Clin Pktcs by thilak0505


									 Introductory Clinical

    Dr Alex Dodoo PhD, MPSGH, MRPharmS
Centre for Tropical Clinical Pharmacology &
          UGMS, Accra, GHANA
Email: OR
Why Clinical Pharmacokinetics?

   Manner in which drug is given is called DOSAGE
   Duration of drug therapy and dosage regimen
       To cure?
       To Mitigate?
       To prevent illnesses?
   All drugs have potential toxic effects which must be
    balanced against their benefits
   To achieve optimal therapy, the appropriate “drug of
    choice” must be selected based on:

Optimal Therapy
   For optimal the appropriate "drug of choice" must be selected
    based on
     Accurate diagnosis of the disease, knowledge of the clinical state
       of the patient and understanding of pharmaco-therapeutic
       management of the disease
   Then the following must be answered
     How often the drug is to be administered must be decided

     How much of the drug must be administered must be determined

     For how long must the drug therapy be maintained must be
   These factors are interlinked e.g. giving a bolus dose may lead to
    toxicity so need to balance convenience with toxicity
   The decisions taken MUST NOT be based on trial and error but
    on science and evidence

Drugs and the body

   Drugs are “foreign” to the body – xenobiotics
   Body has to “deal” them
   Two main actions
       Pharmacokinetic (what the body does to the drug)
       Pharmacodynamic (what the drug does to the body)
   Pharmacokinetics
       Absorption
       Distribution
       Metabolism
       Excretion


   Plasma concentration (Cp) of most drugs give good
    estimate of amount most likely to be at effector site
    (site of action – receptor site; within cells etc)
   Cp of anticonvulsants found to correlate well with
    concentration within brain tissue
   Cp of lithium, anticonvulsants reflects utility and
   Key idea behind therapeutic drug monitoring

Determinants of plasma drug
   The rate of INPUT into the plasma
   The rate of LOSS from the plasma
   The VOLUME in which the drug is distributed
   Each can be affected by several factors
   Input affected by rate of dissolution of formulation in
    gastric or duodenal juice, rate of gastric empting,
    rate of uptake through intestinal wall, rate of pass
    through the liver and into the systemic circulation,
    presence of efflux proteins etc

Key Concepts

   Half life – t1/2
       Time required for reduction to one-half initial drug activity or
        time taken by the body to eliminate half a given dose by
        metabolism and/or excretion
       Property of the drug
       Not dependent on the manner in which the drug is given
       Permits calculation of loading doses, total amount in the
        body etc
       Determines frequency of drug administration

Key Concepts
   Apparent volume of distribution
     Volume required to account for drug in the body

     Affected by binding to tissue and plasma proteins

     Not a real volume

   Clearance
     Determines rate at which drug leaves the body

   AUC
     Measure of drug exposure to the body

     Useful for determining bioavailability (relative, absolute) and
   Oral vs. Intravenous administration of drugs

   Patient factors affecting hepatic clearance
     Hormonal regulation (thyroid, pancreas, gonads)

     Gender

     Pregnancy (in general, Vd and CLR tend to increase while

      oxidative metabolic capacity tends to decrease)
     Race

     Food (malnutrition may decrease metabolism while high protein
      diet may increase metabolism)
      Food intake with or shortly after (< 3 hr) food may decrease first
      pass effect)
     Food appears to directly and transiently inhibit the enzymes

      associated with intrinsic metabolic clearance and/or alters plasma
      protein binding
     Circadian variation


   Half life
       T1/2 = 0.693/Kel
   Volume of distribution (Vd)
       Total amount of drug in the body DIVIDED by
        blood/plasma concentration at time zero
   Clearance
       Kel x Vd

Importance of clinical pharmacokinetics

   Calculation of loading doses
   “Topping up” low plasma concentration
   Working out rates of continuous intravenous
   Calculation of dosing intervals (od, bd, tds,
   Management of toxicity
   Drug Design – including production of
    modified release dosage forms

Tips for pharmacological treatment of patients
   Select the correct group of drugs
       Knowledge about the pathophysiology involved in the clinical
        situation of each patient and the pharmacodynamics of the
        chosen group of drugs, are fundamental principles for rational
   Selecting the correct drug from the chosen group
       The selection process must consider benefit/risk/cost information
        based on evidence about maximal clinical benefits of the drug for
        a given indication (efficacy) with the minimum production of
        adverse effects (safety)
   Verify the suitability of the chosen pharmaceutical
       The prescriber must check whether the active substance chosen,
        its dosage form, standard dosage schedule and standard
        duration of treatment are suitable for each patient
       Drug treatment should be individualized to the needs of each

Be aware of variations in dose response

   Variation in dose response may be due to:
       Drug formulation
       Body weight and age
       Physiological and pharmacokinetic variables
       Pharmacodynamic variables
       Disease variables e.g. liver disease, kidney disease
       Environmental variables
           High protein diets, charcoal cooked foods act as metabolizing
            enzyme inducers
           Drug oxidation rates are decreased in infantile malnutrition
            and in malnourished elderly populations


   Clinical pharmacokinetics important in
   Bedrock of drug design and setting of
    therapeutic regimen
   Important in individualisation of therapy


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