Respiratory Flashcards
Rifampicin
Use: TB, prophylaxis against meningococcal meningitis and H.influenzae B, treatment of Mycobacterial infections
MOA: inhibit bacterial DNA-dependent RNA polymerase and prevent initiation of mRNA transcription. Resistance arises from genetic mutation of bacterial DNA-dependent RNA polymerases.
Adverse effects: nausea, anorexia, diarrhoea, Abx-assoc. colitis, hepatotoxicity, orange discolouration (sweat, tears, urine), influenza-type symptoms, renal failure, shock, DIC, acute haemolytic anaemia
Contraindications: jaundice, acute porphyria
Interactions: CYP450 inducer (can reduce conc. of oestrogen, warfarin, phenytoin, sulphonylurea
Isoniazid
Use: TB
MOA: prodrug, activated by catalase-peroxidase in mycobacteria. Inhibits enzymes involved in the synthesis of long-chain mycolic acids (unique to cell wall of mycobacteria) and inhibits enzymes required for nucleic acid synthesis. Resistance when used alone.
Adverse effects: N&V, constipation, dry mouth, peripheral neuropathy (high doses; can use pyridoxine in high risk patients), hepatitis, rashes, SLE-like syndrome
Cautions: acute porphyria, alcohol dependence, DM, epilepsy, hx of psychosis, HIV, malnutrition, slow acetylator status (increased SLE risk)
Contraindications: drug-induced liver disease
Interactions: certain foods (tyramine rich, yeast, fermented soya bean, histamine-rich), increases con. of carbamazepine, aminophylline and clearance of theophylline
Pyrazinamide
Use: TB
MOA: pro-drug; converted to pyrazinoic acid by pyrazinamidase (enzyme found in M.tuberculosis). Unclear MOA, but bactericidal.
Adverse effects: hepatotoxicity, N&V, arthralgia, sideroblastic anaemia
Contraindications: acute attack of gout
Interactions: allopurinol (increases risk of hyperuricaemia)
Ethambutol
Use: TB
MOA: arabinose analogue, inhibits arabinosyl transferase, impairing synthesis of mycobacterial cell wall. Bacteriostatic.
Adverse effects: optic neuritis (dose-related), peripheral neuritis, hyperuricaemia gout, nephrotoxicity
Contraindications: optic neuritis, poor vision
Interactions: increases risk of optic neuropathy when given with ethambutol
Beta-2 adrenoceptor agonists
E.g. salbutamol, terbutaline, salmeterol, formoterol
Use: asthma (SABAs to relieve breathlessness; LABAs in step 3 with ICS for chronic asthma), COPD (SABAs to relieve breathlessness; LABAs as 2nd-line Rx), hyperK+ (neb salbutamol as an add on treatment with insulin, glucose, Ca2+ gluconate)
MOA: stimulate beta-2 receptors in SM of bronchi, GIT, uterus and BVs, causing SM relaxation. Also stimulate Na/K ATPase, causing a shift of K+ from EC to IC.
Adverse effects: tachycardia, palpitations, anxiety, tremor, promote glycogenolysis, increase serum lactate (high dose), muscle cramps (LABA)
Cautions: CVD (tachycardia may provoke angina/arrhythmia), give LABA with ICS
Interactions: effectiveness reduced by beta blockers, hypoK+ can result from high-dose neb beta-2 agonists and theophylline and corticosteroids
Antimuscarinic bronchodilators
E.g. ipatropium, tiotropium
Use: COPD (SAMA to relieve breathlessness; LAMA to prevent breathlessness/exacerbations), asthma (SAMA as adjunct to relieve breathlessness; LAMA in step 4 with high-dose ICS for chronic asthma)
MOA: binds to muscarinic receptor, acts as a competitive inhibitor of ACh. Stimulation of muscarinic receptor induces sympathetic responses (increased HR and conduction, reduction of SM tone, reduced secretions from respiratory and GI glands, pupillary dilation)
Adverse effects: dry mouth
Cautions: angle-closure glaucoma, those with or at risk of arrhythmia
Interactions:
Theophyllines
E.g. aminophylline, modified-release theophylline
Use: chronic asthma, reversible airway obstruction
MOA: Inhibit PDE3 and 4 (bronchodilator, increases force/rate of contraction of cardiac muscle, arterial vasodilation), adenosine antagonist (reduces bronchoconstriction), activates histone deacetylases (anti-inflammatory effect), improved ventilation (increased diaphragmatic contractility)
Adverse effects: GI upset, CNS stimulation (insomnia, irritability, dizziness, headaches, occasional seizures), hypotension, arrhythmia, hypoK+, tolerance
Cautions: cardiac arrhythmia, elderly, epilepsy, fever, HTN, peptic ulcer, risk of hypoK+, thyroid disorder
Interactions: hepatic CYP1A2 inhibitors can precipitate toxicity (ciprofloxacin, erythromycin, clarithromycin, fluconazole, ketoconazole)
Inhaled corticosteroids
E.g. beclometasone, fluticasone
Use: asthma (control symptoms and prevent exacerbation, and Rx of chronic asthma), COPD (control symptoms and prevent exacerbations)
MOA: suppress airway inflammatory. Prescribed with LABA as increases adherence to treatment e.g. Seretide = fluticasone + salmetol; Symbicort = budesonide + formoterol
Adverse effects: local e.g. oral thrush, hoarse voice, increased risk of pneumonia (COPD). Systemic over long-term e.g. adrenal suppression, growth retardation, osteoporosis
Cautions: COPD with hx of pneumonia, children (growth suppression)
Oral/parenteral corticosteroids
E.g. hydrocortisone, prednisolone
Use: asthma, suppression of autoimmune disease, cancer, hormone replacement in adrenal insufficiency/hypopituitarism
MOA: up regulate anti-inflammatory genes and down regulate pro-inflammatory genes
Adverse effects: infection risk, DM, osteoporosis, increases catabolism (proximal muscle wasting, skin thinning, easy brushing, gastritis), mood and behavioural changes (insomnia, confusion, psychosis, suicidal ideation), HTN, hypoK+, oedema, Addisonian crisis, adrenal atrophy, chronic glucocorticoid deficiency
Cautions: children, infection
Interactions: increased risk of peptic ulceration and GI bleeding with NSAIDs, enhance hypoK+ if taking beta-2 agonists/theophylline/loop or thiazide diuretics, reduced efficacy by CYP450 inducers (phenytoin, carbamazepine, rifampicin), reduce immune response to vaccines
Sodium cromoglicate
Use: prevent asthma attacks, seasonal allergic rhinitis, allergic conjunctivitis
MOA: mast cell stabilisation, inhibition of sensory C fibre neutrons (antagonism of tachykinins/substance P/neurokinin B), inhibition of accumulation of eosinophils, inhibits B cells switching to IgE production
Adverse effects: cough, wheeze, throat irritation, headache
Cautions: discontinue if eosinophilic pneumonia occurs
Leukotriene receptor antagonist
E.g. Montelukast
Use: mild-moderate asthma, exercise induced bronchoconstriction, hypersensitivity reactions provoked by NSAIDs
MOA: inhibit bronchoconstriction by blocking CysLT1 receptor on bronchial SM.
Adverse effects: headache, GI upset
