THERAPEUTIC DRUG MONITORING

Metformin [Ref. K.D.T. 6^th/e p 35]

Therapeutic drug monitoring is particularly useful in the following situation

(i) As a guide to the effectiveness of the therapy

• Plasma gentamycin and other antimicrobials against sensitive bacteria.
• Plasma theophylline for asthma.
• Blood cyclosporine to avoid transplant rejection.

(ii) When the desired effect is suppression of infrequent sporodic events such as:

• Epileptic seizures (anticonvulsants)
• Episodes of cardiac arrythmia (antiarryhthmics)

(iii) To reduce the risk of adverse drug effect (therapeutic index low)

• Digoxin
• Anticonvulsants
• Antiarrythmics
• Theophylline
• TCA
• Aminoglycoside
• Lithium

(iv) When lack of therapeutic effect and toxicity may be difficult to distinguish

• Digoxin is both a treatment for and sometime the cause for supraventricular tachycardia, therefore a plasma
  digoxin measurement will help to distinguish whether an arryhthmia is due to too little or too much digoxin.

(v) When there is no quick and reliable assessment of effect

• Lithium for mood disorder.

(vi) To check patient compliance on a drug regimen, when there is a failure of threrpaeutic effect at a dose that is expected to be effective.

• Antiepilepsy drug

(vii) Poisoning and overdose

Monitoring of plasma concentration is of no value for

(i) Cases where dose can be titrated against a quickly and easily measured effect such as

• Antihypertensive             -9            Blood pressure (B.P. can be easily monitored)
• Diuretics                        —>        Body weight
• Hypoglycemics               –4           Blood sugar (blood glucose level can be easily monitored)
• Oral anticoagutants         —>       INR

(ii) Plasma concentration has no correlation with effect

• This is the case with drugs that act irreversibly and these have been named hit and rundrugs” because their effect persits long after the drug has left the plasma
• Such drugs destroy or inactivate target tissue (enzyme, receptor and restoration of effect occurs only after days or weeks).

A drugs therapeutic window is the minimum dosage necessary for a patient to benefit from the main effects intended of a specific drug.

While main effects become present and are maximized, side effects are minimized.

This allows the patient to benefit from the therapeutic effect of the drug without suffering side effects that are more likely to be present if the optimum dosage is exceeded.

Ans. is ‘a’ i.e., Carbamazepine

Therapeutic window

The term therapeutic window refers to the range of doses of a drug that are actually effective in treating a particular disease.

• It is the range of dosage that can effectively treat a condition while still remaining safe, i.e. therapeutic window is the range between the lowest dose that has a positive effect and the highest dose before the negative effects outweigh the positive effect.
• Doses below the therapeutic window are too weak to have any effect and doses above the window cause unacceptable side effects.

o In a literal sense, therapeutic window is same as therapeutic range.

o So, every drug will have a therapeutic window, i.e. the range of dose or plasma concentration below which the drug is ineffective and above which the drug causes unacceptable side effects.

• But, in general the drugs which have narrow therapeutic window (narrow therapeutic range) are considered to show therapeutic window phenomenon.

o These drugs have already been listed in previous explanations. Drugs are

i)      Antiepileptics —> Phenytoin, carhamazepine, Lignocaine                       v) Lithium

ii)     Tricyclin antidepressants — imipraminc                                           vi) Aminoglycosides

iii)    Theophylline                                                                               vii) Digoxin

iv)    Cyclosporine

Note : According to KDT answer is ‘d’ i.e., clonidine: Read below

Therapeutic window phenomenon

 Optimal therapeutic effect is exerted only over a narrow range of plasma drug concentration or drug doses; both above and below this range, beneficial effects are suboptimal ie. the effect declines if the doses arc increased beyond a certain level.

• Examples are : Tricyclic antidepressants (imipramine), Clonidine, Glipizide

o But, I am in favour of Goodman & Gilman, because I have done extensive search on that, all other standard text books and various articles have mentioned the same as Goodman & Gilman.

o You are free to choose your favourite.

Ans. D: Gentamycin

Ans. is ‘d’ i.e., Digoxin

Therapeutic drug monitoring is particularly useful in following situations ‑

1. Drugs with low safety margin ‑

1. Digoxin
2. Aminoglycoside antibiotics
3. Anticonvulsants
4. Lithium
5. Antiarrythmics
6. Tricyclic antidepressants
7. Theophylline

2. If individual variations are large → Antidepressants, Lithium

3. Potentially toxic drugs used in presence of renal failure → Aminoglycoside antibiotic, vancomycin, cyclosporine

4. In case of poisoning

5. In case of failure of response without any apparent reason → Antimicrobials

6. To check patient compliance -. Psycho-pharmacological agents.

Drugs whose response is easily measurable eg. hypoglycaemics (metformin), antihypertensive, diuretics, oral anticoagulants and general anaesthetics, monitoring of plasma conc. is of no value.

Ans. is d i.e., To check the therapeutic effects of drug

Therapeutic drug monitoring is Particularly useful in following situations:

l. Drugs with low safety margin –

• Tricyclic antidePressants
• Digoxin
• Anticonvulsants
• Antiarrythmics
• Theophylline
• Aminoglycoside antibiotics
• Lithium