Fine skeletal muscle tremor, tachycardia, arrhythmia, hypokalaemia, headache
? Dry mouth, nausea, constipation, headache, urinary retention in men with prostatism (tiotropium), exacerbation of angle-closure glaucoma
? GI upset, CNS stimulation, hypotension, arrhythmia, hypokalaemia, interaction with CYP1A2 inhibitors
Mast cell stabilisation, sensory C-fibre inhibition, inhibition of eosinophil accumulation in lungs, decreases IgE
Decreased T-cell cytokine production, decreased dendritic cell signalling, decreased eosinophil/mast cell deposition in bronchial mucosa, suppression of epithelial shedding/goblet cell hyperplasia
Decreased inflammatory cell activation, decreased mucosal oedema, decreased local generation of prostaglandins and leukotrienes, upregulation of B2-adrenoceptors and improved adenyl cyclase coupling, increased activity of M2 receptors
Quinolones (ciprofloxacin), metronidazole, nitrofurantoin
B-lactams (penicillin, cephalosporins, monobactams, carbapenam), glycopeptides (vancomycin), lipopeptides (daptomycin)
Macrolides (erythromycin), aminoglycosides (gentamicin), tetracyclines, chloramphenicol, lincosamides, fusidic acid, oxazolidinones,
Sulfonamides
Act at presynaptic autoreceptors in nucleus of tractus solitarius to stimulate RVLM (reduce sympathetic outflow) and increase vagal outflow
Increases activity in rostral ventrolateral medulla (RVLM) which leads to decreased sympathetic outflow, which causes a decrease in vasoconstriction, heart rate and myocardial contractility
Direct arterial dilation by reduced Ca2+ entry to smooth muscle cells due to intracellular Na+ depletion
Postural hypotension, lethargy, headache, dizziness, nausea, rhinitis, urinary frequency/incontinence, palpitation
? Dilutional hyponatraemia, hypokalaemia (not spironolactone), hypomagnesaemia, hyperuricaemia, incontinence, ototoxicity, vertigo, impotence, nocturia, hyperlipidaemia, hyperkalaemia (spironolactone), GI upset, antiandrogenic (spironolactone)
Acute heart failure with pre-existing poor left ventricular function, Raynaud’s phenomenon, excessive bradycardia with heart block, bronchospasm, hypoglycaemia with diabetes, raised lipid levels, sleep disturbance, vivid dreams, hallucinations, withdrawal syndrome, interactions with calcium channel blockers
Weak inhibitor of neuronal reuptake of noradrenaline and dopamine thus enhancing mesolimbic and dopaminergic activity, started 1-2 weeks before a quit date, makes quitter less likely to gain weight.
Partial agonist at nicotine receptors, highly selective for CNS subtype involved in addiction, blocks the effect of added nicotine, started 1-2 weeks before a quit date
Maintains plasma nicotine levels above those at which withdrawal symptoms occur
Depressing rate of PGE2 formation in hypothalamus in response to circulating IL-1
? Inhibit production of prostaglandins by COX-1/-2 isoenzymes (prostaglandins increase ability of thermal, mechanical and chemical stimuli to generate action potentials in nociceptive neurons) reduce sensitivity of nociceptive neurons to bradykinin and substance P (released by damaged tissue)
Inhibition of GABA neurons which normally inhibit serotonergic neurons which connect to presynaptic afferent nociceptive fibres in the dorsal horn of the spinal cord and prevent release of pain initiating substance P, glutamate and nitric oxide from the nociceptive neuron
Haemorrhage (greater in elderly/alcohol intake, reversed by IV protamine sulphate (less effective against LMWH), osteoporosis (unfractionated binds to osteoblasts), thrombocytopenia (2% 5-15 days after due to antibodies against heparin-platelet factor 4 complex), hyperkalaemia ( 7 days after due to inhibition of aldosterone secretion)
Haemorrhage, thrombocytopenia, oedema, GI upset
Haemorrhage, fever, hypersensitivity reactions
Bind to substrate binding site and catalytic site on thrombin and so inactivate circulating and clot-bound thrombin, used when heparins have induced thrombocytopenia
LMWH: forms complex with antithrombin III, inactivates factor Xa (4x more potent than unfractionated), promotes tissue factor pathway inhibitor release from vascular wall (inhibits Xa formation), activation of lipoprotein lipase (decrease platelet adhesiveness), unfractionated: binds to platelet factor 4, inhibits platelet aggregation, conformationally alters antithrombin III then forms complex, inactivates thrombin, factors IXa, Xa, XIa, XIIa,
Inhibits hepatic vitamin K epoxide reductase (converts vit K to active form) vitamin K used to synthesise factors II, VII, IX and X
Broad spec antibiotics, amiodarone, cimetidine (CYP2C9 inhibitors), ibuprofen
Phenobarbital, alcohol
Phenytoin
0.9-1.3
3.5-4
2-2.5
Irreversibly inhibits COX-1 and so prevents the synthesis of the platelet aggregating agent thromboxane A2 by platelets throughout their lifespan
Bind to GPIIb/IIIa receptors and block binding of fibrinogen thus reducing platelet aggregation
Irreversibly bind to purinergic ADP receptors on platelet surface, reduces mobilisation of Ca2+ from intracellular stores and reduces expression of GPIIb/IIIa receptors
Haemorrhage less common with streptokinase, tenecteplase binds longest and is least sensitive to inhibitors
Alteplase can cause allergic reaction, hypotension is less common with streptokinase
Reteplase is derived from bacteria, tenecteplase is an analogue of tPA
50% reduction in absorption of cholesterol at brush border of small intestine, reduces plasma cholesterol by 15%, LDL by 20%
Bind bile salts in the gut, bile acid reabsorption is impaired, so synthesis is increased from hepatic cholesterol, upregulation of LDL receptors, 15% fall in circulating LDL
Increased free fatty acid uptake in liver, reduces availability for triglyceride synthesis, increased mitochondrial free fatty acid uptake in heart and skeletal muscle, increased lipoprotein lipase activity, enhanced apolipoprotein production leads to increased plasma HDL
Inhibit enzyme which catalyses rate-limiting step of cholesterol synthesis, upregulation of LDL receptors on hepatocytes, increased clearance of LDL (25-50%)
GI upset, dizziness, blurred vision, headaches, disturbance of LFTs, hepatitis, myalgia, myositis, rhabdomyolysis
GI upset, rash, dizziness, headache, inhibition of warfarin
Unpalatability, constipation, diarrhoea, interference with absorption of acidic drugs
Headache, flushing, dizziness, ankle oedema, heart failure with poor left ventricular function, tachycardia, palpitations, bradycardia, heart block, constipation, nausea, heartburn, gum hyperplasia
Dilutional hyponatraemia, hypokalaemia (not spironolactone), hypomagnesaemia, hyperuricaemia, incontinence, ototoxicity, vertigo, impotence, nocturia, hyperlipidaemia, hyperkalaemia (spironolactone), GI upset, antiandrogenic (spironolactone)
Hypokalaemia due to decreased competition for Na+/K+ pump (diuretics), renal impairment (elderly), hypoxaemia, hypothyroidism (reduced glomerular filtration rate), verapamil and quinidine displace from binding sites and interfere with renal excretion thus raising plasma concentration
Gradual introduction can reduce workload of ischaemic myocardium, restore excitation-contraction coupling, reduce cardiac hypertrophy and fibrosis, reduce myocyte apoptosis and counteract arrhythmias
Inhibit Na+/K+ ATPase in cardiac myocyte membrane, thereby reducing passive Na+/Ca2+ exchange thus retaining Ca2+ inside cell, enhancing myocardial contractility
Inhibits cleavage of ATI to ATII and breakdown of bradykinin by ACE, prevents arterial vasoconstrictive effects of ATII and enhances vasodilatory effects of bradykinin, reduces release of aldosterone
Direct arterial dilation by reduced Ca2+ entry to smooth muscle cells due to intracellular Na+ depletion
Reduced Ca2+ entry and reduced release from ER to smooth muscle cells due to blockage of L-type calcium channels
Inhibits cleavage of ATI to ATII and breakdown of bradykinin by ACE, prevents arterial vasoconstrictive effects of ATII and enhances vasodilatory effects of bradykinin,
Blocks ATII mediated arterial vasoconstriction