Clinical Pharmacology

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Clinical Pharmacology

• Prescribing
• October 2005
• Dr Joseph Cheriyan
• Dr Fraz Mir

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Why use drugs?

• To improve quality or quantity of life
• To cure, suppress or prevent disease

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Before starting treatment !

• Decide whether a drug is necessary. If it is
• 1. What are you hoping to achieve?
• 2. Will the drug chosen will bring this about?
• 3. What other effects the drug might have
  could these be harmful?
• 4. Does benefit outweigh risk?

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Risk versus benefit

• Negligible risk
• Acceptable risk
• Unacceptable risk

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How should you choose a drug?

• Safety tolerability
• Efficacy
• Cost-effectiveness

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Why take a drug history?
Drugs

• can cause disease (early or late)
• can conceal disease
• can give diagnostic clues
• can interfere with diagnostic tests
• history can assist treatment choice

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History of adverse reactions?

• I cant take antibiotics, they make me ill,
  doctor
• Which specific drugs?
• When?
• Actual adverse reaction, beware allergy
• Similar drugs since?

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Reporting of adverse drug reactions

• Yellow card system
• All suspected reactions to new drugs
• Serious reactions to established drugs
• Committee on Safety of Medicines (CSM)
• Medicines and Healthcare Devices Regulatory
  Authority (MHRA)

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Responsibilities of the physician?

• Not to be ignorant of existing knowledge or
  important new developments
• To adopt new developments of proven value
• To prescribe accurately and clearly
• To avoid inappropriate prescribing
• To tell patients what they need to know
• To accept responsibility for ones actions

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What should you tell the patient (1)?

• About the condition and why we are treating it
• The name of the medicine
• It may help to write this down for the patient
• The objective of the treatment
• Whether and how the patient will judge benefit
• How soon benefit can be expected

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What should we tell the patient (2) ?

• How and when to take the medicine
• What to do about a missed dose
• How long the medicine is likely to be needed
• How to recognise ADRs and how to respond to them
• Important interactions with e.g. alcohol and
  other medicines

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The prescription pitfalls

• Doses
• Route
• Choose an appropriate route e.g. is the patient
  vomiting?
• Care with doses with different routes e.g.
  Penicillin 1.2g iv versus 1.2mg intrathecal
• Do not use the im route if patient is
  anticoagulated

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The prescription pitfalls

• Doses
• Vancomycin
• Cl difficile 125mg qds PO
• Staph aureus 1g bd IV

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The prescription pitfalls

• Doses
• Dose reduction
• Elderly, renal failure, hepatic failure
• Children
• Dose often calculated by weight
• Paediatric pharmacopoeia available

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The prescription pitfalls

• Rate
• Bolus vs Infusion
• Vancomycin red man syndrome
• Frusemide and ototoxicity
• Minutes or hours
• ml or mg
• GTN 50mg in 50ml (5 dextrose) at 1 to 10 ml per
  hour

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The prescription pitfalls

• Cost
• Cl Difficile
• Metronidazole 1-50
• Vancomycin 105-00

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Contra-indications

• Absolute
• Beta blockers and asthma
• Misoprostol and pregnancy
• Relative
• Ciprofloxacin and epilepsy

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Interactions

• Two drugs together
• Beta blockers (IV or PO) and verapamil (IV)
• Phenytoin and the OCP
• Ciprofloxacin and theophylline
• Enzyme inducers vs. enzyme inhibitors
• Nutrition
• NG feeding and phenytoin
• Diseases
• Ampicillin and EBV

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Special situations

• Pregnancy
• Avoid all drugs if possible but especially
  ACEI, gentamicin, carbimazole, isotretinoin,
  misoprostol
• Breast feeding
• Avoid most drugs especially ciprofloxacin,
  amiodarone
• Renal / Hepatic impairment
• Avoidance, or change in dose gentamicin,
  opiates

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How can we contain cost?

• Appropriate prescribing
• Generic prescribing
• Therapeutic substitution
• Timely discontinuation
• However, many patients do not receive treatment
  from which they would clearly benefit (e.g. in
  hyperlipidaemia and heart failure)

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Compliance

• Also adherence / concordance / co-operation
• 25-50 of patients take lt 90 of prescribed dose
• May be due to poor understanding, so cannot
  comply
• Can occur in the face of good understanding

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Main reasons for poor compliance

• Poor doctor-patient relationship
• Lack of motivation
• Forgetfulness
• Deliberate intention
• Lack of information
• Frequency complexity of drug regimen (and
  total number of drugs)
• Adverse drug reactions

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How can we improve compliance?

• Form a partnership with the patient
• Provide oral and written information
• Rationalise drug therapy
• Plan treatment around the patients life
• Use patient-friendly packaging
• Use combined fixed-dose SR formulations
• See the patient regularly
• Use dosette box if appropriate

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Summary

• Prescribing is an important responsibility
• Potential to do harm as well as good
• Good prescribing is fundamental to being a good
  doctor

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• Poisons in small doses are the best medicines
  and useful medicines in too large doses are
  poisonous
• William Withering 1789

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Drug Calculations and Prescriptions
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Question 1

• 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.
• A) what important feature in the history do
  you have to elicit before this?
• 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
• Prescribe this on the infusion chart. Write
  out a prescription for the nurses to begin this
  emergency drug.

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Answer

• a) Check not on oral Theophylline. If so do not
  give a loading dose and check plasma theophylline
  levels.
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• b) Loading 300mg bolus over at least 20 minutes.
  Written on yellow infusion chart as
• Date 21/10/5 Line IV Type of fluid 5 dextrose
  or 0.9 Saline
• Additives Aminophylline 300mg Volume 100 ml
  Rate over 20 mins.
• SIGN!!
• Maintenance 30mg/hour. Written on yellow
  infusion chart as
• Date 21/10/5 Line IV Type of fluid 5
  dextrose or 0.9 saline
• Additives Aminophylline 500mg Volume 500ml
  Rate 30ml/hour
• SIGN!!
• or 500mg in 250 ml dextrose/saline at a rate of
  15ml/hour.

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Question 2

• A young man has fallen down and sustained a
  laceration to his head. He presents to AE 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
• What is the maximum dose in mls?
• Write out a prescription for this on the
  appropriate chart

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Answer

• 2 lidocaine 2g in 100 ml
• 2000mg in 100ml
• 20 mg in 1 ml
• Max dose is 200mg (in solutions with Adrenaline
  max dose is 500mg) hence maximum volume is 10ml.
• Write out on once only prescription chart as
• Date 21/10/2005 Drug Lidocaine 2 Dose 200mg
• Route S/C Time as and when given
• and SIGN!!

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Answer Once Only side of Prescription Card
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Question 3

• 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.
• 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.

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Answer

• 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
• Date 21/10/05 Line IV Type of fluid
  Saline 0.9 Additives Phenytoin 1200mg
  Volume 200ml Rate 8ml/min SIGN!!
• or 1000 mg in 100ml saline (10mg/ml) at 5ml/min
  followed by
• 200mg in 20 ml saline at
  5ml/min.
• total 1200mg
• Maintenance 100mg tds or qds IV in 100 ml
  n/saline
• Drug Phenytoin Dose 100mg Route IV
  Start Date 21/10/2005 Circle frequencies eg
  8,14,22
• Additional Instructions in 100 ml saline
  SIGN!!!

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Parenteral Infusion Chart
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Maintenance dosing Prescription Chart
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Question 4

• 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.

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Answer

• N-Acetyl 7500mg in 200ml 5glu over 15 mins
  then
• 2500mg in 500ml over 4
  hours then
• 5000mg in 1000ml over 16
  hours
• Write out on yellow infusion card as
• Date 7/11/3 Line IV
• Type of fluid Additives
  Vol Rate
• 5 dextrose N-Acetlycysteine
  7500mg 200ml over 15 minutes
• 5 dextrose N-Acetylcysteine
  2500mg 500ml over 4 hours
• 5 dextrose N-Acetylcysteine
  5000mg 1 litre over 16 hours
• And SIGN!!

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Parenteral Infusion Card
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Question 5

• 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.
• The BNF suggests 10mg/kg every 8 hours for
  simplex encephalitis

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Answer

• 650mg Aciclovir in 150 or 200 ml saline/glucose
  (ie 5mg/ml or less) tds over 1 hour for total
  10 days
• On regular drug card
• Drug Aciclovir
• Dose 650mg
• Route IV
• Start Date 21/10/05
• Additional instr in 200 ml saline 0.9
• Freq Circle 8,14,22
• SIGN!!

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Maintenance - Prescription Chart
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Further resources

• ER-WEB further information on prescribing
• http//erweb.cbu.cam.ac.uk/?1523
• Clinical Pharmacology Unit Lecture Slides
  further drug calculations
• http//www-clinpharm.medschl.cam.ac.uk/