Transcript clinical pharmacology-1

Clinical Pharmacology
Prescribing
November 2003
Dr Joseph Cheriyan
Why use drugs?
To improve quality or quantity
of life

To cure, suppress or prevent
disease

Before starting treatment !
Decide:
1. Whether one should use a drug at all and, if so -
2. What one hopes to achieve.
3. That the drug chosen will bring this about.
4. What other effects the drug might have and
could these be harmful?
5. Does benefit outweigh risk?
Risk vs Benefit

Negligible risk
 Acceptable

risk
Unacceptable risk
How does one choose a drug?
Efficacy
Safety & tolerability
 Cost-effectiveness

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
History of adverse reactions?
“I can’t take antibiotics, they make me ill,
doctor”
Which specific drugs?
 When?
 Actual adverse reaction, beware “allergy”
 Similar drugs since?

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)
NB Copies of this Yellow Card are contained in your BNF
Responsibilities of the physician?
Not to be ignorant of existing knowledge
or important new developments
 To adopt new developments of proven
value (evidence-based prescribing)
 To prescribe accurately and clearly
 To avoid inappropriate prescribing
 To tell patients what they need to know
 To accept responsibility for one’s actions

What should we tell the patient?
 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 treatment
 Whether and how the patient will judge
benefit
 How soon benefit can be expected

What should we tell the patient?
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 alcohol and
other medicines

The prescription – pitfalls
Doses

Route
– Choose appropriate route e.g. vomiting?
– Care with doses e.g. Penicillin 1.2g iv
versus 1.2mg intrathecal
– Do not use the im route if patient is
anticoagulated
The prescription – pitfalls
Doses

Vancomycin
– Cl difficile 125mg qds PO
– Staph aureus 1g bd IV
The prescription – pitfalls
Doses

Dose reduction
– Elderly, renal failure, hepatic failure

Children
– Dose often calculated by weight
– Paediatric pharmacopoeia available
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
The prescription – pitfalls
Cost

Cl Difficile
– Metronidazole £1-50
– Vancomycin £105-00
Contra-indications
 Absolute
–  blockers and asthma
– Misoprostol and pregnancy

Relative
– Ciprofloxacin and epilepsy
Interactions

Two drugs together
 blockers and verapamil
– Phenytoin and the OCP
– Ciprofloxacin and theophylline
– Enzyme inducers vs. enzyme inhibitors
–

Nutrition
– NG feeding and phenytoin

Diseases
– Ampicillin and EBV
Special situations

Pregnancy
– Avoid all drugs if possible – ACEI, gentamicin,
carbimazole, isotretinoin, misoprostol

Breast feeding
– Avoid most drugs – ciprofloxacin, amiodarone

Renal / Hepatic impairment
– Avoidance, or change in dose – gentamicin,
opiates
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. statins for IHD and ACEI for
heart failure)
Compliance
 Also:
adherence / concordance / co-operation
25-50% of patients take < 90% of prescribed
dose

May be due to poor understanding, so cannot
comply


Can occur in the face of good understanding
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

How can we improve compliance?
Form a ‘partnership’ with the patient
 Provide oral and written information
 Rationalise drug therapy
 Plan treatment around the patient’s life
 Use ‘patient-friendly’ packaging
 Use combined fixed-dose & SR formulations
 See the patient regularly
 Use dosette box if appropriate

Summary
Prescribing is an important
responsibility
 Potential to do harm as well as good
 Good prescribing is fundamental to
being a good doctor

“Poisons in small doses are the best
medicines; and useful medicines in
too large doses are poisonous”
William Withering 1789
Drug Calculations and Prescriptions
Question 1
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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.
Answer

a) Check not on oral Theophylline. If so not for loading
dose and check plasma theophylline levels.

b) Loading 300mg bolus over at least 20 minutes.
Written on yellow infusion chart as:
Date: 7/11/3 Line: IV Type of fluid/blood: 5%dextrose or 0.9%
Saline
Additives: Aminophylline 300mg
Volume:
100 ml Rate: over 20 mins. SIGN!!
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Maintenance = 30mg/hour. Written on yellow
infusion chart as:
Date: 7/1/3 Line: IV Type of fluid: 5% Dex or saline 0.9%
Additives: Aminophylline 500mg Volume: 500ml
Rate: 30ml/hour ; SIGN!!
or 500mg in 250 ml glu/saline at a rate of 15ml/hour.

Question 2
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.
 Write out a prescription for this on the
appropriate chart
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: 7/11/3 Drug: Lidocaine 2% Dose:200mg
Time: as and when given and SIGN!!
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Route: S/C
Question 3
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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.
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: 7/11/3 Line: IV
Type of fluid: Saline 0.9% Additives:
Phenytoin 1200mg Volume: 200ml Rate: 8ml/min SIGN!!
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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:
7/11/3 Circle frequencies eg 8,14,22 Additional
Instructions: in 100 ml saline SIGN!!!
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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.
Answer
N-Acetyl 7500mg in 200ml 5%glu 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
5% dextrose
5% dextrose
And SIGN!!
N-Acetlycysteine 7500mg
N-Acetylcysteine 2500mg
N-Acetylcysteine 5000mg
200ml
over 15 minutes
500ml
1 litre
over 4 hours
over 16 hours
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
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: 7/11/3
Additional instr: in 200 ml saline 0.9%
Freq: Circle 8,14,22
SIGN!!
