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PPT ON PHARMACOKINETIC DRUG interaction BY SROTA DAWN
1. A brief review on
“PHARMACOKINETIC DRUG INTERACTION”
By
Srota Dawn.
M.Pharm(Pharmacology)
VELS UNIVERSITY
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2. INTRODUCTION
DRUG INTERACTIONs are said to occur
when the pharmacological activity of a drug is altered by
the concomitant use of another drug or by the presence
of some other substances.
A drug whose activity is affected by such interaction is
called as the object drug and the agent which
precipitates such an interaction is referred to as the
precipitants.
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3. Drug interaction includes –
1. Drug –drug interaction.
2. Food – drug interactions , for example, inhibition of several
drugs by grapefruit juice.
3. Chemical – drug interactions , for example, interaction of
drug with alcohol ,tobacco etc.
4. Drug – laboratory drug interactions , for example,
alteration of diagnostic test results by the presence of drug.
5. Drug – disease interactions , for example, worsening of
disease condition by the drug
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5. Factors contributing drug interactions
Some of the risk factors that lead to drug interactions include-
1. Multiple drug therapy :
e.g. therapy in patient suffering from hypertension
and congestive heart failure includes antihypertensive as well as
digitalis which together leads to abnormal heart rhythms.
2.Multiple prescribers :
some individuals go to more than one physician. e.g. one
doctor may prescribe an anxiolytic for a patient while another doctor
prescribes an antihistaminic drug having sedative properties with the
possible consequences of an excessive depressant effect.
3.Multiple pharmacological effect of drug:
most drug used in current therapy exhibit more than
one type of pharmacological action and have capacity to influence many
physiological system
e.g. antihistamines (secondary effect is sedation) enhance the
sedative effect of tranquillizers. 9/18/2013 3:28:28 AM 5
6. 4. Poor patient compliances :
This results when patient does not take medication
in the manner intended by the doctor; which may be due inadequate
instructions from the doctor pharmacist
5. Advancing age of patients :
Increased tendency of drug instructions episodes in
elderly is generally due to decreased in liver function in such
individuals.
6. Drug – related factors:
Clinically significant interactions are most likely to
occur between drugs that have potent effects , a narrow therapeutic
index and a steep dose response curve (e.g., cytotoxic , anti-
hypertensive , and hypoglycemic drugs, digitoxin , warfarin , etc.)
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7. Mechanisms of drug interactions
The mechanisms by which an interaction can
develop are –
The administration of one drug (A) can alter the action of
another (B) by one of two general mechanisms:
1. Modification of pharmacological effect of B
without altering its concentration in the tissue fluid
(pharmacodyanamic interaction)
2. Alteration of the concentration of B that reaches
its site of action (pharmacokinetic interaction) .
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8. Absorption
Distribution
Metabolism
Excretion
Piscitelli SC, Gallicano KD. N Engl J Med 2001;344:984-969/18/2013 3:28:28 AM
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9. 1. ALTERATIONS IN ABSORPTION
I. Complexation / Chelation
Example: antacids + tetracycline
Impact: tetracycline complexes with divalent
cations forming an insoluble complex
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10. 1. ALTERATIONS IN ABSORPTION
I. Complexation/Chelation
II. Altered GI Transit
Example: anticholinergics + acetaminophen
Impact: delay in absorption of acetaminophen
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11. 1. ALTERATIONS IN ABSORPTION
I. Complexation/Chelation
II. Altered GI Transit
III. Altered Gastric pH
Example: H-2 blockers + ketoconazole
Impact: dissolution of ketoconazole is
decreased, resulting in reduced absorption
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12. 1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
I. Induction of Metabolism
Example: phenobarbital + warfarin
Impact: phenobarbital increases the
metabolism of warfarin, resulting in reduced
anticoagulation
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13. D. CLASSIFICATION OF MECHANISM
1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
3. METABOLISM INTERACTION
I. Induction of enzyme: increased rate
of metabolism
I. Inhibition of enzyme: decreased rate
of metabolism
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14. 1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
3. METABOLISM INTERACTION
4. ALTERATIONS IN RENAL CLEARANCE
I. Increase in Renal Blood Flow
Example: hydralazine + digoxin
Impact: hydralazine increases the renal
clearance of digoxin
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15. 1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
3. METABOLISM INTERACTION
4. ALTERATIONS IN RENAL CLEARANCE
I. Increase in Renal Blood Flow
II. Inhibition of Active Tubular Secretion
Example: probenecid + penicillin
Impact: probenecid prolongs the half-life of
penicillin, allowing single dose therapy
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16. 1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
3. METABOLISM INTERACTION
4. ALTERATIONS IN RENAL CLEARANCE
I. Increase in Renal Blood Flow
II. Inhibition of Active Tubular Secretion
III. Alterations in Tubular Reabsorption
Example: antacids + aspirin
Impact: antacids reduce the tubular
reabsorption of salicylate via an increase in
urine pH 9/18/2013 3:28:28 AM 16
17. 1. ALTERATIONS IN ABSORPTION
2. ALTERATIONS IN HEPATIC METABOLISM
3. METABOLISM INTERACTION
4. ALTERATIONS IN RENAL CLEARANCE
5. ALTERATIONS IN PLASMA PROTEIN
BINDING
Example: phenytoin + valproic acid
Impact: protein binding of valproic acid is reduced
and total Css decreased
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19. EX1., Enzyme induction
A drug may induce the enzyme that is responsible
for the metabolism of another drug or even itself e.g.,
Carbamazepine (antiepileptic drug ) increases its own
metabolism
Phenytoin increases hepatic metabolism of theophylline
Leading to decrease its level
Reduces its action
and
Vice versa
N.B enzyme induction involves protein synthesis .Therefore,
it needs time up to 3 weeks to reach a maximal effect
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20. EX2., Enzyme inhibition;
It is the decrease of the rate of metabolism of a drug by
another one . This will lead to the increase of the concentration of the
target drug and leading to the increase of its toxicity .
Inhibition of the enzyme may be due to the competition
on its binding sites , so the onset of action is short
may be within 24h.
N.B; When an enzyme inducer (e.g.carbamazepine) is administered
with an inhibitor (verapamil) The effect of the
inhibitor will be
predominant
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21. Ex.,Erythromycin inhibit metabolism of astemazole and terfenadine
Increase the serum conc.
of the antihistaminic leading to
increasing the life threatening
cardiotoxicity
EX., Omeprazole
Inhibits oxidative
metabolism
of diazepam
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22. Pharmacodynamic interactions;
It means alteration of the dug action without change in its
serum concentration by pharmacokinetic factors.
EX., Propranolol + verapamil
Synergistic or additive
effect
1. Synergism means =1+1=3
2. Additive means= 1+1=2
3. Potentiation means= 1+0=2
4. Antagonism means 1+1=0 or 0.5
Effect at the receptor site
•Antiadrenegic
•anticholinergic
On the other hand
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23. Pharmacodynamic interactions:
In this case the activity of the object drug
at its site of action is altered by the precipitant . It
may be direct or indirect-
1.Direct pharmacodynamic interaction:
A. ANTAGONISM :
The interacting drugs drugs have opposing
actions,
e.g. Ach and NA have opposing action on
heart rate
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24. B. ADDITION or SUMMATION:
The interacting drugs have similar actions and
the resultant effect is the sum of individual
drug responses,
e.g. CNS DEPRESSANTS like sedatives
,hyponotics,etc.
C. SYNERGISM or POTENTIATION :
It is enhancement of action of one drug by
another,
e.g. alcohol enhances the analgesic activity of
aspirin.
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25. * Prevention of drug interaction
1) Monitoring therapy and making adjustments
2) Monitoring blood level of some drugs with narrow
therapeutic index e.g., digoxin, anticancer agents…etc
3) Monitoring some parameters that may help to
characterize the early events of interaction
or toxicity e.g., with warfarin administration, it
is recommended to monitor the prothrombin time
to detect any change in the drug activity.
4) Increase the interest of case report studies to
report different possibilities of drug interaction
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