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The most common adverse effects of captopril are skin rash and loss of taste buy malegra dxt 130 mg without a prescription erectile dysfunction treatment without medicine, which are believed to be caused by the sulfhydryl moiety [52] discount malegra dxt 130 mg visa erectile dysfunction pump price. In ′ enalaprilat, a P1 alanine residue was adopted to mimic the methyl functional found in ′ captopril. Alternatively, in lisinopril, an adjacent basic amino acid P1 lysine residue improved potency as a result of a hydrogen bond network formed with several inter- mediary water molecules, as suggested by X-ray diffraction crystallography data [53]. As for the P1 residue containing the chelating group, a hydrophobic residue could be accommodated by the S1 pocket. Moreover, the removed dipeptide sequence of angiotensin I is composed of a basic and a nonpolar ′ ′ amino acid, His-Leu, that corresponds to the polarity pattern of the P1–P2 residues of lisinopril, namely, Lys-Pro. Enalaprilat is only suitable for intravenous administration because, being dicar- boxylated, it exhibits unfavorable ionization characteristics to allow suffcient sta- bility for oral administration. Consequently, enalapril was developed as a prodrug of enalaprilat, in which the chelating carboxylate moiety was converted to the ethyl ester. The prodrug is metabolized in the body by various esterases to afford the parent compound, enalaprilat. As previously mentioned, ximelagatran and dabigatran etex- ilate, two univalent direct thrombin inhibitor prodrugs, also used ethyl esterifcation to improve oral bioavailability (Section 5. Of interest, benazepril has a benzodiazepine ′ ′ core moiety that encompasses the P –P Ala-Pro sequence in enalapril. Fosinopril is a prodrug that is metabolized in vivo to fosinoprilat, in order to overcome similar oral bioavailability problems associated with enalaprilat. Contrary to enalaprilat, fosinoprilat has a phos- phonate functional group as the zinc-chelating moiety. Although the C-domain is mainly responsible for the regulation of blood pressure by converting angiotensin I, the N-domain is principal for the processing of Ac-Ser-Asp-Lys-Pro, a natural hemoregulatory peptide hormone. In order to overcome the negative feedback mechanism, researchers have focused on renin inhibitors as antihypertensive agents. Renin is a highly specifc aspartic protease that selectively cleaves angiotensino- gen to generate angiotensin I, using two aspartic acids at the active site of the enzyme. An important sequence of angiotensinogen is Pro-Phe-His-Leu//Val within which ′ the scissile bond is between P1 Leu and P Val (Figure 5. A succinic acid residue, having aP –P3 4 retro-inverso amide bond, was introduced to reduce the risk of premature degradation by other proteases [55]. The P3 Phe side-chain was replaced by a 1-methylnaphthyl moiety to avoid recognition and degradation by chymotrypsin, a digestive enzyme that particularly cleaves at Phe-His amide bonds. Moreover, a larger bicyclic aromatic P3 moiety is better accommodated by the S3 pocket than the P3 Phe residue of the angiotensinogen. P2 His residue was kept as in angiotensinogen to maintain hydrogen bond interactions with Ser233 of the renin. As for the critical P1 inhibitory residue, a cyclohexylnorstatine moiety, (2R,3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid could more effciently inhibit renin than several other hydroxymethylcarbonyl isosteric inhibitory units that we have substituted. Remikiren is a renin inhibitor with a dihydroxyethylene isostere as the inhibitory transition state mimic [56]. The side-chain of the P1 transition state mimic residue shares a common cyclohexyl- ′ methyl function between the two compounds. The P1 residues in both peptide drugs ′ were designed to resemble angiotensinogen’s P1 Val residue. Although remikiren is a potent orally active inhibitor, its overall oral bioavailability was low due to hepatic clearance. As with the other peptide renin inhibitors, the P1 residue ′ resembles angiotensinogen’s P1 Val residue. They went on to design through computer-assisted molecular modeling methods several hydroxyethylene transition state mimetic inhibitors with a directly linked P1 –P3 moiety that is large. Doing so, the P1–P4 spanning backbone of the aforementioned peptide inhibitors was eliminated. Although not directly mentioned by the researchers in their reports, we believe these computer-assisted modeling methods also involved virtual high throughput screening that we have briefy touched on (Section 5. Interestingly, the P1 cyclohexylmethyl function found in the aforementioned peptide inhibitors is replaced by an isopropyl function in aliskiren that occupies the same S1 subsite. We believe that this computer-assisted design was possible because the S1–S3 cavity is a large hydrophobic area in which improving ft (e. Moreover, the researchers had the resources to perform several X-ray diffraction crystallography studies that greatly accelerated their discoveries. Indeed, X-ray diffraction crystallography data permitted the team to exploit a 9 Å deep, narrow, and well-defned hydrophobic S3 subpocket by implementing a long hydrophobic ether side-chain to the P1–P3 moiety of aliskiren. In nonpeptide aliskiren, the S3 subpocket interactions, along ′ with improved interactions at the S2 pocket, could suffciently compensate for the lack of S2 and S4 subsites interactions. Orally active aliskiren, designed through molecular modeling techniques, is an octanamide transition state renin inhibitor with good water solubility and low lipophilicity. We expect that future renin inhibitors will have several structural features that are similar to aliskiren so as to take advantage of its nonpeptide benefts. The discovery of cephalosporin compounds from Cephalosporium acremonium is attributed to Giuseppe Brotzu in 1948, and cephalosporin C was subsequently isolated at the University of Oxford [63]. In consideration that the biosynthesis of penicillin G and cephalosporin C begin from a tripeptide comprising of l-α-aminoadipic acid, l-cysteine, and d-valine, in a sense, most antibiotics in the penicillin and cephalosporin classes are peptide drugs (Figure 5. Penicillin antibiotics are known to inhibit a bacterial enzyme, dd-transpeptidase, also known as penicillin-binding protein and serine-type d-Ala d-Ala carboxypeptidase, and interfere with the cross-linking of peptidoglycan chains of the enzyme to form rigid bacterial cell walls. Bacteria that are resistant to penicillins secrete an enzyme, -lactamase, which breaks the drug’s -lactam ring, and thereby inactivating the drug. Using a boosting peptide inhibitor to prevent -lactamase from metabolizing -lactam antibiotics is common practice. Clavulanic acid is a biosynthetic product of amino acid arginine and sugar glyceraldehyde-3-phosphate isolated from Streptomyces clavuligerus [64]. Potassium clavulanate is available as combination penicillin products of amoxicillin-clavulanate and ticarcillin-clavulanate, to inhibit bacterial -lactamase and subsequently overcome bacterial resistance. Although clavulanate, sulbactam and tazobactam share the -lactam ring that is characteristic of -lactam antibiotics, for example, penicillins and cephalosporins, these compounds are not exploited for their antibacterial properties but more for their activity as competitive inhibitors of -lactamase. In a similar manner, cilastatin protects -lactam antibiotic imipenem from being degraded by human renal enzyme dehydropeptidase, and prolongs the antibacterial effect of imipenem [66]. Lacking a -lactam ring, cilastatin is a cysteine analog that does not itself have any antibacterial activity. A protein is introduced within the active site, where its cleavage is coordinated by a water molecule and two aspartic acid residues found at the base of the active site of the protease. For several cases of aspartic protease inhibitors, another water molecule anchors the inhibitor to the fap. As the P2 residue, a methylcysteine was preferred by the S2 subsite over the asparagine of the substrate. In our design, we attempted to increase steric bulk in order to balance hydrophilicity and hydrophobicity, in order to increase desolvation entropy [68]. In other words, a more hydrophobic drug would be more entropically favored to release water molecules as the drug and active site undergo complete or partial desolvation upon binding. Moreover, the increase steric bulk would also reduce fexibility to the drug molecule.

Immunoglobulin must be given as soon as possible after exposure discount 130 mg malegra dxt mastercard impotence solutions, but may be administered up to 7 days after the first vaccine is given order malegra dxt mastercard erectile dysfunction doctors in louisville ky. Infection is usually acquired from unpasteurised milk products or handling raw meat. These include: » long sleeved disposable gown, » vinyl or rubber apron if the patient is bleeding, » two pairs of latex gloves, one below the gown and one over the gown, » disposable face mask preferably with a visor, » goggles if a mask without the visor is used, and » waterproof boots or 2 pairs of overshoes, one over the other. Exclude alternate diseases (see above) by means of appropriate laboratory testing, keeping safety precautions in mind. With medical therapy as above, cure is achieved in about half, improvement in about a quarter and no response in about a quarter of cases. Test any person resident in, or returning from, a malaria area and who presents with fever (usually within 3 months of exposure). The progression to severe falciparum malaria is rapid and early diagnosis and effective treatment is crucial. Pregnant women and young children up to 5 years of age are at particularly high risk of developing severe malaria. Progression to severe malaria may occur and present with the following additional clinical features: » sleepiness, unconsciousness or coma, convulsions, » respiratory distress and/or cyanosis, » jaundice, » renal failure, » shock, » repeated vomiting, » hypoglycaemia, and » severe anaemia (Hb < 6 g/dL). Thick films are more sensitive than thin films in the detection of malaria parasites. Note: If neither microscopy nor rapid tests are available diagnosis should be made on the basis of clinical symptoms. Give all first doses of drugs under supervision and observe patients for at least an hour. Follow with: • Artemether/lumefantrine 20/120 mg, oral, 4 tablets/dose with fat- containing food or full cream milk to ensure adequate absorption. An increase in parasitaemia may occur within 24 hours due to release of sequestrated parasites but a reduction should be seen after 48 hours. Consider concomitant bacteraemia in patients with severe malaria, especially if they have neutrophilia. Muscle relaxants should be used sparingly and may exacerbate autonomic instability. For fever combine with mechanical cooling: • Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses per 24 hours. A rash develops on about the third day of illness in about two thirds of patients with R. Note: This is inferior to doxycycline, which should be commenced as soon as possible. Initial symptoms are abdominal pain, headache and fever with diarrhoea developing only late. Bacteraemia is common initially, subsequently stool culture has the highest yield. This is of vital importance in food handlers, who must not be permitted to return to work until stools are negative. The vesicles in shingles often contain purulent material, and erythema is a cardinal feature of shingles. If there is suspected associated bacterial cellulitis: • Flucloxacillin, oral, 500 mg 6 hourly for 5 days. New patients: all unless contra-indicated • Tenofovir + lamivudine + efavirenz or nevirapine. Contra-indications or toxicity to tenofovir: • Zidovudine + lamivudine + efavirenz or nevirapine. Contra-indications to both tenofovir and zidovudine: • Stavudine + lamivudine + efavirenz or nevirapine. In all other patients where serum creatinine is < 100 micromol//L the calculated creatinine clearance is likely to be > 50 mL/minute and they can safely start tenofovir. If this does not happen on the first regimen then this is nearly always due to poor adherence. Repeat viral load three months later provided the patient is sufficiently adherent. Fasting lipid levels should be done three months after starting lopinavir/ritonavir. Lopinavir/ritonavir is associated with a higher risk of dyslipidaemia than atazanavir/ritonavir. Patients with persistent dyslipidaemia despite switching, qualify for lipid lowering therapy. Many statins (including simvastatin) cannot be used with protease inhibitors, as protease inhibitors inhibit the metabolism of the statin resulting in extremely high blood levels. Patients who fail to respond to lifestyle modification and have hypertriglyceridemia, treat with a fibric acid derivative, e. Zidovudine does not need to be stopped with mild anaemia and/or neutropenia, but must be stopped and replaced with an alternative drug if: » anaemia is symptomatic, » anaemia is severe (Hb below 6. With mild rashes nevirapine and efavirenz can be continued with careful observation and the rash will often subside. If mild rash occurs on nevirapine during the dose lead-in phase (200 mg daily) do not increase the dose to 200 mg 12 hourly until the rash improves. If rash worsens or does not improve within a week discontinue efavirenz or nevirapine. If nevirapine has been stopped due to cutaneous hypersensitivity then efavirenz can be substituted provided that the rash has settled and that the reaction was not life-threatening (either Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis). The clinical symptoms of hyperlactataemia are non-specific and may include: » nausea, » vomiting, » abdominal pain, » weight loss, » malaise, » liver dysfunction (due to steatosis), and » tachycardia. Send blood for lactate levels (check with your local laboratory for specimen requirements for lactate). Monitor serial lactate measurements (initially weekly) until the lactate has returned to within the normal range. If the patient is on a first line regimen, continue the efavirenz or nevirapine and add lopinavir/ritonavir. If the patient is on the second line regimen, continue with lopinavir/ritonavir alone. Note: Many patients will remain with a suppressed viral load when treated with a boosted protease inhibitor only. If the patient is on a first line regimen then the lopinavir/ritonavir can be stopped when the tenofovir and lamivudine are started. High dose vitamin B, especially riboflavin and thiamine, may have a role in therapy. The commonest presentation is with enlarging lymph nodes, often with extensive caseous necrosis. This is not always feasible and an earlier switch to oral fluconazole may be considered if there has been a good clinical response, i.

Warnings/precautions • Use with caution in patients with the following conditions: kidney disease especially renal artery stenosis malegra dxt 130 mg without prescription erectile dysfunction at 25, drugs that cause bone marrow depression discount 130mg malegra dxt erectile dysfunction pumps side effects, hypovolemia, hyponatremia, cardiac or cerebral insufficiency, collagen vascular disease, lupus ery- thematosus, scleroderma, patients undergoing dialysis. Serious: bone marrow depression (neutropenia, agranulocytosis), hypotension, angioedema, hyperkalemia, oliguria, chest pain, angina, tachycardia, asthma, bronchospasm, autoimmune symptom complex (see Editorial Comments), hepatitis, liver failure. Clinically important drug interactions • Fosinopril increases toxicity of following drugs: lithium, azoth- ioprine, allopurinol, potassium-sparing diuretics, digoxin. Nearly every large randomized clinical trial examining their use has been favorable. Treatment with this class of drug is the gold standard in patients with left ventricular systolic dysfunction. Mechanism of action: Inhibits sodium and chloride reabsorp- tion in proximal part of ascending loop of Henle. Contraindications: Hypersensitivity to sulfonamides, anuria, hepatic coma, severe electrolyte depletion. Warnings/precautions • Use with caution in patients with the following conditions: hepatic cirrhosis, depressed renal function, elderly. Advice to patient • Change position slowly, in particular from recumbent to upright, to minimize orthostatic hypotension. Sit at the edge of the bed for several minutes before standing, and lie down if feeling faint or dizzy. Clinically important drug interactions • Drugs that increase effects/toxicity of loop diuretics: other nephrotoxic or ototoxic drugs, amphotericin B, steroids. Parameters to monitor • Serum electrolytes (K, Na, Cl, bicarbonate, Ca, Mg, uric acid). In elderly the following symptoms may occur: lightheadedness, dizziness, vomiting, muscle cramps, bladder spasm, urinary frequency. Editorial comments • Oral furosemide is the drug of first choice for therapy for fluid overload states caused by mild to moderate heart failure. Adjustment of dosage • Kidney disease: Creatinine clearance 30–60 mL/min: 300 mg b. Warnings/precautions • Use with caution in patient with renal insufficiency, elderly. Clinically important drug interactions • Drugs that decrease effect/toxicity of gabapentin: antacids. Editorial comments • Gabapentin is used as an adjunct in the treatment of partial and secondary generalized seizures in adults. Adjustment of dosage • Kidney disease: Creatinine clearance <30 mL/min, serum creatinine >2. Warnings/precautions • Use with caution in patients with impaired cardiovascular function, kidney disease. Clinically important drug interactions: Aminoglycosides, ampho- tericin B increase effects/toxicity of gallium nitrate. If serum calcium level returns to normal within 5 days, discontinue drug treatment. Adjustment of dosage • Kidney disease: Creatinine clearance >60 mL/min: usual dose q8h; creatinine clearance 40–59 mL/min: usual dose q12h; creatinine clearance 20–39 mL/min: usual dose q24h; creati- nine clearance >20 mL/min: half dose q48h. Mechanism of action: Binds to ribosomal units in bacteria, inhibits protein synthesis. Susceptible organisms in vivo: Staphylococci (penicillinase and nonpenicillinase), Staphylococcus epidermidis, Acinetobacter sp, Citrobacter sp, Enterobacter sp, Escherichia coli, Klebsiella sp, Proteus sp, Providencia sp, Pseudomonas sp, Serratia sp. Editorial comments • The usual duration of treatment with gentamicin is 7–10 days. There is a low risk of toxicity in patients who have normal renal function and do not receive high-dose gentamicin longer than the recommended period. Mechanism of action: Stimulates release of insulin from pancre- atic beta cells; decreases glucose production in liver; increases sensitivity of receptors for insulin, thereby promoting effective- ness of insulin. Dose is best administered before breakfast or, if taken twice a day, before the evening meal. Contraindications: Hypersensitivity to glimepiride, diabetes com- plicated by ketoacidosis. Mechanism of action: Stimulates release of insulin from pancre- atic beta cells; decreases glucose production in liver; increases sensitivity of receptors for insulin, thereby promoting effective- ness of insulin. Dose is best administered before breakfast or, if taken twice a day, before the evening meal. Contraindications: Hypersensitivity to glipizide, diabetes compli- cated by ketoacidosis. Warnings/precautions • Current data suggest that there is an increased risk of cardio- vascular mortality with oral hypoglycemic drugs. Patients should be educated concerning the signs and symp- toms of hypoglycemia and how it can be prevented or reversed. The combination with the drug you are taking may result in a disulfiram reaction: flushing, sweating, palpitation, nausea, vomiting, abdominal cramps. For moderate hypo- glycemia, administer fruit juices (1/2 cup orange juice), honey, sugar cubes (2), or corn syrup. Follow this with milk or sandwich which are sources of longer-acting carbohydrate. Continue moni- toring to detect secondary failure after initial success; failure rate of oral hypoglycemic agent is 5–15% per year after 5 years of therapy. These are the best indices of glycemic control as they are indications of blood glucose over the pre- vious 6–10 weeks. Editorial comments • In most cases, institute drug therapy only if a trial of 6–8 weeks of appropriate dietary control has not been successful in achiev- ing satisfactory glycemic control. Mechanism of action: Stimulates production of glucose from liver glycogen stores (glycogenolysis). Onset of Action Peak Effect Duration 5–20 min 20–30 min 60–120 min Pregnancy: Category B. Contraindications: Hypersensitivity to beef or porcine protein, known pheochromocytoma. Warnings/precautions • Use with caution in patients with history of pheochromocy- toma or insulinoma, kidney or liver disease or in emaciated or undernourished patients. Advice to patient • Carry identification card at all times describing disease, treat- ment regimen, name, address, and telephone number of treating physician. Clinically important drug interactions • Drug that decreases effects/toxicity of glucagon: phenytoin. If symptoms of hypoglycemia occur at home, advise patient to take a glass of fruit juice, honey (2–3 teaspoons), 1 or 2 sugar tablets, or corn syrup dissolved in water.

Over-rapid reduc- ton in blood pressure is hazardous and can lead to reduced organ perfusion and cerebral infarcton discount malegra dxt 130 mg overnight delivery erectile dysfunction net doctor. Hypertension in Pregnancy This is defned as a sustained diastolic blood pressure of 90 mmHg or more buy malegra dxt american express impotence psychological. If diastolic blood pressure is greater than 95 mmHg, methyldopa is the safest drug. Beta- blockers should be used with cauton in early pregnancy, since they may retard fetal growth; they are efectve and safe in the third trimester. Women who are taking these drugs and become pregnant should have their anthyperten- sive therapy changed immediately. Pre-eclampsia and eclampsia: If pre-eclampsia or severe hyper- tension occurs beyond the 36th week of pregnancy, delivery is the treatment of choice. For acute severe hypertension in pre- eclampsia or eclampsia, intravenous hydralazine can be used. Magnesium sulphate is the treatment of choice to prevent eclamptc convulsions in eclampsia and severe pre-eclampsia. Contraindicatons Signifcant aortc stenosis, sinoatrial node disease, hypersensitvity to dihydropyridines, cardiogenic shock, unstable angina; interactons (Appendix 6d). Precautons Hypotension, myocardial infarcton, impaired renal functon sick-sinus syndrome, severe ventricular dysfuncton, hypertrophic cardiomyopathy, severe aortc stenosis, eld- erly, children, pregnancy (Appendix 7c); lac- taton; hepatc impairment (Appendix 7a). Adverse efects Arrhythmias, postural hypotension; dizziness, ankle edema, hypoesthesia, fatulence, dizziness, blurred vision, facial fushing, dyspnoea, asthenia, muscle cramps, conducton system delay, abdominal pain, headache; sleep disturbances, fatgue. Dose Oral Adult-75 to 225 µg/day in two divided doses, increase gradually every two weeks. Precautons Depressive illness; concurrent anthypertensive therapy, cerebrovascular disease; porphyria; interactons (Appendix 6a, 6c); pregnancy (Appendix 7c). Adverse Efects Dry mouth; sedaton; dizziness; nausea; nocturnal restlessness; occasionally rashes; cardiac arrhythmias; systemic lupus erythmatosus; anxiety; constpaton; abdominal pain; hallucinaton; impotence and depression. Enalapril* Pregnancy Category-D Schedule H Indicatons Heart failure (with a diuretc); preventon of symptomatc heart failure and preventon of coronary ischaemic events in patents with lef ventricular dysfuncton; hypertension; renal hypertension. Dose Oral Adult- Hypertension: initally 5 mg once daily; if used in additon to diuretc. Usual maintenance dose 10 to 20 mg once daily; In severe hypertension may be increased to max. Risk of very rapid fall in blood pressure in volume-depleted patents; treatment should therefore be initated with very low doses. High-dose diuretc therapy (furosemide dose greater than 80 mg) should be discontnued, or dose signifcantly reduced, at least 24 h before startng enalapril (may not be possible in heart failure-risk of pulmonary oedema). If high-dose diuretc cannot be stopped, medical supervision advised for at least 2 h afer administraton or untl blood pressure stable. Avoid enalapril during dialysis with high-fux polyacrilonitrile membranes and during low- density lipoprotein apheresis with dextran sulphate ; also withhold before desensitzaton with wasp or bee venom. Adverse Efects Dizziness; headache; less commonly nausea; diarrhoea; hypotension (severe in rare cases); dry cough; fatgue; asthenia; muscle cramps; rash and renal impairment; rarely, vomitng; dyspepsia; abdominal pain; constpaton; glossits; stomatts; ileus; anorexia; pancreatts; liver damage; chest pain; palpitatons; arrhythmias; angioedema; bronchospasm; rhinorrhoea; sore throat; pulmonary infltrates; paraesthesia; vertgo; nervousness; depression; confusion; drowsiness or insomnia; pruritus; urtcaria; alopecia; sweatng; fushing; impotence; Stevens-Johnson syndrome; toxic epidermal necrolysis; exfoliatve dermatts; pemphigus; taste disturbance; tnnitus; blurred vision; electrolyte disturbances and hypersensitvity- like reactons (including fever; myalgia; arthralgia; eosinophilia and photosensitvity) reported; azotemia; acute renal failure; taste disturbances. Slow intravenous injecton Adult- Hypertensive crisis (including during pregnancy): 5 to 10 mg diluted with 10 ml Sodium Chloride 0. Intravenous infusion Adult- Hypertensive crisis (including during pregnancy: initally 200 to 300 µg/min; maintenance usually 50 to 150 µg/min. Contraindicatons Idiopathic systemic lupus erythematosus; severe tachycardia, high output heart failure, myocardial insufciency due to mechanical obstructon; cor pulmonale; dissectng aortc aneurysm; porphyria; angina; mitral valvular heart disease; rheumatc disease. Precautons Hepatc impairment (Appendix 7a); renal impairment; coronary artery disease (may provoke angina, avoid afer myocardial infarcton untl stabilized); cerebrovascular disease; check acetylator status before increasing dose above 100 mg daily; test for antnuclear factor and for proteinuria every 6 months; coronary artery disease; alcohol intake; lactaton (Appendix 7b); occasionally over-rapid blood pressure reducton even with low parenteral doses; interactons (Appendix 6b, 6c); pregnancy (Appendix 7c). Heart failure: initally 25 mg daily on waking up, increasing to 50 mg daily if necessary. Contraindicatons Severe renal or severe hepatc impairment; hyponatraemia; hypercalcaemia; refractory hypokalaemia; symptomatc hyperuricaemia; Addison’s disease; gout; diabetes mellitus; persistng hypercalcaemia; anuria; sulphonamide allergy. Precautons Renal and hepatc impairment (Appendix 7a); lactaton (Appendix 7b); elderly (reduce dose); may cause hypokalaemia; may aggravate diabetes mellitus and gout; may exacerbate systemic lupus erythematosus; porphyria; severe heart failure; edema; hyperlipidemia; interactons (Appendix 6a, 6b, 6c); pregnancy (Appendix 7c). Dose Hypertension and diabetc nephropathy: Adult- 50 mg once daily, increased to 100 mg daily as single dose or in two divided doses, if needed. Precautons Pre-existng heart, liver or kidney diseases, diabetes, lactaton, volume depleted patents, renal artery stenosis, monitor serum potassium concentraton, elderly, interactons (Appendix 6a). Adverse efects Abdominal pain, edema, palpitaton, back pain, dizziness, sinusits, upper respiratory tract infecton, rash, gastrointestnal disturbances, transient elevaton of liver enzymes, impaired renal functon, taste disturbances, hyperkalaemia, arthralgia, thrombocytopenia, vasculits. Dose Oral Adult- Hypertension in pregnancy: initally 250 mg 2 to 3 tmes daily; if necessary, gradually increased at intervals of 2 or more days (max 3g daily). Precautons History of hepatc impairment (Appendix 7a); renal impairment; blood counts and liver- functon tests advised; history of depression; positve direct Coomb test in up to 20% of patents (afects blood cross-matching); interference with laboratory tests; lactaton; pregnancy (Appendix 7c); interactons (Appendix 6b, 6c). May impair ability to perform skilled tasks; for example operatng machinery; driving. Adverse Efects Tend to be transient and reversible including sedaton; dizziness; lightheadedness; postural hypotension; weakness; fatgue; headache; fuid retenton and oedema; sexual dysfuncton; impaired concentraton and memory; depression; mild psychosis; disturbed sleep and nightmares; drug fever; infuenza-like syndrome; nausea; vomitng; constpaton; diarrhoea; dry mouth; stomatts; sialadenits; liver functon impairment; hepatts; jaundice; rarely, fatal hepatc necrosis; bone- marrow depression; haemolytc anaemia; leukopenia; thrombocytopenia; eosinophilia; parkinsonism; rash (including toxic epidermal necrolysis); nasal congeston; black or sore tongue; bradycardia; exacerbaton of angina; myalgia; arthralgia; paraesthesia; Bell palsy; pancreatts; hypersensitvity reactons including lupus erythematosus- like syndrome; myocardits; pericardits; gynaecomasta; hyperprolactnaemia; amenorrhoea; urine darkens on standing. Dose Oral Adult- Hypertension (as sustained-release tablets): usual range 20 to 100 mg daily in 1 to 2 divided doses. Contraindicatons Cardiogenic shock, advanced aortc stenosis, within 1 month of myocardial infarcton, unstable or acute atacks of angina, porphyria; hypersensitvity. Precautons Stop if ischaemic pain occurs or existng pain worsens shortly afer startng treatment; poor cardiac reserve; heart failure or sig- nifcantly impaired lef ventricular functon; monitor drug response in cirrhosis patents; blood pressure monitoring; calcium channel blockers; reduce dose in hepatc impairment; diabetes mellitus; may inhibit labour; lacta- ton (Appendix 7b); pregnancy (Appendix 7c); interactons (Appendix 6b, 6c). Adverse Efects Headache; fushing; dizziness; lethargy; tachycardia; palpitatons; gravitatonal oedema (only partly responsive to diuretcs); rash (erythema multforme reported); pruritus; urtcaria; nausea; constpaton or diarrhoea; increased frequency of micturiton; eye pain; visual disturbances; gum hyperplasia; paraesthesia; myalgia; tremor; impotence; gynaecomasta; depression; telangiectasis; cholestasis; jaundice; exacerbated angina; cardiovascular collapse; ankle swelling; gastrointestnal upset; reversible gingival hyperplasia. Dose Reducton in risk of myocardial infarcton, stroke, and death from cardiovascular causes: Inital dose of 2. Hypertension:The recommended inital dose for patents not receiving a diuretc is 2. Precautons Impaired renal functon, impaired liver functon, diabetes mellitus (increased risk of hyperkalemia), patents undergoing surgery, history of angioedema; symptomatc hypotension is most likely to occur in patents who have been volume- and/or salt-depleted as a result of prolonged diuretc therapy, dietary salt restricton, dialysis, diarrhoea, or vomitng. Adverse Efects Hypotension, cough, asthenia, dizziness, headache, angioneurotc edema, hypersensitvity reactons, erythema multforme, toxic epidermal necrolysis, Stevens Johnson syndrome, hepatc necrosis, pancreatts, pancytopenia, thrombocytopenia. Precautons Impaired pulmonary functon; hypothyroidism; renal impairment; ischaemic heart disease; impaired cerebral circulaton; hyponatraemia; raised intracranial pressure; elderly; hypothermia; monitor blood pressure and blood-cyanide concentraton; also blood-thiocyanate concentraton if given for more than 3 days; avoid sudden withdrawal (reduce infusion over 15-30 min to avoid rebound efects); pregnancy (Appendix 7c); lactaton; interactons (Appendix 6b); hepatc impairment (Appendix 7a). Adverse Efects Severe hypotension; efects associated with over-rapid reducton in blood pressure include headache; dizziness; retching; abdominal pain; perspiraton; palpitatons; apprehension; retrosternal discomfort; rarely, reduced platelet count; acute transient phlebits; muscle twitching; hypothyroidism; increased anaerobic metabolism. Adverse efects associated with excessive concentraton of cyanide metabolite include tachycardia; sweatng; hyperventlaton; arrhythmias; marked metabolic acidosis (discontnue infusion and give antdote). Terazosin Pregnancy Category-C Schedule H Indicatons Mild to moderate hypertension, benign prostatc hyperplasia.

F. Marcus. Schreiner College.