B. TDM EXEMPLARS

Question 1

example of bronchodilators monitored

Answer 1

Theophylline
- Drug toxic effects difficult to distinguish from clinical symptoms
- Liver metabolism decreases due to heart failure, cirrhosis, viral infection and age (so increases drug conc) and increases in smokers, chronic alcoholics and other drug-drug interactions
- narrow therapeutic window

Question 2

example of antibiotics monitored

Answer 2

Gentamicin, Amikacin
- Narrow therapeutic window and nephrotoxicity at high concentrations

Question 3

examples of anti-cancer drugs monitored

Answer 3

Methotrexate
- High dosage methotrexate requires different levels of leucovrin rescue depending upon variation in excretion

Question 4

examples of immunosupressants monitored

Answer 4

Cyclosporine (to prevent rejection in organ transplants)
- Narrow therapeutic window and can cause nephrotoxicity
- Large variability in pharmacokinetics in single patient and patient-to-patient

Question 5

examples of psychoactive drugs monitored

Answer 5

Lithium, tricyclic antidepressants
- Narrow therapeutic window and many drug-drug interactions
- Lithium has inter and intra variability in PKs

Question 6

examples of cardiac drugs monitored

Answer 6

Digoxin, Procainamide, Lidocain

Question 7

examples of antiepileptics monitored

Answer 7

Phenobarbitone, Phenytoin, Carbamazepine

Question 8

when are TDM measurements only of value

Answer 8

if the plasma level reflects the therapeutic effect of the drug ie: a higher plasma level results in an increased therapeutic effect

Question 9

what is an important consideration in the use of TDM for digoxin and phenytoin

Answer 9

impaired renal function

Question 10

what may phenytoin (anti epileptic) toxicity cause

Answer 10

fits

Question 11

what may digoxin (heart drug) toxicity cause

Answer 11

cardiac dysrhythmias

Question 12

scenarios where monitoring phenytoin levels may be clinically useful

Answer 12

• establishing an individual therapeutic concentration
• aiding in diagnosis of clinical toxicity
• assessing patient compliance
• guiding dosage adjustments in patients likely to have greater pharmacokinetic variability
• TDM of phenytoin is often considered essential

Question 13

why is TDM of phenytoin needed

Answer 13

• narrow therapeutic range: 10–20 mg/L (µg/mL)
• dose dependent adverse effects: nystagmus (involuntary eye movement), vertigo, diplopia (double vision), ataxia, drowsiness, and speech disturbances
• highly protein bound (approximately 90% to serum albumin so only 10% active) and free phenytoin is what is producing the pharmacological effect
• unbound phenytoin increases in renal failure

Question 14

important factors for phenytoin TDM

Answer 14

• phenytoin metabolism is non-linear, zero order pharmacokinetics
• Css reached 2-4 weeks after initiating dose so won’t know for 2-4 weeks
• dose increments must not be >25-50 mg/day
• phenytoin sodium formulations are not bioequivalent to those containing phenytoin base, i.e. 100 mg of phenytoin sodium is approximately equivalent in therapeutic effect to 92 mg phenytoin base
• CEDIA (cloned enzyme donor immunoassay) method commonly used to measure phenytoin concentrations
• need to consider bound and unbound forms

Question 15

target sample conc and toxic range of digoxin

Answer 15

• 0.5-2microgram/l which is very narrow (depends what it’s being used for)
• > 2.4 µg/L

Question 16

when should you sample digoxin levels

Answer 16

in the trough

Question 17

when should you measure serum digoxin levels

Answer 17

at least 4 hours after an IV dose or 6 hours after oral dose

Question 18

why is there a risk of sampling at wrong time or too frequently with digoxin

Answer 18

• Half-life: 33-51 hours
• Steady state Css: 7- 10 days (possibly longer)

*if an adjustment is made you will need to wait another 7 days before you can check whether the desired steady state concentration has been reached

Question 19

why is TDM very important for digoxin

Answer 19

combination of narrow therapeutic range, low concentration for toxicity and long half life

Question 20

methods used to to monitor serum digoxin concentrations

Answer 20

• radioimmunoassay
• fluorescence polarisation immunoassay
• enzyme immunoassay

Question 21

criteria for TDM of digoxin

Answer 21

• borderline renal function
• possible drug accumulation
• hypokalemia or hypomagnesesmia can increase digoxin induced arrythmia
• aged subjects
• renal elimination reduces with age
• patients with rapid atrial fibrillation who require higher doses for heart rate control
• target concentration close to toxic level
• heart failure patients
  *require a lower dose (0.5-1 ug/L): exert a beneficial effect via neuro-hormonal modulation
• susceptible to inotropic stimulation by digoxin at higher concentration

Question 22

which drugs don’t need TDM

Answer 22

• most drugs don’t
• it’s expensive
• drugs used for treating diseases with clear clinical end points e.g., BP, HR, cardiac rhythm, blood sugar, blood cholesterol and triglycerides, urine volume, body temperature, inflammation, pain, headache (use obs instead)
• drugs whose serum concentrations do not correlate with therapeutic or toxic effects
• drugs with straightforward pharmacokinetics
• drugs used to treat diseases that are not life threatening

Question 23

role of pharmacist in TDM

Answer 23

hospital pharmacists may:
- advise other health care professionals about correct use of TDM-sampling time, sampling technique and interpretation of results
- select initial drug dosage regimen-dose, dosing interval, route of administration, dosage form
- revise and re-calculate dosage regimen depending upon TDM results and patient’s response
- assess various reasons for unexpected results (ie progression) such as non-compliance,
medication or laboratory errors
- evaluate and adjust dosage for patients on renal or haemodialysis
- advise and manage acute drug interactions

Question 24

how does TDM help to achieve optimal drug therapy

Answer 24

• maximises the desired pharmacological effect of the drug
• reaches this maximal effect in the shortest possible time
• decreases the risks of adverse effects and toxicity

Question 25

what type of kinetics does digoxin have

Answer 25

linear

Question 26

what type of kinetics does phenytoin have

Answer 26

non-linear