Respiratory Stimulants and Pulmonary Surfactants

Respiratory Stimulants and Pulmonary Surfactants

Pulmonary surfactants are used in the management of respiratory distress syndrome (hyaline membrane disease) in neonates and preterm neonates. They may also be given prophylactically to those considered at risk of developing the syndrome. Continuous monitoring is required to avoid hyperoxaemia caused by rapid improvement in arterial oxygen concentration. Pulmonary haemorrhage has been rarely associated with therapy especially in more preterm neonates; obstruction of the endotracheal tube by mucous secretions has also been reported.

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Mucolytics

Mucolytics

Mucolytics are prescribed to facilitate expectoration by reducing sputum viscosity. In some patients with chronic obstructive pulmonary disease and a chronic productive cough, mucolytics can reduce exacerbations; mucolytic therapy should be stopped if there is no benefit after a 4-week trial. Steam inhalation with postural drainage is effective in bronchiectasis and in some cases of chronic bronchitis.

Mucolytics should be used with caution in those with a history of peptic ulceration because they may disrupt the gastric mucosal barrier.

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Bronchodilators

Bronchodilators

The selective beta2 agonists (selective beta2-adrenoceptor agonists, selective beta2 stimulants) such as salbutamol or terbutaline are the safest and most effective short-acting beta2 agonists for asthma. Less selective beta2 agonists such as orciprenaline should be avoided whenever possible. Adrenaline (epinephrine) (which has both alpha- and beta-adrenoceptor agonist properties) is used in the emergency management of allergic and anaphylactic reactions and in the management of croup

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Corticosteroids

Corticosteroids

Corticosteroids are used for the management of reversible and irreversible airways disease. An inhaled corticosteroid used for 3–4 weeks may help to distinguish asthma from chronic obstructive pulmonary disease; clear improvement over 3–4 weeks suggests asthma. Corticosteroids are effective in asthma; they reduce airway inflammation (and hence reduce oedema and secretion of mucus into the airway). An inhaled corticosteroid is used regularly for prophylaxis of asthma when patients require a beta2 agonist more than twice a week, or if symptoms disturb sleep more than once a week, or if the patient has suffered exacerbations in the last 2 years requiring a systemic corticosteroidor a nebulised bronchodilator. Regular use of inhaled corticosteroids reduces the risk of exacerbation of asthma.

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Leukotriene Receptor Antagonists

Leukotriene Receptor Antagonists

Dose and Administration:Prophylaxis of asthma, adult and child over 15 years, 10 mg once daily in the evening; child 6 months–6 years 4 mg once daily in the evening, 6–15 years 5 mg once daily in the evening.

Seasonal allergic rhinitis, adult and child over 15 years, 10 mg once daily in the evening.

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Lipid Regulating Drugs

Lipid Regulating Drugs

Statins:

Simvastatin:

Indications: primary hypercholesterolaemia, homozygous familial hypercholesterolaemia or combined (mixed) hyperlipidaemia in patients who have not responded adequately to diet and other appropriate measures;

prevention of cardiovascular events in patients with atherosclerotic cardiovascular disease or diabetes mellitus.

Contraindications: Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels. Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Nursing mothers. It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk

Dose and Administration: Primary hypercholesterolaemia, combined hyperlipidaemia, 10–20 mg daily at night, adjusted at intervals of at least 4 weeks; usual range 10–80 mg once daily at night. Homozygous familial hypercholesterolaemia, 40 mg daily at night or 80 mg daily in 3 divided doses. Prevention of cardiovascular events, initially 20–40 mg once daily at night, adjusted at intervals of at least 4 weeks; max. 80 mg once daily at night.

Atorvastatin:

Indications: primary hypercholesterolaemia, heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia or combined (mixed) hyperlipidaemia in patients who have not responded adequately to diet and other appropriate measures; prevention of cardiovascular events in patients with type 2 diabetes and at least one additional risk factor for cardiovascular disease

Contraindications: Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels. Women who are pregnant or may become pregnant. atorvastatin may cause fetal harm when administered to a pregnant woman.

Dose and Administration: Primary hypercholesterolaemia and combined hyperlipidaemia, usually 10 mg once daily; if necessary, may be increased at intervals of at least 4 weeks to max. 80 mg once daily; child 10–17 years usually 10 mg once daily. Familial hypercholesterolaemia, initially 10 mg daily, increased at intervals of at least 4 weeks to 40 mg once daily; if necessary, further increased to max. 80 mg once daily (or 40 mg once daily combined with anion-exchange resin in heterozygous familial hypercholesterolaemia); child 10–17 years initially 10 mg daily, increased if necessary after at least 4 weeks to 20 mg once daily. Prevention of cardiovascular events in type 2 diabetes, 10 mg once daily.

Fluvastatin:

Indications: adjunct to diet in primary hypercholesterolaemia or combined (mixed) hyperlipidaemia (types IIa and IIb); adjunct to diet to slow progression of coronary atherosclerosis in primary hypercholesterolaemia and concomitant coronary heart disease; prevention of coronary events after percutaneous coronary intervention.

Contraindications: in patients with active liver disease or unexplained, persistent elevations in serum transaminases. If the patient becomes pregnant while taking this class of drug, therapy should be discontinued and the patient apprised of the potential hazard to the fetus.

Dose and Administration: Hypercholesterolaemia or combined hyperlipidaemia, initially 20–40 mg daily in the evening, adjusted at intervals of at least 4 weeks; up to 80 mg daily may be required; child and adolescent under 18 years, not recommended. Prevention of progression of coronary atherosclerosis, 40 mg daily in the evening. Following percutaneous coronary intervention, 80 mg daily.

Rosuvastatin:

Indications: primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia), mixed dyslipidaemia (type IIb), or homozygous familial hypercholesterolaemia in patients who have not responded adequately to diet and other appropriate measures.

Contraindications: Patients with active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels. Women who are pregnant or may become pregnant. Nursing mothers.

Dose and Administration: Initially 5–10 mg once daily increased if necessary at intervals of at least 4 weeks to 20 mg once daily, increased after further 4 weeks to 40 mg daily only in severe hypercholesterolaemia with high cardiovascular risk and under specialist supervision; elderly initially 5 mg once daily; patient of asian origin, initially 5 mg once daily increased if necessary to max. 20 mg daily.

Ezetimibe:

Indications: administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) in patients with primary (heterozygous familial and non-familial) hyperlipidemia. administered in combination with fenofibrate, is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, Apo B, and non-high-density lipoprotein cholesterol (non-HDL-C) in adult patients with mixed hyperlipidemia. The combination with simvastatin is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments.

Contraindications: Women who are pregnant or may become pregnant. Nursing mothers.

Dose and Administration: adult and child over 10 years, 10 mg once daily.

Simvastatin-Ezetimibe:

Indications: indicated for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia. indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Contraindications: Active liver disease or unexplained persistent elevations in hepatic transaminase levels. Women who are pregnant or may become pregnant.

Dose and Administration: The recommended usual starting dose is 10/20 mg/day as a single daily dose in the evening, with or without food. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10/40 mg/day.

Atorvastatin-Amlodipine:

Indications: indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate.

Contraindications: Pregnancy and Lactation. in patients with active liver disease or unexplained persistent elevations of serum transaminases.

Dose and Administration: Dosage should be adjusted according to each patient’s need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient’s response to each dose level.

Fibrates:

Gemfibrozil:

Indications: hyperlipidaemias of types IIa, IIb, III, IV and V in patients who have not responded adequately to diet and other appropriate measures; primary prevention of cardiovascular disease in men with hyperlipidaemias that have not responded to diet and other appropriate measures.

Contraindications: alcoholism, biliary-tract disease including gallstones; photosensitivity to fibrates; hepatic impairment; pregnancy; breast-feeding.

Dose and Administration: 1.2 g daily, usually in 2 divided doses; range 0.9– 1.2 g daily; child not recommended

Fenofibrate:

Indications: hyperlipidaemias of types IIa, IIb, III, IV, and V in patients who have not responded adequately to diet and other appropriate measures.

Contraindications: gall bladder disease; photosensitivity to ketoprofen; severe hepatic impairment; pregnancy; breast-feeding.

Dose and Administration: 200mg once daily.

Antihistamines

Antihistamines

All antihistamines are of potential value in the treatment of nasal allergies, particularly seasonal allergic rhinitis (hay fever), and they may be of some value in vasomotor rhinitis. They reduce rhinorrhoea and sneezing but are usually less effective for nasal congestion. Antihistamines are used topically in the eye, in the nose and on the skin. Oral antihistamines are also of some value in preventing urticaria and are used to treat urticarial rashes, pruritus, and insect bites and stings; they are also used in drug allergies. Injections of chlorphenamine (chlorpheniramine) or promethazine are used as an adjunct to adrenaline (epinephrine) in the emergency treatment of anaphylaxis and angioedema.

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Local Sclerosants

Local Sclerosants

Local Sclerosants
Ethanolamine Oleate:

Indications: indicated for the treatment of patients with esophageal varices that have recently bled, to prevent rebleeding. sclerotherapy of varicose veins.

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Fibrinolytic Drugs

Fibrinolytic Drugs

Fibrinolytic drugs act as thrombolytics by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi.

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Anticoagulants

Anticoagulants

Parenteral Anticoagulants:

The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a fibrin web enmeshed with platelets and red cells.

They are therefore widely used in the prevention and treatment of deep-vein thrombosis in the legs. Anticoagulants are of less use in preventing thrombus formation in arteries, for in faster-flowing vessels thrombi are composed mainly of platelets with little fibrin. They are used to prevent thrombi forming on prosthetic heart valves.

Heparin:

Indications: Heparin Sodium Injection is indicated for Anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension; Low-dose regimen for prevention of postoperative deep venous thrombosis and pulmonary embolism in patients undergoing major abdominothoracic surgery or who, for other reasons, are at risk of developing thromboembolic disease.

Contraindications: haemophilia and other haemorrhagic disorders, thrombocytopenia (including history of heparin-induced thrombocytopenia), recent cerebral haemorrhage, severe hypertension; severe liver disease (including oesophageal varices), peptic ulcer; after major trauma or recent surgery to eye or nervous system; acute bacterial endocarditis; spinal or epidural anaesthesia with treatment doses of heparin; hypersensitivity to heparin or to low molecular weight heparins.

Dose and Administration:

Treatment of deep-vein thrombosis, pulmonary embolism, unstable angina, and acute peripheral arterial occlusion, by intravenous injection, loading dose of 5000 units or 75 units/kg (10 000 units in severe pulmonary embolism), followed by continuous intravenous infusion of 18 units/kg/hour or treatment of deep-vein thrombosis, by subcutaneous injection of 15 000 units every 12 hours.

Prophylaxis in general and gynaecological surgery (see notes above), by subcutaneous injection, 5000 units 2 hours before surgery, then every 8–12 hours for 7–10 days or until patient is ambulant (monitoring not needed); during pregnancy (with monitoring), 5000– 10 000 units every 12 hours.

Haemodialysis by intravenous injection initially 1000–5000 units, followed by continuous intravenous infusion of 250– 1000 units/hour

Low Molecular Weight Heparins:

Low molecular weight heparins are usually preferred over unfractionated heparin in the prevention of venous thromboembolism because they are as effective and they have a lower risk of heparin-induced thrombocytopenia. Also, the standard prophylactic regimen does not require monitoring. In orthopaedic practice Low molecular weight heparins are probably more effective than unfractionated heparin; fondaparinux can also be used. The duration of action of Low molecular weight heparins is longer than that of unfractionated heparin; once-daily subcutaneous dosage means that they are convenient to use.

Enoxaparin:

Indications: indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE). Treatment of Acute Deep Vein Thrombosis. Prophylaxis of Ischemic Complications of Unstable Angina and Non­Q-Wave Myocardial Infarction. Treatment of Acute ST-Segment Elevation Myocardial Infarction.

Contraindications: see under heparin.

Dose and Administration:

Prophylaxis of deep-vein thrombosis especially in surgical patients, by subcutaneous injection, moderate risk, 20 mg (2000 units) approx. 2 hours before surgery then 20 mg (2000 units) every 24 hours for 7–10 days; high risk (e.g. orthopaedic surgery), 40 mg (4000 units) 12 hours before surgery then 40 mg (4000 units) every 24 hours for 7–10 days.

Prophylaxis of deep-vein thrombosis in medical patients, by subcutaneous injection, 40 mg (4000 units) every 24 hours for at least 6 days and continued until patient ambulant (max. 14 days).Treatment of deep-vein thrombosis or pulmonary embolism, by subcutaneous injection, 1.5 mg/kg (150 units/kg) every 24 hours, usually for at least 5 days.Unstable angina and non-ST-segment­elevation myocardial infarction, by subcutaneous injection, 1 mg/kg (100 units/kg) every 12 hours usually for 2–8 days (minimum 2 days).

Tinzaparin:

Indications: indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium.

Contraindications: contraindicated in patients with active major bleeding, in patients with (or history of) heparin-induced thrombocytopenia, or in patients with hypersensitivity to tinzaparin sodium.

Dose and Administration: Prophylaxis of deep-vein thrombosis, by subcutaneous injection, general surgery, 3500 units 2 hours before surgery, then 3500 units every 24 hours for 7–10 days; orthopaedic surgery (high risk), 50 units/kg 2 hours before surgery, then 50 units/kg every 24 hours for 7–10 days or 4500 units 12 hours before surgery, then 4500 units every 24 hours for 7–10 days. Treatment of deep-vein thrombosis and of pulmonary embolism, by subcutaneous injection, 175 units/kg once daily for at least 6 days (and until adequate oral anticoagulation established)

Treatment of thromboembolic disease in pregnancy [unlicensed indication], by subcutaneous injection, 175 units/kg once daily

Oral Anticoagulants: 

Warfarin:

Indications: indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.

Contraindications:  peptic ulcer, severe hypertension; renal impairment (avoid if creatinine clearance less than 10 mL/minute); pregnancy

Dose and Administration: Whenever possible, the base-line prothrombin time should be determined but the initial dose should not be delayed whilst awaiting the result. For patients who require rapid anticoagulation the usual adult induction dose of warfarin is 10 mg on the first day; subsequent doses depend upon the prothrombin time, reported as INR (international normalised ratio). For patients who do not require rapid anticoagulation, a lower loading dose can be used over 3–4 weeks. The daily maintenance dose of warfarin is usually 3–9 mg (taken at the same time each day). The following indications and target INRs

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