Prescibing analgesics

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Prescibing analgesics

  1. 1. Prescribing Analgesics www.freelivedoctor.com
  2. 2. <ul><li>Non-opioid analgesics </li></ul><ul><li>Opioid analgesics </li></ul><ul><li>Drugs for neuropathic and functional pain </li></ul><ul><li>Antimigraine drugs </li></ul>Analgesics www.freelivedoctor.com
  3. 3. <ul><li>Acetaminophen (paracetamol) </li></ul><ul><li>NSAIDs – non selective </li></ul><ul><ul><ul><ul><ul><li>- Selective Cox 2 inhibitors </li></ul></ul></ul></ul></ul>Nonopioid analgesics www.freelivedoctor.com
  4. 4. PARACETAMOL ( acetaminophen) <ul><li>equivalent analgesic efficacy to aspirin </li></ul><ul><li>no useful anti-inflammatory action </li></ul><ul><li>used for mild to moderate pain, but aspirin is preferred if due to inflammatory process </li></ul>www.freelivedoctor.com
  5. 5. PARACETAMOL ( acetaminophen) <ul><li>Metabolism </li></ul><ul><li>is conjugated in the liver as the inactive glucuronide and sulphate </li></ul><ul><li>a number of minor oxidation products inc. </li></ul><ul><li>N-acetylbenzoquinoneimine (NABQI) are also formed </li></ul><ul><li>NABQI is highly chemically reactive and is usually inactivated by conjugation with SH (thiol) groups of glutathione </li></ul><ul><li>Supply of glutathione is limited and exhausted in overdose </li></ul><ul><li>NABQI then reacts with cellular macromolecules and causes cell death </li></ul>www.freelivedoctor.com
  6. 6. PARACETAMOL ( acetaminophen) <ul><li>Adverse effects </li></ul><ul><li>rare in therapeutic usage </li></ul><ul><li>occasional skin rash and allergy </li></ul><ul><li>Overdose can result in fulminant hepatic necrosis and liver failure </li></ul>www.freelivedoctor.com
  7. 7. PARACETAMOL ( acetaminophen) <ul><li>Paracetamol overdose </li></ul><ul><li>Ingestion of >10g of paracetamol may be fatal </li></ul><ul><li>may be lower in chronic alcoholics or subjects with underlying liver disease. </li></ul><ul><li>Clinical features </li></ul><ul><li>In severe poisoning </li></ul><ul><li>up to 24 hours - none or nausea and vomiting </li></ul><ul><li>> 24 hours - nausea and vomiting, right upper quadrant pain, jaundice, encephalopathy </li></ul>www.freelivedoctor.com
  8. 8. PARACETAMOL ( acetaminophen) <ul><li>Management </li></ul><ul><li>Blood for paracetamol at 4 hours post ingestion </li></ul><ul><li>Check treatment curve for N-acetylcysteine infusion ( if in doubt of severe poisoning, don’t delay) </li></ul><ul><li>Check prothrombin time and plasma creatinine , pH </li></ul><ul><li>acute renal (due to acute tubular necrosis) and hepatic failure and occur at 36-72 hours after ingestion </li></ul><ul><li>Indications for referral to liver unit are </li></ul><ul><li>- rapid development of Grade 2 encephalopathy </li></ul><ul><li>- PTT >45 secs at 48 hours or >50 secs at 72 hours </li></ul><ul><li>- rising plasma creatinine </li></ul><ul><li>- Arterial pH <7.3 more than 24 hours after ingestion </li></ul>www.freelivedoctor.com
  9. 9. NSAIDs <ul><li>Mechanism of action </li></ul><ul><li>inhibits cyclo-oxygenase (prostaglandin synthase) that is responsible for conversion of arachidonic acid to cyclic endoperoxides </li></ul><ul><li>2 isoforms of enzyme </li></ul><ul><li>- COX-1 constitutive, present in platelets, </li></ul><ul><li>stomach and kidney </li></ul><ul><li>- COX-2 inducible by cytokines & endotoxins at sites of inflammation e.g., joints </li></ul>www.freelivedoctor.com
  10. 10. NSAIDs <ul><li>Main actions </li></ul><ul><li>1.) Analgesic -effective against mild to moderate pain, do not cause dependence </li></ul><ul><li>2.) Anti-inflammatory </li></ul><ul><li>3.) Anti-pyretic </li></ul><ul><li>4.)Anti-platelet- prevent thromboxane production, derived from prostaglandins and cause platelet aggregation </li></ul><ul><li>Others </li></ul><ul><li>5.) Useful in treatment of dysmenorrhea, associated with increased prostaglandin synthesis and increased uterine contractility </li></ul><ul><li>6.) Used to close the patent ductus arteriosus </li></ul>www.freelivedoctor.com
  11. 11. NSAIDs <ul><li>Adverse effects </li></ul><ul><li>1.) Gastric or intestinal mucosal damage </li></ul><ul><li>- mucosal prostaglandins inhibit acid secretion, promote mucus </li></ul><ul><li>secretion, prevent back diffusion of acid into the gastric submucosa </li></ul><ul><li>- Inhibition thus results in erosions, ulceration, bleeding, perforation </li></ul><ul><li>2.) Disturbances of fluid and electrolyte balance </li></ul><ul><li>- inhibition of renal prostaglandin production results in sodium retention and oedema, possible hyponatraemia, hyperkalaemia, antagonism of anti-hypertensive agents </li></ul><ul><li>3.) Analgesic nephropathy </li></ul><ul><li>- due to long term ingestion of mixtures of agents </li></ul><ul><li>- chronic interstitial nephritis, renal papillary necrosis, acute renal </li></ul><ul><li> failure </li></ul>www.freelivedoctor.com
  12. 12. NSAIDs <ul><li>Non selective Vs selective COX2 inhibitors </li></ul><ul><li>↑ risk of cardiovascular adverse events with COX 2 inhibitors </li></ul><ul><li>Rofecoxib was withdrawn from the market </li></ul><ul><li>Higher BP, incidence of myocardial infarction, stroke </li></ul><ul><li>Mechanism _ ? Unopposed effect of cox 1 action </li></ul><ul><li> - ? Block protective effect of COX2 on </li></ul><ul><li> ishaemic myocardium or atherogenesis </li></ul>www.freelivedoctor.com
  13. 13. NSAIDs <ul><li>Classifications </li></ul><ul><li>Mild to moderate anti-inflammatory action </li></ul><ul><li>- propionic acid derivatives ibuprofen, naproxen </li></ul><ul><li>- fenamic acids mefanamic acid </li></ul><ul><li>Marked anti-inflammatory action </li></ul><ul><li>- salicylic acids aspirin </li></ul><ul><li>- pyrazolone derivatives azapropazone, phenylbutazone </li></ul><ul><li>- acetic acid derivatives diclofenac, indomethacin </li></ul><ul><li>- oxicam derivatives piroxicam </li></ul><ul><li>Selective COX2 inhibitors celecoxib, rofecoxib </li></ul>www.freelivedoctor.com
  14. 14. Aspirin (acetyl salicylate) <ul><li>Actions </li></ul><ul><li>Analgesic - central and peripheral action </li></ul><ul><li>Antipyretic - act in hypothalamus to lower the set point of temperature control elevated by fever, </li></ul><ul><li> also causes sweating </li></ul><ul><li>anti-inflammatory - inhibition of peripheral prostaglandin synthesis </li></ul><ul><li>respiratory stimulation - direct action on respiratory centre, indirectly by ↑ CO2 production </li></ul>www.freelivedoctor.com
  15. 15. Aspirin (acetyl salicylate) <ul><li>Metabolic effects </li></ul><ul><li>i.) ↑ peripheral O 2 consumption (uncoupled oxidative phosphorylation) hence ↑CO2 production with ↑ respiration, and direct analeptic action - respiratory alkalosis </li></ul><ul><li>ii) renal loss of bicarbonate with sodium, potassium and water </li></ul><ul><li>iii) dehydration </li></ul><ul><li>iv) metabolic acidosis - effects on Krebs cycle, ↑ ketone body, salicylic acid in blood, renal insufficiency due to vascular collapse, dehydration </li></ul><ul><li>v) hypoglycaemia or even hyperglycaemia can occur </li></ul>www.freelivedoctor.com
  16. 16. Aspirin (acetyl salicylate) <ul><li>Uricosuric effects </li></ul><ul><li>reduces renal tubular reabsorption of urate but treatment of gout requires 5-8g/d, < 2g/d may cause retention of urate. </li></ul><ul><li>antagonises the uricosuric action of other drugs </li></ul><ul><li>Reduced platelet adhesion- irreversible inhibition of COX by acetylation, prolongs bleeding time, useful in arterial disease </li></ul><ul><li>Note: low doses are adequate for this purpose since the platelet has no biosynthetic capacity and can not regenerate the enzyme </li></ul><ul><li>Hypothrombinaemia : occurs with large doses ie >5g/day </li></ul>www.freelivedoctor.com
  17. 17. Aspirin (acetyl salicylate) <ul><li>OVERDOSAGE </li></ul><ul><li>Ingestion of > 10 g can cause moderate/severe poisoning in an adult </li></ul><ul><li>Clinical features - ‘salicylism’ </li></ul><ul><li>tremor, tinnitus, hyperventilation, nausea, vomiting, sweating </li></ul><ul><li>Management- mainly supportive </li></ul>www.freelivedoctor.com
  18. 18. OPIATE ANALGESICS <ul><li>Classification </li></ul><ul><li>Low efficacy Codeine </li></ul><ul><li>Dihydrocodeine </li></ul><ul><li>Dextropropoxyphene (coproxamol- withdrawn from market) </li></ul><ul><li>Medium efficacy Bupranorphine </li></ul><ul><li>meptazinol </li></ul><ul><li>High efficacy Morphine </li></ul><ul><li>Diamorphine </li></ul><ul><li>pethidine </li></ul>www.freelivedoctor.com
  19. 19. OPIATE ANALGESICS <ul><li>Routes of administration </li></ul><ul><li>Oral </li></ul><ul><li>Parenteral </li></ul><ul><li>Suppositories </li></ul><ul><li>Transdermal- Patch </li></ul><ul><li>s/c Syringe driver </li></ul>www.freelivedoctor.com
  20. 20. OPIATE ANALGESICS <ul><li>Mechanism of action </li></ul><ul><li>Bind to CNS opioid receptors whose natural ligands are endorphins and encephalins. </li></ul>www.freelivedoctor.com
  21. 21. OPIATE ANALGESICS <ul><li>Actions </li></ul><ul><li>CNS </li></ul><ul><li>Depression Stimulation </li></ul><ul><li>Analgesia vomiting </li></ul><ul><li>Respiratory depression miosis </li></ul><ul><li>Depression of cough reflex ↑ spinal reflexes </li></ul><ul><li>sleep (convulsions) </li></ul><ul><li>mood changes- Euphoria </li></ul><ul><li>Dependence – also affects other systems </li></ul>www.freelivedoctor.com
  22. 22. OPIATE ANALGESICS <ul><li>Smooth muscle stimulation </li></ul><ul><li>GI muscle spasm causing delayed transit and constipation </li></ul><ul><li>Biliary spasm </li></ul><ul><li>Bronchospasm </li></ul><ul><li>Cardiovascular </li></ul><ul><li>Dilation of resistance vessels (arterioles) and capacitance vessels (veins) </li></ul>www.freelivedoctor.com
  23. 23. OPIATE ANALGESICS <ul><li>Smooth muscle stimulation </li></ul><ul><li>GI muscle spasm causing delayed transit and constipation </li></ul><ul><li>Biliary spasm </li></ul><ul><li>Bronchospasm </li></ul><ul><li>Cardiovascular </li></ul><ul><li>Dilation of resistance vessels (arterioles) and capacitance vessels (veins) </li></ul><ul><li>Hazards of Clinical Use </li></ul><ul><li>Respiratory depression </li></ul><ul><li>Retention in hepatic and renal impairment </li></ul><ul><li>Dependence </li></ul>www.freelivedoctor.com
  24. 24. OPIATE ANALGESICS <ul><li>Dependence </li></ul><ul><li>Up to 8 h- Mild psychological withdrawal stress </li></ul><ul><li>8-12 h - increasing nervousness, restlessness and anxiety </li></ul><ul><li>12-24h - yawning, sweating, runny eyes and nose </li></ul><ul><li>24 h - pupils dilate, waves of goose flesh </li></ul><ul><li>36 h - twitching of muscles, leg & abdominal cramps </li></ul><ul><li> vomiting and diarrhoea and anorexia, insomnia </li></ul><ul><li> tachypnoea, ↑ BMR and mild pyrexia </li></ul><ul><li>48-72 h - peak withdrawal symptoms </li></ul><ul><li>up to 10 d- symptoms gradually subside </li></ul><ul><li>Complete recovery requires 3-6 months </li></ul><ul><li>Note : Withdrawal syndrome can be in part alleviated by long acting opioid such as methadone </li></ul><ul><li>Reduction of rebound sympathetic activity with clonidine may be needed </li></ul>www.freelivedoctor.com
  25. 25. OPIATE ANALGESICS <ul><li>Opioid overdose </li></ul><ul><li>Death usually due to respiratory depression </li></ul><ul><li>Cardiovascular function usually well preserved unless severe anoxia </li></ul><ul><li>Treatment with iv naloxone </li></ul><ul><li>May need infusion - naloxone has shorter t 1/2 (1h), particularly for opioids with long t 1/2 – (methadone) and tight binding (bupranorphine) </li></ul>www.freelivedoctor.com
  26. 26. <ul><li>Mild pain </li></ul><ul><li>Non-opioid analgesics paracetamol </li></ul><ul><li>NSAIDs aspirin, ibuprofen </li></ul><ul><li>Moderate pain </li></ul><ul><li>1. Low efficacy opioid dihydrocodeine </li></ul><ul><li>2. low efficacy opioid + NSAID dihydrocodeine + ibuprofen </li></ul><ul><li>3. Moderate efficacy opioid + NSAID meptazinol + ibuprofen </li></ul><ul><li>Severe pain </li></ul><ul><li>1. High efficacy opioids morphine </li></ul><ul><li>2. High efficacy opioids + NSAIDS morphine + ibuprofen </li></ul><ul><li>Overwhelming pain </li></ul><ul><li>1. High efficacy opioid + anxiolytic morphine + diazepam </li></ul><ul><li> and/or major tranquilliser morphine + chlorpromazine </li></ul>Overall Management of Pain www.freelivedoctor.com
  27. 27. <ul><li>Keep it simple </li></ul><ul><li>Become familiar with a couple of agents from each class. If in doubt, check in BNF </li></ul><ul><li>Familiarise with used of control drug (opioid) </li></ul><ul><li>Identify and treat the underlying pathology wherever possible </li></ul><ul><li>Be careful with potential overdoses and dependency </li></ul><ul><li>Explanation and reassurance contribute greatly to analgesia </li></ul>Messages www.freelivedoctor.com

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