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  1. Drugs A guide for ward staff Mark Baxter MB ChB SHO in Cardiothoracic Surgery

  2. Summary • Analgesia • Anti-emetics • Gastro protection • Diuretics • Inhalers • Beta (β) blockers • ACE inhibitors • Calcium channel blockers

  3. Analgesia • W.H.O. analgesic ladder • Paracetamol (weak NSAIDs) • Add weak opiates (eg codeine, dihydrocodeine) • Add non-opiates (eg ibuprofen) • Strong opiates (morphine, oxycodone, fentanyl) • Add non-opiates (eg diclofenac)

  4. Analgesia • Most effective if given “by the clock” • Pain can cause • Tachypnoea • Shallow breathing leads to atelectasis & infection • Hypertension • Tachycardia • Urinary retention

  5. Analgesia - NSAIDs • Mechanism • Prostaglandins promote pain, fever, inflammation; supports platelets & protects stomach lining against acid • NSAIDs inhibit prostaglandin production • Effects • Pain relief, antipyretic, anti-inflammatory • Bleeding, peptic ulcer disease, increased cardiac risk

  6. Analgesia – opiates/opioids • Activates μ-receptors in brain & spinal cord • Effects • Analgesia • dysphoria • Nausea • Note, p.r.n. morphine is not a “4 hrly” drug • Titrate to pain, give as often as needed • Except Oxynorm, which is 4hrly!

  7. Anti-emetics • Cyclizine; 50mg; PO/IV/IM/sc; TDS max • Anti-histamine • Works in the brain (chemoreceptor trigger zone - CTZ) • Caution in prostatic hypertrophy/urinary retention (due to anti-muscarinic activity) • Metoclopramide (Maxalon); 10mg; TDS max; PO/IV/IM/sc • Dopamine receptor antagonist • Acts in CTZ & as a pro-kinetic (muscarinic activity) • Gastric emptying

  8. Anti-emetics • Ondansetron; 4mg; IM/slow IV • Licenced for chemo/radiotherapy & PONV • Not for general n&v use on wards • Completely different to cyclizine/metoclopramide (no muscarinic or dopamine receptor activity) • Works in the brain (blocks vagal activity to vomiting centre in medulla & CTZ)

  9. Anti-platelets • Aspirin (acetylsalicylic acid) – an NSAID • 75mg – anti-platelet dose • 300-900mg qds – analgesic/anti-pyretic dose • In high doses inhibits prostaglandins • Low doses inhibit platelet aggregation & therefore reduces blood clots • Avoid in under-12s!

  10. Gastro protection • Ranitidine • H2 receptor antagonist (a type of antihistamine) • Blocks action of histamine in parietal cells of stomach • Thus inhibits acid production • 12hrly action

  11. Gastro protection • Lansoprazole/omeprazole • Proton pump inhibitor • Irreversibly block the H+/K+ ATPase system – the proton pump • Thus inhibits acid production • 24hr action

  12. Diuretics • Increases rate of urine excretion • Decreases extracellular fluid volume • Lowers BP (but not due to volume loss) • Water follows sodium in the kidney

  13. Diuretics • Thiazide diuretics • Bendroflumethiazide (bendrofluazide/BFZ) • Inhibits Na+/Cl- reabsorption from DCT

  14. Diuretics • Loop diuretics • Furosemide, bumetanide • Inhibits contransporter in thick ascending limb of LoH

  15. Diuretics • Potassium sparing diuretics • Spironolactone • Amiloride

  16. Diuretics • Combinations • Co-amilofruse (amiloride with furosemide) Others • Caffeine – inhibits tubular Na+ reabsorption & incr GFR • Alcohol, water – inhibits ADH (vasopressin) secretion • Cranberry juice

  17. Alpha and beta actions • Alpha and beta adrenoreceptors • Found in smooth muscle throughout body & cardiac muscle • Respond to catecholamines (e.g. adrenaline/noradrenaline) in different ways

  18. Alpha • Mainly stimulated by noradrenaline • Constricts blood vessels • Relaxes GI tract

  19. Beta • Two main types • β1 • Heart & cerebrum • Stimulates heart beat • β2 • Lung, smooth muscle, cerebellum • Bronchiole dilatation • Relaxes smooth muscle

  20. Blood pressure • Controlled by • Alpha & beta receptors • Also affect breathing • Kidneys • Heart itself (cardiac output)

  21. Alpha blockers • Doxazosin, alfuzosin, tamsulosin • Blocks alpha receptors • Effects • Vasodilatation – lowers BP • Relaxes smooth muscles (e.g. in bladder neck in prostatic enlargement)

  22. Beta (β) blockers • Atenolol, sotalol, labetalol, propanolol • Prevents stimulation of the β receptors • Some are more cardio specific (β1) • Preferred in asthmatics • But they are NOT exclusive to β1 • Benefits • Slow the heart rate • Side effects • Constricts bronchioles (caution in asthma/COPD)

  23. Kidney control • Kidneys detect low BP • Release renin • Converts angiotensinogen to angiotensin I • ACE converts angiotensin I to angiotensin II • Angiotensin II is a potent vasoconstrictor, also stimulates other agents to raise BP • aldosterone, vasopressin (ADH)

  24. Angiotensin II AnaesthesiaUk.com

  25. Angiotensin Converting Enzyme (ACE) inhibitors • Inhibit formation of angiotensin II • Lisinopril, perindopril, ramipril • Benefits • Effective • Reno-protective, prevent diabetic nephropathy • Reduces post-MI mortality, prevent CCF • Side effects • Renal impairment (reduces renal blood flow) • Watch for pts on ACEi, diuretic & NSAID!

  26. ACE inhibitors • Perindopril • EUROPA: significant reduction in post-MI mortality • Ramipril • HOPE trial: significant reduction in MI, stroke, CVS death in high risk patients

  27. Angiotensin II receptor antagonists • Losartan, candesartan • Newer, more expensive • Used in pts intolerant of ACEi • Can be more effective • directly prevents action of A2 • ACEi does not totally prevent A2 production • Sometimes used together with ACEi

  28. Calcium Channel Blockers • Amlodipine, felodipine, nifedipine • Calcium used by excitable cells • Smooth muscle, heart muscle • CCBs block the calcium channels • decreases force of muscle contraction • relaxes blood vessels to lower BP • Reduces the rate, and work load of the heart

  29. Inhalers • Bronchodilators • Short acting (salbutamol, iprotropium) • Long acting (salmeterol) • Steroids • fluticasone • beclometasone • Combinations • Seretide (Serevent (salmeterol) + Flixotide (fluticasone) )

  30. Inhalers & asthma • Asthma • Diagnosed with reversibility studies • Shows improvement on PFTs after inhalers

  31. Inhalers - β agonists • Short acting – salbutamol • Long acting –salmeterol • Mechanism • Stimulates β receptors • Dilates bronchioles, easier breathing • Side effects • Also stimulates heart’s β receptors – tachycardia, hypertension

  32. Inhalers – ipratropium • AKA Atrovent • Mechanism • Anticholinergic drug – blocks muscarinic receptors • Prevents smooth muscle contraction • Widens the airways • Side effects • Can induce AF & tachycardia

  33. Inhalers – steroids • Fluticasone, beclometasone • Action of glucocorticoid steroids unknown in asthma • May inhibit part of the inflammatory process involved in the asthmatic response • Not for treatment, but prevention • Hence given twice daily, regularly

  34. Inhalers – combinations • Some drugs more effective if given simultaneously (synergy) • Seretide • Salmeterol & fluticasone • Combivent • Ipratropium & salbutamol