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  1. 1. Clinical Pharmacology
  2. 2. Why use drugs? <ul><li>To improve quality or quantity of life </li></ul><ul><li>To cure , suppress or prevent disease </li></ul>
  3. 3. Before starting treatment ! <ul><li>Decide whether a drug is necessary. If it is: </li></ul><ul><li>1. What are you hoping to achieve? </li></ul><ul><li>2. Will the drug chosen will bring this about? </li></ul><ul><li>3. What other effects the drug might have – could these be harmful? </li></ul><ul><li>4. Does benefit outweigh risk? </li></ul>
  4. 4. Risk versus benefit <ul><li>Negligible risk </li></ul><ul><li>Acceptable risk </li></ul><ul><li>Unacceptable risk </li></ul>
  5. 5. How should you choose a drug? <ul><li>Safety & tolerability </li></ul><ul><li>Efficacy </li></ul><ul><li>Cost-effectiveness </li></ul>
  6. 6. Why take a drug history? <ul><li>can cause disease (early or late) </li></ul><ul><li>can conceal disease </li></ul><ul><li>can give diagnostic clues </li></ul><ul><li>can interfere with diagnostic tests </li></ul><ul><li>history can assist treatment choice </li></ul>Drugs:
  7. 7. History of adverse reactions? <ul><li>“ I can’t take antibiotics, they make me ill, doctor” </li></ul><ul><li>Which specific drugs? </li></ul><ul><li>When? </li></ul><ul><li>Actual adverse reaction, beware “allergy” </li></ul><ul><li>Similar drugs since? </li></ul>
  8. 8. Reporting of adverse drug reactions <ul><li>Yellow card system </li></ul><ul><li>All suspected reactions to new drugs </li></ul><ul><li>Serious reactions to established drugs </li></ul><ul><li>Committee on Safety of Medicines (CSM) </li></ul><ul><li>Medicines and Healthcare Devices Regulatory Authority (MHRA) </li></ul>
  9. 11. Responsibilities of the physician? <ul><li>Not to be ignorant of existing knowledge or important new developments </li></ul><ul><li>To adopt new developments of proven value </li></ul><ul><li>To prescribe accurately and clearly </li></ul><ul><li>To avoid inappropriate prescribing </li></ul><ul><li>To tell patients what they need to know </li></ul><ul><li>To accept responsibility for one’s actions </li></ul>
  10. 12. What should you tell the patient (1)? <ul><li>About the condition and why we are treating it </li></ul><ul><li>The name of the medicine </li></ul><ul><ul><li>It may help to write this down for the patient </li></ul></ul><ul><li>The objective of the treatment </li></ul><ul><li>Whether and how the patient will judge benefit </li></ul><ul><li>How soon benefit can be expected </li></ul>
  11. 13. What should we tell the patient (2) ? <ul><li>How and when to take the medicine </li></ul><ul><li>What to do about a missed dose </li></ul><ul><li>How long the medicine is likely to be needed </li></ul><ul><li>How to recognise ADRs and how to respond to them </li></ul><ul><li>Important interactions with e.g. alcohol and other medicines </li></ul>
  12. 14. The prescription – pitfalls <ul><li>Doses </li></ul><ul><li>Route </li></ul><ul><ul><li>Choose an appropriate route e.g. is the patient vomiting? </li></ul></ul><ul><ul><li>Care with doses with different routes e.g. Penicillin 1.2 g iv versus 1.2mg intrathecal </li></ul></ul><ul><ul><li>Do not use the im route if patient is anticoagulated </li></ul></ul>
  13. 15. The prescription – pitfalls <ul><li>Doses </li></ul><ul><li>Vancomycin </li></ul><ul><ul><li>Cl difficile 125mg qds PO </li></ul></ul><ul><ul><li>Staph aureus 1g bd IV </li></ul></ul>
  14. 16. The prescription – pitfalls <ul><li>Doses </li></ul><ul><li>Dose reduction </li></ul><ul><ul><li>Elderly, renal failure, hepatic failure </li></ul></ul><ul><li>Children </li></ul><ul><ul><li>Dose often calculated by weight </li></ul></ul><ul><ul><li>Paediatric pharmacopoeia available </li></ul></ul>
  15. 17. The prescription – pitfalls <ul><li>Rate </li></ul><ul><li>Bolus vs Infusion </li></ul><ul><ul><li>Vancomycin “red man syndrome” </li></ul></ul><ul><ul><li>Frusemide and ototoxicity </li></ul></ul><ul><li>Minutes or hours </li></ul><ul><li>ml or mg </li></ul><ul><ul><li>GTN 50mg in 50ml (5% dextrose) at 1 to 10 ml per hour </li></ul></ul>
  16. 18. The prescription – pitfalls <ul><li>Cost </li></ul><ul><li>Cl Difficile </li></ul><ul><ul><li>Metronidazole £1-50 </li></ul></ul><ul><ul><li>Vancomycin £105-00 </li></ul></ul>
  17. 19. Contra-indications <ul><li>Absolute </li></ul><ul><ul><li>Beta blockers and asthma </li></ul></ul><ul><ul><li>Misoprostol and pregnancy </li></ul></ul><ul><li>Relative </li></ul><ul><ul><li>Ciprofloxacin and epilepsy </li></ul></ul>
  18. 20. Interactions <ul><li>Two drugs together </li></ul><ul><ul><li>Beta blockers (IV or PO) and verapamil (IV) </li></ul></ul><ul><ul><li>Phenytoin and the OCP </li></ul></ul><ul><ul><li>Ciprofloxacin and theophylline </li></ul></ul><ul><ul><li>Enzyme inducers vs. enzyme inhibitors </li></ul></ul><ul><li>Nutrition </li></ul><ul><ul><li>NG feeding and phenytoin </li></ul></ul><ul><li>Diseases </li></ul><ul><ul><li>Ampicillin and EBV </li></ul></ul>
  19. 21. Special situations <ul><li>Pregnancy </li></ul><ul><ul><li>Avoid all drugs if possible – but especially ACEI, gentamicin, carbimazole, isotretinoin, misoprostol </li></ul></ul><ul><li>Breast feeding </li></ul><ul><ul><li>Avoid most drugs – especially ciprofloxacin, amiodarone </li></ul></ul><ul><li>Renal / Hepatic impairment </li></ul><ul><ul><li>Avoidance, or change in dose – gentamicin, opiates </li></ul></ul>
  20. 22. How can we contain cost? <ul><li>Appropriate prescribing </li></ul><ul><li>Generic prescribing </li></ul><ul><li>Therapeutic substitution </li></ul><ul><li>Timely discontinuation </li></ul><ul><li>However , many patients do not receive treatment from which they would clearly benefit (e.g. in hyperlipidaemia and heart failure) </li></ul>
  21. 23. Compliance <ul><li>Also: adherence / concordance / co-operation </li></ul><ul><li>25-50% of patients take < 90% of prescribed dose </li></ul><ul><li>May be due to poor understanding, so cannot comply </li></ul><ul><li>Can occur in the face of good understanding </li></ul>
  22. 24. Main reasons for poor compliance <ul><li>Poor doctor-patient relationship </li></ul><ul><li>Lack of motivation </li></ul><ul><li>Forgetfulness </li></ul><ul><li>Deliberate intention </li></ul><ul><li>Lack of information </li></ul><ul><li>Frequency & complexity of drug regimen (and total number of drugs) </li></ul><ul><li>Adverse drug reactions </li></ul>
  23. 25. How can we improve compliance? <ul><li>Form a ‘partnership’ with the patient </li></ul><ul><li>Provide oral and written information </li></ul><ul><li>Rationalise drug therapy </li></ul><ul><li>Plan treatment around the patient’s life </li></ul><ul><li>Use ‘patient-friendly’ packaging </li></ul><ul><li>Use combined fixed-dose & SR formulations </li></ul><ul><li>See the patient regularly </li></ul><ul><li>Use dosette box if appropriate </li></ul>
  24. 29. Summary <ul><li>Prescribing is an important responsibility </li></ul><ul><li>Potential to do harm as well as good </li></ul><ul><li>Good prescribing is fundamental to being a good doctor </li></ul>
  25. 30. <ul><li>“ Poisons in small doses are the best medicines; and useful medicines in too large doses are poisonous” </li></ul><ul><li>William Withering 1789 </li></ul>
  26. 31. Drug Calculations and Prescriptions
  27. 32. Question 1 <ul><li>An asthmatic presents with a severe exacerbation of asthma. She has had a dose of steroid, high flow oxygen and has had a few nebules of Salbutamol and Atrovent. However, her peak flow is still very low and she remains tachypnoeic. You are the admitting doctor and after review by your senior, you are asked to prescribe intravenous Aminophylline. </li></ul><ul><li>A) what important feature in the history do you have to elicit before this? </li></ul><ul><li>B) her weight is 60kg – BNF dose is 5mg/kg loading given over 20 minutes and 500 microg/kg/hour maintenance dose in saline or 5% dextrose </li></ul><ul><li>Prescribe this on the infusion chart. Write out a prescription for the nurses to begin this emergency drug. </li></ul>
  28. 33. Answer <ul><li>a) Check not on oral Theophylline. If so do not give a loading dose and check plasma theophylline levels. </li></ul><ul><li>  </li></ul><ul><li>b) Loading 300mg bolus over at least 20 minutes. Written on yellow infusion chart as: </li></ul><ul><li>Date : 21/10/5 Line : IV Type of fluid : 5% dextrose or 0.9% Saline </li></ul><ul><li>Additives : Aminophylline 300mg Volume : 100 ml Rate : over 20 mins. </li></ul><ul><li>SIGN!! </li></ul><ul><li>Maintenance = 30mg/hour. Written on yellow infusion chart as: </li></ul><ul><li>Date: 21/10/5 Line : IV Type of fluid: 5% dextrose or 0.9% saline </li></ul><ul><li>Additives : Aminophylline 500mg Volume: 500ml Rate : 30ml/hour </li></ul><ul><li>SIGN!! </li></ul><ul><li>or 500mg in 250 ml dextrose/saline at a rate of 15ml/hour. </li></ul>
  29. 35. Question 2 <ul><li>A young man has fallen down and sustained a laceration to his head. He presents to A&E and has a wound that will require suturing under local anaesthetic. The Sister hands you a box of vials of Lidocaine 2%. The patient weighs 70kg. Work out the maximum volume of lidocaine 2% you can use as a local anaesthetic in this patient. – BNF recommends a maximum dose of 200mg in any patient </li></ul><ul><li>What is the maximum dose in mls? </li></ul><ul><li>Write out a prescription for this on the appropriate chart </li></ul>
  30. 36. Answer <ul><li>2% lidocaine = 2g in 100 ml </li></ul><ul><li>= 2000mg in 100ml </li></ul><ul><li>= 20 mg in 1 ml </li></ul><ul><li>Max dose is 200mg (in solutions with Adrenaline – max dose is 500mg) hence maximum volume is 10ml. </li></ul><ul><li>Write out on once only prescription chart as: </li></ul><ul><li>Date: 21/10/2005 Drug: Lidocaine 2% Dose : 200mg </li></ul><ul><li>Route: S/C Time: as and when given </li></ul><ul><li>and SIGN!! </li></ul>
  31. 37. Answer – Once Only side of Prescription Card
  32. 38. Question 3 <ul><li>An elderly man with known epilepsy presents in status epilepticus. He has already had rectal and intravenous Diazepam but these have failed to settle his convulsions. After review by the on call SpR, a decision is made to write him up for intravenous Phenytoin – loading then maintenance dose. The BNF states: For IV infusion (use saline 0.9%) in status epilepticus 15mg/kg at a rate not exceeding 50mg/minute as a loading dose; maintenance doses of about 100mg thereafter at intervals of 6 – 8 hours. Work out the correct infusion rates for the loading and maintenance doses. </li></ul><ul><li>Write up an infusion of Phenytoin on the infusion chart. The patient weighs 80kg. Also write up the regular maintenance dose on the appropriate drug card. </li></ul>
  33. 39. Answer <ul><li>Loading = 1200mg. (80kg x 15mg/kg). Admin rate not more than 50mg/min hence write as: eg: 1200 mg Phenytoin in 200 ml saline 0.9% (= 6mg/ml) at a rate of 8ml/min </li></ul><ul><li>Date : 21/10/05 Line : IV Type of fluid : Saline 0.9% Additives: Phenytoin 1200mg Volume: 200ml Rate: 8ml/min SIGN!! </li></ul><ul><li>or 1000 mg in 100ml saline (=10mg/ml) at 5ml/min followed by </li></ul><ul><ul><li>200mg in 20 ml saline “ “ at 5ml/min. </li></ul></ul><ul><ul><li>= total 1200mg </li></ul></ul><ul><li>Maintenance = 100mg tds or qds IV in 100 ml n/saline </li></ul><ul><li>Drug: Phenytoin Dose: 100mg Route : IV Start Date : 21/10/2005 Circle frequencies eg 8,14,22 </li></ul><ul><li>Additional Instructions : in 100 ml saline SIGN!!! </li></ul>
  34. 40. Parenteral Infusion Chart
  35. 41. Maintenance dosing – Prescription Chart
  36. 42. Question 4 <ul><li>A young girl (weight 50kg) has taken 30 tablets of Paracetamol 500mg. She is brought into casualty 8 hours after the overdose. She admits to taking the overdose with alcohol. Her paracetamol levels indicate that she is at high risk of hepatocellular necrosis so the Regional Poisons Unit advises you to commence an infusion regime of N-Acetylcysteine (Parvolex). The BNF states for IV infusion in 5% glucose, initially 150mg/kg in 200 ml over 15 mins, followed by 50mg/kg in 500ml over 4 hours then 100mg/kg in 1000ml over 16 hours. </li></ul>
  37. 43. Answer <ul><li>N-Acetyl 7500mg in 200ml 5%glu over 15 mins then </li></ul><ul><li>2500mg in 500ml over 4 hours then </li></ul><ul><li>5000mg in 1000ml over 16 hours </li></ul><ul><li>Write out on yellow infusion card as: </li></ul><ul><li>Date : 7/11/3 Line : IV </li></ul><ul><li>Type of fluid Additives Vol Rate </li></ul><ul><li>5% dextrose N-Acetlycysteine 7500mg 200ml over 15 minutes </li></ul><ul><li>5% dextrose N-Acetylcysteine 2500mg 500ml over 4 hours </li></ul><ul><li>5% dextrose N-Acetylcysteine 5000mg 1 litre over 16 hours </li></ul><ul><li>And SIGN!! </li></ul>
  38. 44. Parenteral Infusion Card
  39. 45. Question 5 <ul><li>An elderly lady presents with confusion, fits and altered behaviour associated with a low grade pyrexia. Further investigations go on to reveal she has herpes encephalitis. The decision is made to start intravenous Acyclovir. Work out the dose for this 65kg woman and write out a prescription on the drug card. </li></ul><ul><li>The BNF suggests 10mg/kg every 8 hours for simplex encephalitis </li></ul>
  40. 46. Answer <ul><li>650mg Aciclovir in 150 or 200 ml saline/glucose (ie 5mg/ml or less) tds over 1 hour for total 10 days </li></ul><ul><li>On regular drug card: </li></ul><ul><li>Drug: Aciclovir </li></ul><ul><li>Dose: 650mg </li></ul><ul><li>Route: IV </li></ul><ul><li>Start Date: 21/10/05 </li></ul><ul><li>Additional instr: in 200 ml saline 0.9% </li></ul><ul><li>Freq: Circle 8,14,22 </li></ul><ul><li>SIGN!! </li></ul>
  41. 47. Maintenance - Prescription Chart