivery. Vitamin B12 is not synthesized by eukaryotic cells and is normally obtained from microbial synthesis buy kamagra 50 mg otc. Therapeutic uses (1) Vitamin B12 is used to treat pernicious anemia (inadequate secretion of intrinsic factor with subsequent reduction in vitamin B12 absorption) purchase kamagra 100mg. Hypokalemia and thrombocytosis can occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with cyanocobalamin therapy. Most folate is absorbed in the proximal portions of the small intestine and is transported to tissues bound to a plasma-binding protein. Folic acid requires reduction by dihydrofolate reductase to the active metabolite methyltetrahydrofolate. The cofactors of folic acid provide single carbon groups for transfer to various acceptors and are essential for the biosynthesis of purines and the pyrimidine deoxythymidylate. Catabolism and excretion of vitamin B9 is more rapid than that of vitamin B12; hepatic reserves are sufficient for only 1–3 months. Folic acid is used to correct dietary insufficiency (commonly observed in the elderly), as a supplement during pregnancy to decrease the risk of neural tube defects, during lactation, and in cases of rapid cell turnover, such as hemolytic anemia. Leucovorin may be used to reverse the effects of the folate antagonists (see Chapter 12) methotrexate, pyrimethamine, and trimethoprim. Hydroxyurea has been shown effective in reducing painful episodes by about 50%; the necessity of blood transfusions was also shown to be reduced. Hydroxyurea increases the production of fetal hemoglobin, which makes red cells resistant to sickling and reduces the expression of ad- hesion molecules such as L-selectin. The actions of pentoxifylline include increased erythrocyte flexibility and decreased blood viscosity. Myeloid growth factors are glycoproteins produced by many cells including fibroblasts, endo- thelial cells, macrophages, and immune cells that act to stimulate proliferation and differen- tiation of one or more myeloid lineage. Sargramostim is a recombinant protein essentially identical to the native protein. Its princi- pal action is to stimulate myelopoiesis in granulocyte–macrophage pathways as well as megakaryocytic and erythroid progenitor cells. Clinical uses (1) Reduce the duration of neutropenia and incidence of infection in patients receiving myelosuppressive chemotherapy or bone marrow transplantation (2) Mobilize peripheral blood progenitor cells prior to collection (3) For bone marrow graft failure c. Filgrastim is a recombinant protein that stimulates bone marrow production of neutrophils without increasing the number of basophils, eosinophils, or monocytes. Pegfilgrastin is filgrastin with a polypropylene glycol molecule added to the N-terminus. Its clinical uses are similar to those of sargramostim: reduction in the duration of neutrope- nia in patients on anticancer regimens and for patients with chronic severe neutropenia. It is used clinically to prevent severe chemotherapy-induced thrombocytopenia and to reduce the need for platelet transfusions following myelosuppressive chemotherapy for nonmyeloid malignancies. Commercial heparin contains 8–15 repeats of d-glycosamine-l-iduronic acid and d-glucosamine-d-glucu- ronic acid. Commercial preparations are derived from bovine lung or porcine intes- tinal extracts. The clotting factor is inactivated, and intact heparin is released and recycled in a catalytic man- ner. Pharmacologic properties (1) Heparin must be given parenterally (by slow infusion or deep subcutaneous injec- tion); it is not injected intramuscularly because of the potential for hematoma formation. The principal advantage of the low- molecular-weight heparins is a greater pharmacokinetic predictability that allows once- or twice-a-day subcutaneous dosing without the need for monitoring. Therapeutic uses (1) Heparin provides preoperative prophylaxis against deep vein thrombosis. Adverse effects (1) Bleeding is a common adverse effect, especially in older women. Chapter 7 Drugs Used in Anemia and Disorders of Hemostasis 181 (3) Heparin can cause hypersensitivity reactions, including chills, fever, urticaria, and anaphylaxis. Contraindications and drug interactions (1) Heparin is contraindicated in patients who are bleeding (internally or externally) and in patients with hemophilia, thrombocytopenia, hypertension, or purpura. Fondaparinux is a synthetic polysaccharide based on the antithrombin-binding region of heparin. Administered by subcutaneous injection, it behaves like the low-molecular-weight heparins in inactivating factor Xa. Fondaparinux is approved for prophylaxis of thrombus formation in patients undergoing hip or knee surgery, treatment of pulmonary embolism, and deep vein thrombosis. Structure (1) Coumarin derivatives are derived from 4-hydroxycoumarin and include dicumarol, warfarin sodium, and phenprocoumon. Continued production of functional clotting factors requires replenishment of reduced vitamin K from the oxidized form; this reduction is catalyzed by vitamin K epoxide reductase; which is directly inhibited by coumarin derivatives.

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