THERAPEUTIC DRUG MONITORING (PowerPoint) by liaoqinmei

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									Therapeutic Drug
Monitoring (TDM)
   Pharmacy Department
         QEPH
    INDICATIONS FOR TDM

• What therapeutic information can be
  derived from this test?




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  INDICATIONS FOR TDM
1.Treatment seems ineffective
• Patient compliant -TDM confirm dose too low
• Patient non-compliant -TDM will confirm if
  drug has been taken BUT NOT HOW MUCH.
2. Drug is Toxic (at normal doses)
• Useful if symptoms of intoxication are difficult
  to distinguish from that of the underlying
  condition (Digoxin in Heart Failure) - TDM to
  confirm level, then decide the course of
  action
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...INDICATIONS FOR TDM...
3. Eliminating impaired organ function
• kidney/liver function is impaired - reduced
  drug elimination
--TDM-reduce dose and by how much

4. Drug Interaction
• giving 2 drugs together is likely to result in a
  pharmacokinetic drug interaction
--TDM -helps to assess the importance of the
  interaction and whether to change the drug
  dosage.

                                                     4
    INDICATIONS FOR TDM
• When a patients condition is refractory to a
  particular dose regimen
• When adjusting a dose regimen or
  changing formulation
• To establish a base line value after a
  person exhibits a satisfactory response



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             Value of Results
Results valuable if you have
 information on:-
•   All the drugs the patient is receiving
•   The dose regime and dose form
•   Time of day of sample
•   Time of last dose
•   Is the level a peak or trough or in between
•   Clinical status of patient
                                                  6
            Drugs to TDM

•   Phenytoin
•   Phenobarbitone
•   Carbamazepine
•   Lamotrigine?
•   Valproate?


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Diagram showing drug at steady state




                        Steady state




                                       8
             Reminder
Half-life
• The time for the drug in the body to fall
  by half remains constant
Steady state
• rate of elimination = rate of dosing
• achieved after 5 half lives have passed
• sampling sooner is of no value unless a
  loading dose is given or you suspect drug
  toxicity
Sample time
• depends on the half life of the drug and
  the dosing interval                         9
              Target range Sample     Steady
                           Time       State

Phenytoin     7-20mg/l      Pre-dose 5 days
Phenobarb     10 - 35mg/l   anytime 10 days
Carbamazepin 4 - 12mg/l   Pre-dose    10 days
e            >7mg/l (bpd)
Lamotrigine   ? < 15mg/l    anytime   5 days
Valproate     40 -100mg/l   anytime 30 hours



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           Target ranges
• Use the ranges only as a guide
• Clients may:
  -respond well to levels < target range
  -experience side effects at levels
  within the range
  - need/tolerate levels >target range

• NEVER interpret the serum conc. of a
  drug in isolation - look at the clients
  clinical condition                      11
                Phenytoin
• Non-linear kinetics
• Relation between daily dose and serum
  conc. varies amongst individuals and
  successive equal dose increments raise
  the conc by an increasing amount
• Half life 22hours (7-42 hours)
• Due to its kinetics-use same preparation
• Remember 15mls (30mg/5mls) =100mg
  caps/tabs
• Monitor any change
                                             12
              Phenytoin
• If seizures are not controlled then adjust
  dose using the following regimen
  -conc<7mg/l then increase daily dose by
  100mg
  -conc is >7mg/l but <10mg/l then increase
  by 50mg daily
  -conc>10mg/l increase by 25mg daily
• Remember phenytoin is 90% bound to
  plasma proteins
• Binding is reduced-hypoalbuminaemia,
  CRF
  -the target range will be reduced            13
               Phenytoin
Protein binding influenced by
• hepatic and renal disease
• pregnancy
• drug interactions




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           Carbamazepine
• During 1st 2 wks -CBZ stimulates the
  activity of mono-oxygenase enzymes
  responsible for its own metabolism
• Whilst auto-induction occurs elimination
  half-life is continuously shortening and the
  serum concentration is not related to dose
• Max. induction occurs b/w 2-4 weeks
• Start at 100/200mg OD/BD increasing by
  100-200mg every 2 weeks.


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             Carbamazepine
• TDM -Initial stages of treatment
       -drug interaction suspected
       -toxicity suspected
• Active metabolite which is not routinely
  measured
• Wide variation in individual tolerance
• Timing of sample most important



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• Valproate-levels bear no relationship to
  the mode of action of the drug since the
  pharmacokinetics varies in individual
  -only monitor compliance/intoxication

• Lamotrigine-no correlation between level
  and symptom control/side effects
  -only monitor if adding to another AED
• Important interaction between valproate
  and lamotrigine

CSM- concurrent use of Valproate with
  Lamotrigine is one of the main risk factors
  for developing serious skin reactions to
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  Lamotrigine
Treat the patient not the blood
             level

								
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