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    Drug Interactions: Dr. Jatin Dhanani

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    Riddhi Jain
    Drug interactions can occur when two or more drugs are taken together. They can be pharmacokinetic, affecting absorption, distribution, metabolism or excretion of the drugs. Or pharmacodynamic, affecting the drugs' effects at receptor or tissue levels. Drug interactions can be beneficial, like levodopa and carbidopa working synergistically in the brain. But they can also cause adverse effects like increased bleeding risk when nonsteroidal anti-inflammatories are taken with anticoagulants. Many factors increase risk of interactions, like taking multiple drugs, drugs with narrow therapeutic indices, or drugs that induce or inhibit drug-metabolizing enzymes. Foods and herbal supplements can also interact with prescription medications.

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    Drug Interactions: Dr. Jatin Dhanani

    Uploaded by

    Riddhi Jain
    27 views22 pages
    Drug interactions can occur when two or more drugs are taken together. They can be pharmacokinetic, affecting absorption, distribution, metabolism or excretion of the drugs. Or pharmacodynamic, affecting the drugs' effects at receptor or tissue levels. Drug interactions can be beneficial, like levodopa and carbidopa working synergistically in the brain. But they can also cause adverse effects like increased bleeding risk when nonsteroidal anti-inflammatories are taken with anticoagulants. Many factors increase risk of interactions, like taking multiple drugs, drugs with narrow therapeutic indices, or drugs that induce or inhibit drug-metabolizing enzymes. Foods and herbal supplements can also interact with prescription medications.

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    drugs

    Original Title

    4. Drug Interactions

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    Drug interactions can occur when two or more drugs are taken together. They can be pharmacokinetic, affecting absorption, distribution, metabolism or excretion of the drugs. Or pharmacodynamic, affecting the drugs' effects at receptor or tissue levels. Drug interactions can be beneficial, like levodopa and carbidopa working synergistically in the brain. But they can also cause adverse effects like increased bleeding risk when nonsteroidal anti-inflammatories are taken with anticoagulants. Many factors increase risk of interactions, like taking multiple drugs, drugs with narrow therapeutic indices, or drugs that induce or inhibit drug-metabolizing enzymes. Foods and herbal supplements can also interact with prescription medications.

    Copyright:

    © All Rights Reserved
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    27 views22 pages

    Drug Interactions: Dr. Jatin Dhanani

    Uploaded by

    Riddhi Jain
    Drug interactions can occur when two or more drugs are taken together. They can be pharmacokinetic, affecting absorption, distribution, metabolism or excretion of the drugs. Or pharmacodynamic, affecting the drugs' effects at receptor or tissue levels. Drug interactions can be beneficial, like levodopa and carbidopa working synergistically in the brain. But they can also cause adverse effects like increased bleeding risk when nonsteroidal anti-inflammatories are taken with anticoagulants. Many factors increase risk of interactions, like taking multiple drugs, drugs with narrow therapeutic indices, or drugs that induce or inhibit drug-metabolizing enzymes. Foods and herbal supplements can also interact with prescription medications.

    Copyright:

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    of 22

    Drug

    Interactions
    Dr. Jatin Dhanani

    modification of response to one drug by another


    when they are administered simultaneously
    or in quick succession

    Quantitative

    Qualitative

    Outcomes of drug interactions


    1)Loss of therapeutic effect
    2)Increase/decrease in pharmacological activity
    3)Toxicity
    4)Beneficial effects

    Drug interaction
    results in
    Beneficial effects

    Combinations

    Adverse effects

    Treatment of Poisoning

    Ethyl alcohol in methyl alcohol poisoning


    Co trimoxazole
    Desferioxamine in iron poisoning
    Levodopa + carbidopa
    Protamine sulfate in heparin poisoning
    Penicillin + probenecid
    Other
    Thiazide diuretics
    chelating agents in mineral poisoning
    + triameterine
    Physostigmine
    Amoxicillin + clavulinic
    in atropine poisoning
    acid

    Adverse
    Drug Interactions

    Factors increases chances

    Self medication
    Treatment with semi qualified paramedical staff or
    quacks
    Undue/ indiscriminate prescribing
    Drug with steep DRC or low therapeutic index
    Known enzyme inducer or inhibitor
    Follows zero or saturation kinetics
    Drug which use for prolonged period of time with precise
    maintenance of plasma conc.
    Severely ill patients, who receive many drugs at a time
    Elderly having multiple pathology & so, receiving many
    drugs at a time

    Pharmacological basis for


    drug interactions
    In vitro

    In vivo

    Thiopental sod. + succinyl choline precipitate/


    inactivation
    Hydrocortisone + heparin or penicillin inactivation
    of heparin or penicillin
    Sod. salt of Phenytoine, barbiturates, sulfonamides.
    Heparin, penicillin never added in Dextrose sol.
    precipitated

    In vivo drug interactions


    Pharmacokinetic

    Pharmacodynamic

    Altered GIT Absorption

    Altered pH,
    Altered bacterial flora,
    formation of drug chelates or complexes,
    Drug induced mucosal damage
    altered GIT motility

    Altered pH

    Ex1.,

    antiacids Increase the pH

    Ex2.,

    Decrease the tablet


    dissolution
    of Ketoconazole (acidic)

    H2 antagonists pH

    Therefore, these drugs must be separated by at least 2h


    in the time of administration of both

    Altered intestinal bacterial flora

    EX., In 10% 0f patients receive digoxin..40% or more of the


    administered dose is metabolized by the intestinal flora

    Antibiotics kill a large number of the normal


    flora of the intestine
    Increase digoxin conc.
    and increase its toxicity

    Complexation or chelation
    Ex - 1 Tetracycline interacts with iron preparations

    or
    Milk (Ca2+ )

    Unabsorbable complex

    Ex - 2 Antacid (aluminium or magnesium) hydroxide


    Decrease absorption of
    ciprofloxacin by 85%
    due to chelation

    Drug-induced mucosal damage


    Antineoplastic agents e.g., cyclophosphamide
    vincristine
    procarbazine
    Inhibit absorption
    of several drugs
    eg., digoxin

    Altered motility
    Metoclopramide (antiemetic)

    Increase the toxicity


    of cyclosporine

    Increase absorption of cyclosporine due


    to the increase of stomach empting time

    Altered distribution
    Displacement from plasma protein binding
    Depends on the affinity of the drug to plasma protein
    Phenytoin (90%), Tolbutamide (96%), and warfarin (99%)
    highly bound to plasma protein

    Drugs that displace these agents are Aspirin


    Sulfonamides
    phenylbutazone

    Displacement from tissue binding


    Digoxin highly tissue binding
    quinidine displace the digoxin and increase its toxicity

    Altered metabolism
    Enzyme inhibition

    Enzyme induction

    Adverse
    consequences

    Increase bleeding
    tendency with dicumerol
    when given with
    cimetidine
    Severe respi depression
    with morphine when
    given with MAOIs

    Therapeutically
    beneficial reactions

    Increase accessibility of
    L-DOPA in brain when
    given with carbidopa
    Disulfiram as deaddiction
    Reversal of skeletal
    muscle paralysis due to
    d-tubocurarine by
    neostigmine

    consequences
    Contraceptive
    failure
    Enzyme
    induction
    (refampicin and phenytoin
    inhibit action of OC pills)
    Warfarin require higher
    dose if given along with
    enz inducer barbiturates
    Barbiturates induce its
    own metabolism if given
    for longer time (tolerance
    development)
    Paracetamol toxicity in
    chronic alcoholic patient

    Therapeutic
    utilization of enz
    induction

    To treat neonatal
    jaundice:
    phenobarbitone induce
    fetal hepatic glucuronyl
    transferase, which
    metabolize bilirubin

    N.B enzyme induction involves protein synthesis .Therefore,


    it needs time up to 3 weeks to reach a maximal effect

    Altered excretion

    Altered Glomerular filtration

    Altered reabsorption

    Methylxanthines increase renal blood flow


    Alkalization of urine by sod. bicarbonate increase
    excretion of acidic drugs like aspirin, barbiturates
    Acidification of urine by ascorbic acid or ammonium
    chloride increase excretion of basic drugs like
    amphetamine & morphine

    Altered tubular secretion

    Probenecid blocks active tubular secretion of


    penicillin, cephalosporin, zidovudine and so prolongs
    the action
    Quinidine decrease tubular secretion of digoxin

    Pharmacodynamic drug
    interactions
    At
    receptor level
    At tissue or systemic level
    Synergism
    Additive

    Supraadditive

    Antagonism

    At systemic/ tissue level

    Loss of antihypertensive effect of ACE


    inhibitors & ARBs by NSAIDs such as
    indomethacin, ibuprofen, piroxicam (possibly due
    to inhibition of vasodilator PG formation by
    kidneys leading to Na retention)
    Severe hypotension with GTN when given with
    sildenafil
    Bradycardia with CCB (sp. verapamil) and blockers
    Hypokalemia with loop diuretics + thiazide
    Lithium toxicity with diuretics (Li absorption
    increase at PCT)

    Drug interaction
    Extended to
    Drug food interactions
    Drug herbal interactions
    Drug laboratory test interactions
    Drug disease interactions

    Drug food interactions

    Presence of food (sp. fatty food) absorption


    of most drugs
    Milk decreases absorption of iron and
    tetracycline
    Grapefruit juice - absorption of cyclosporine
    but inhibit metabolism of phenytoin,
    tetracycline and amioderone
    Cheese reaction

    Drug herb interacitons

    Aloe-vera latex have laxative properties and


    also blood sugar level laxatives and antidiabetic drug require caution
    Garlic,Ginger & Ginkgo biloba increase
    bleeding tendency with antiplatelet and
    anticoagulant drugs
    Garlic decrease gastrokinetic effect of
    metoclopramide, domperidone and cisapride
    St. Johns wort leads to photo toxicity if use
    with tetracycline, sulfonamide or PPI & increase
    CNS depression of CNS depressant drugs

    Drug laboratory test


    interactions

    Cephalosporin false +ve urine sugar test


    Diuretics interfere with electrolyte (Na+,K+)
    result
    Estrogen in contraceptive pills increase
    thyroxin value b/c of in thyroglobulin level
    Alcohol - -glutamyl transferase level

    Thank You

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