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DRUG

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DRUG DRUG INTERACTIONS Dr.Abdul latif Mahesar King Saud University May 2010 * – PowerPoint PPT presentation

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Title: DRUG


1
DRUG DRUG INTERACTIONS
  • Dr.Abdul latif Mahesar
  • King Saud University
  • May 2010

2
DRUG DRUG INTERACTION
  • When one drug is administered, a response
    occurs, if a second drug is given and response to
    other drug is altered , a drug interactions is
    said to have occurred
  • This effect may be
  • Desired or beneficial (efficacy ?es with out ?in
    toxicity)
  • e.g. Multi drug treatment of T.B
  • Amoxicillin clavulanic acid
  • L-Dopa Carbidopa
  • Naloxone to treat Morphine overdose

3
  • Undesired or harmful (toxicity is ?ed with ?in
    efficacy)
  • Aspirin and Warfarin
  • Propranolol Salbutamol
  • Paracetamol Alcohol
  • Gentamycin loop diruetics

4
  • Clinically important drug interactions
  • 1. Drugs that have steep dose response curve and
    small therapeutic index, small change in
    concentration at site will lead to substantial
    increase in effect.
  • e.g. Digoxin , Lithium
  • 2. Drugs that are known enzyme inducers/inhibitors

5
  • 3. Drugs that exibit saturable metabolism
  • e.g. Phenytoin , Theophylline
  • 4. Drugs used for prolong period and precise
    plasma concentration are required
  • e.g. oral contraceptive , antiepileptic drugs
    , lithium
  • Different drugs used to treat same disease
  • e.g. Theophylline, Salbutamol
  • 6. In patients with impaired kidney and liver
    functions
  • 7. In elderly who receive several drugs at the
    same time

6
PHARMACODYNAMIC INTERACTIONS
  • Both drugs act at same target site exerting
    synergism or antagonism
  • Drugs may act at same or different receptors or
    process.
  • The effect may be Synergistic or Antagonism

7
SYNERGISTIC PHARMACODYNAMIC DRUG INTERACTIONS  
8
DRUG INTERACTIONS MAY BE ANTAGONISTIC
9
PHARMACOKINETIC INTERACTIONS
  • Drug act remotely from target site to alter
    plasma concentration
  • e.g. enzyme induction /inhibition
  • interaction may be synergistic or antagonistic.
  • Drug interaction can occur at
  • out side the body
  • At site of absorption
  • During drug distribution
  • During drug metabolism
  • During drug excretion.
  • On receptor or body system.

10
Interaction out side the body
  • Drugs are added to reservoir or syringes to make
    drugs soluble they are prepared in salt forms,
    mixing these drugs may lead to precipitation
    (incompatibility)
  • Dilution in reservoir may also lead to loss of
    stability.
  • Protamine in zinc insulin may bind with soluble
    insulin and delay its effects.

11
AT THE SITE OF ABSORPTION
  • Direct chemical interaction
  • e.g. Antacids Tetracycline's ,Iron form
    insoluble complexes ,this can be prevented if
    drugs are administered at 2hrs apart.
  • Gut motility drugs which reduce gastric
    emptying delay absorption of other drugs
  • e.g anti cholinergics , antidepressants
  • .

12
PHARMACOKINETIC INTERACITONS     AT THE
ABSORPTION LEVEL EXAMPLES
13
  • Purgatives reduce time spent in small intestine
    and reduce absorption.
  • Alteration in gut flora antimicrobials
    potentiates ant coagulants by reducing bacterial
    synthesis of vit.K
  • Affect the transport as P-glycoprotein
  • Other than gut Local anesthetics (xylocaine)
    and adrenaline.

14
DURING DISTRIBUTION
  • Displacement from plasma proteins binding
  • e.g. Sodium valproate displaces Phenytoin
  • Sulphonamides displaces bilirubin ( in
    neonates)
  • Displacement from tissue binding sites
  • e.g. Quinidine displaces Digoxin

15
Interaction during metabolism
  • Enzme induction
  • liver micsrosomal enzymes are induced by a wide
    variety of drugs and these affect the metabolism
    of other drugs reducing their concentration and
    hence effect.
  • e.g oral contraceptive metabolism is enhanced if
    Phenytoin is co-administered ,leading to
    unplanned pregnancy
  • eg loss of anticougulant effect of Warfarin
    leading to danger of thrombosis if barbiturates
    are administered.
  • chronic use of alcohal shows tolerance to
    general anesthetics.

16
EXAMPLES INCLUDE
17
Enzyme inhibition
  • Certain drugs inhibit the liver microsomal
    enzymes ,hence increase the activity of drugs
    which are to be metabolized by these enzymes.
  • Eg. Cimetidine potenciates the effects of
    propranolol ,theophylline, warfarin and others

18
INTERACTIONS OF LIVER ENZYME INHIBITORS
19
Enzyme inducers.
  • Phenobarbital
  • Rifampin
  • Grisofulvin
  • Phenytoin
  • Ethanol
  • Carbamazepine

20
Enzyme inhibitors
  • Phenylbutazone
  • Metronidazole
  • Cimetidine
  • Omperazole

21
DRUG EXCRETION
  • MAY BE CHANGED BY DRUGS WHICH ALTER
  • URINARY pH
  • ? WEAK ACIDS LIKE (PENICILLINS,
  • PHENOBARB, ACETAZOLAMIDE,
  • NITROFURANTOIN).
  • BEST ELIMINATED IN ALKALINE
    URINE
  • ? BASES LIKE (CHLOROQUINE,
    IMIPARMINE,
  • QUININE)
  • BEST ELIMENATED IN ACIDIC URINE B) OR
    DRUGS MAY COMPETE FOR RENAL TUBULAR SECRETION

22
DRUG EXCRETION  EXAMPLES  
23
Haemodynamic flow
  • variation in heaptic blood flow may influence the
    rate of inactivation of drugs as in reduced
    cardiac out put.
  • Drugs which reduce cardiac out put like
    Propranolol may reduce the metabolism of other
    drugs.

24
  • B- Drug may alter drug distribution Mechanisms
  • Competition for plasma protein binding
  • Displacement from tissue binding sites
  • Alterations in local tissue barriers (P-glyco
    proteins inhibition in BBB).

25
  • Displacement from tissue binding sites would tend
    to transiently increase blood concentration of
    !displaced drug.
  • This effect is transient because of
    compensatory increase in drug disposition.
  • When one displacing drug additionally reduces
    elimination of the 1st drug , so that free
    concentration is increased not only acutely but
    also chronically at new steady state, severe
    toxicity may occur.

26
Salicylates displace methotrexate from albumin
and also reduce its secretion into nephron by
competition with anion secretory carrier.
Quinidine, verapamil, amiodarone displace
digoxin from tissue binding sites reduce its
renal excretion leading to digoxin toxicity
27
  • Drugs metabolism
  • Drugs can either inhibit/ induce
    drug-metabolizing enzymes.
  • Enzyme inducers (stimulation of cytochrome P450
    in liver) requires some days
  • Barbiturates
  • Ethanol
  • Carbamazepine??
  • Phenytoin
  • Rifampicin??
  • Efavirenz??
  • They also increase glucuronidation (phase II)
    metabolism

28
  • Enzyme inhibitors (inhibit cytochrome P450)
    more quickly than enzyme induction
  • Amiodarone
  • Androgen??
  • Chloramphenicol
  • Cimetidine decrease warfarin metabolism
  • Ciprofloxacin, clarithromycin, erythromycin
  • Cyclosporine, ??isoniazide,?? ketoconazole,
  • Delavirdine??
  • Disulfiram.??
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