CPT2: TDM

Question 1

What is therapeutic drug monitoring?

Answer 1

Individualisation of dosage by maintaining plasma drug concentrations within a target range

◦Therapeutic range (TR) or therapeutic window (TW)

(looking at variety if PK parameters and using these to provide the best care in patients)

Question 2

What are the 2 main causes of variatio in drug response between individual patients

Answer 2

• Pharmacokinetics - dose and [Drug] in plasma
• Pharmacodynamics - [Drug] at receptor and effect of drug

Question 3

What are PK sources of varibability?

Answer 3

• Age
  
  • Neonates, children, elderly
• Physiology
  
  • Gender, pregnancy
• Disease
  
  • Hepatic, renal, cardiovascular, respiratory
• Drug interactions
  
  • Environmental influences on drug metabolism. E.g. smoking
• Genetic polymorphisms of drug metabolising enzymes
• Physiochemical properties of drug itself

The wide range of variables in indivuals mean that drug treatment needs to be individual for each patient

Question 4

What drug characteristics need to be present for TDM to be helpful?

Answer 4

Drug characteristics which indicate the requirement for TDM are;

• Marked PK variability
  
  • Cyclosporin, digoxin, gentamicin, lithium, theophylline
  • ADME varies from person to person
• Therapeutic and adverse effects related to drug concentration (overlap)
  
  • Anticonvulsants, digoxin, theophylline
  • E.g. Anticonvulsants - seizures could either be caused by lack of therapeutic effect or by toxic amounts. A blood test can determine which is the case
• Narrow therapeutic index – potentially life threatening toxicity at concentrations even slightly above target range
  
  • Lithium, phenytoin, digoxin
• Non- linear PK
  
  • Phenytoin
  • Can saturate drug metabolising enzymes at therapeutic concs
• Specific targets for peak/trough concentrations
  
  • Gentamicin, vancomycin
  • Damaging to elimminating organs e.g. gentamicin is nephrotoxic as primary excreted by renal

Question 5

Question 6

Indications for TDM

Answer 6

• Patients with impaired clearance of narrow TI drugs
  
  • ​Must know clearance mechanism of drug
    
    • e.g. renal failure - clearance of digoxin increase, increased chance of toxicity
• Where symptoms of underlying disease are hard to distinguish from ADR
  
  • Digoxin and phenytoin: both have side effects that are similar to the conditions which they are used to treat (phenytoin – fits, digoxin - cardiac dysrhythmias).

Question 7

Situations when Drug monitoring may not be useful

Answer 7

• Drugs which can be given in very large doses without ADR
  
  • Penicillin
• Where better means of assessing drug effect are available
  
  • Monitoring warfarin by INR not serum levels
• In assessing patient compliance
  
  • Can’t distinguish poor compliance from rapid metabolism

Question 8

Describe monitoring of drugs in regards to clinical effect

Answer 8

• }Some clinical effects which can be readily measured and TDM easily applied
  
  • Heart rate, blood pressure
    
    • Adjust dose on basis of response
• Others can not
  
  • Drugs used prophylactically i.e. to maintain the absence of a condition
    
    • Seizures, cardiac arrhythmias, depressive or manic episodes, asthma relapse, organ rejection
  • To avoid serious toxicity
    
    • e.g. Aminoglycoside antibiotics which (unlike most antibiotics) have a narrow TW

Question 9

Answer 9

Question 10

Describe the steps of the TDM process of finding a treatment regime that is appropriate for the patient

Answer 10