Pharmacovigilance, Drug Interactions

1. Adverse Drug reactions &
Pharmacovigilance
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AGRA PUBLIC PHARMACY COLLEGE, ARTONI, AGRA, UP, INDIA

2. Introduction-
➢ Drug or medical substances are always carries a certain risk of unwanted or
adverse effects. So, in health care need pharmacovigilance of such drug
action.
➢ Definition- “Pharmacovigilance is the science and activities relating to the
detection, assessment, understanding and prevention of adverse effects or
any other drug related problem”.
PHARMACOVIGILANCE
DRUG + KEEP WATCH
World Attention:- THALIDOMIDE DISASTER
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

3. DRUGS THAT HAVE BEEN WITHDRAWN OR HAVE HAD THEIR USES
RESTRICTED BECAUSE OF ADR
➢Pharmacovigilance system contribute to better knowledge and better
medical treatment of future patients.
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4. ADVERSE DRUG REACTIONS (ADR)-
➢ The WHO defines ADR as “A response to a drug which is noxious and
unintended, and which occurs at doses normally used in man for the
prophylaxis, diagnosis, or therapy of disease, or for the modifications of
physiological function”.
&
Adverse drug event (ADE)- “any untoward medical occurrence in a patient or
clinical investigation subject administered a pharmaceutical product and
which does not necessarily have a causal relationship with this treatment”.
➢ADE is a broader term, Thus all ADR are
adverse events but all adverse events are
not ADR.
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

5. Classification of ADRs-
Onset Of Event:
• Acute (<60 Minutes);
•Sub-acute (1-24 Hrs);
•Latent (>2 Days)
Frequency:
•Very common;
•Common;
•Uncommon;
•Rare/very rare
Severity:
•Mild;
• Moderate;
• severe
Mechanism:
•Intolerance;
•Idiosyncrasy;
• Drug Allergy;
• Drug interaction
Others:
•Side Effects;
•Secondary Effects;
•toxic effects;
•Photosensitivity;
•Drug Dependence;
•Teratogenicity;
•Carcinogenicity,
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

6. Pharmacological Classification-
Type A
(Augmented) Type B
(Bizarre)
Type C
(Continuous
Drug Use)
Type D
(Delayed)
Type E
(End Of Dose)
Type F
(Familial)
Type G
(Genotoxicity)
Type H
(Hypersensitivity)
Type U
(Unclassified)
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

7. ➢ Type A (Augmented/DOSE-RELATEDADVERSE DRUG REACTIONS)
reactions: Reactions which can be predicted from the known pharmacology of
the drug. Ex- insulin-induced hypoglycemia.
➢ Type B (Bizzare/NON-DOSE RELATEDADVERSE DRUG REACTIONS):
Cannot be predicted from the pharmacology of the drug. Type B reactions are
hypersensitivity reactions. Ex- Penicillin –Anaphylaxis.
➢ Type C (Continuous’/LONG-TERMADVERSE DRUG REACTIONS):
May be irreversible, unexpected or unpredictable. Type of reactions are
diseases that occur at a higher frequency among exposed patients than those
unexposed. Ex-Dementia by Anticholinergics.
➢ Type D (Delayed/ DELAYEDADVERSE DRUG REACTIONS): Occur
after many years of treatment. Ex-Analgesics – Nephropathy.
➢ Type E (End of treatment effect): Occur on withdrawal especially when drug
is stopped abruptly. Ex-Phenytoin withdrawal – Seizures.
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ARTONI, AGRA, UP, INDIA

8. Drug Induced Diseases- Diseases which are induced by drug that are fall
in this category. Drug may induced diseases due to following factors:
1. Overdose
2. Drug Interactions
3. Secondary Effects
4. Idiosyncrasy
5.Hypersensitivity
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

9. ➢ Overdose: Pharmacokinetics parameters (ADME) can change into a sub
therapeutic dose or overdose. Dose-related adverse reactions can occur because of
variations in the Pharmaceutical, Pharmacokinetic, or Pharmacodynamic
properties of a drug, often due to Pharmacogenetic characteristic of a patient.
➢ Ex- out-dated Tetracycline can cause Fanconi’s Syndrome.
➢ Drug -Drug interactions: When one drug is given combinable with the other
there may interaction of both the drug whether it is pharmacokinetically &
pharmacodynamically.
➢ Secondary Effects: “Any effects which can associated with a drug besides the
desired”
OR
“Indirect consequences of a primary action of the drug”
Ex- Tetracyclines- suppression of bacterial flora- superinfections
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AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA

10. ➢ Idiosyncrasy: Simply abnormal drug response. Genetically determined
abnormal reactivity to a chemical.
Ex- Chloramphenicol- Rarely causes aplastic anemia in some
individuals.
• It occur in generally abnormal subjects.
➢ Hypersensitivity: Ex- Penicllin induced hypersensitivity. It is an
allergic reaction which occur after second or absequent exposure of drug
causing ‘Allergy’.
➢ Allergic reaction is no relationship to the usual pharmacological effects of
the drug.
➢ The illness is often recognizable as a form of immunological reaction like
rash, serum sickness, urticaria etc.
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11. ➢ Drug allergy further classify into 4-major forms- (Type I-IV)-
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Type I Reactions
(Anaphylaxis/
immediate
hypersensitivity)
• Ex- Penicillins,
Streptomycin
Type II Reactions
(Cytotoxic Reactions)
•Ex.Thrombocytopeni
a; Haemolytic
Anaemia
Type III Reactions
(Immune Complex
Reactions)
•Penicillins
Type IV Reactions
(Cell Mediated)
•Dermatitis caused
by local anesthetic
creams.
* Note: Pseudo Allergic Reactions- Term applied to reactions that resemble allergic
reactions clinically but for which no immunological basis can be found.

12. Drug Interactions-
➢ Drug interaction is defined as the pharmacological activity of one drug is
altered by the concomitant use of another drug or by the presence of some
other substance.
➢ Drug interaction are an increasingly important cause of adverse drug reactions
(ADR) & it is vital that pharmacist have a sound understanding of the issue.
➢ Pharmacist can apply knowledge of pharmacology should be recognized and
appreciated.
➢ The Drug whose Activity is effected by such an Interaction is called as a
“Object drug.”
➢ The agent which precipitates such an interaction is referred to as the
“Precipitant”.
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ARTONI, AGRA, UP, INDIA
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13. AGRA PUBLIC PHARMACY COLLEGE,
ARTONI, AGRA, UP, INDIA
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TYPES OF DRUG INTERACTIONS
1. Drug-drug
interactions
2. Drug-food
interactions. 3. Chemical-drug
interactions.
4. Drug-laboratory
test interactions.
5. Drug-disease
interactions.
❑Mostly undesirable
❑Rarely desirable(beneficial): for eg.,enhancement of activity of penicillins when
administered with probenecid.

14. Mechanism of Drug Interactions-
The 3- mechanisms by which interaction can present in body are-
❑Pharmacokinetic Interaction
❑Pharmacodynamic Interaction
❑Pharmaceutical Interaction
Pharmacokinetic Interactions
➢ These interactions are those in which ADME properties of the object drug is
altered by the precipitant and hence such interactions are also called as ADME
interactions; these are classifies as
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Absorption
interactions Distribution
interactions
Metabolism
interactions
Excretion interactions

15. ➢ Absorption interactions: Are those where the absorption of the object
drug is altered. The net effect of such an interaction is-
➢ Faster or slower drug absorption.
➢ More, or, less complete drug absorption.
The major mechanisms of absorption interactions are:-
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1. Complexation and adsorption
2. Alteration in GI pH
3. Alteration in gut motility
4. Inhibition of GI enzymes.
5. Alteration of GI micro flora
6. Malabsorption syndrome

16. ➢ Distribution interactions:
➢ The major mechanism for distribution interaction is alteration in protein-drug
binding.
Ex- Anti coagulants + Phenylbutazone, chloral hydrate- Increased clotting time-
increased risk of hemorrhage.
➢ Metabolism Interactions:
➢ Are those where the metabolism of the object drug is altered. They include-
➢ Enzyme induction: Increased rate of metabolism
➢ Enzyme inhibition: Decreased rate of metabolism. It is the most significant
interaction in comparison to other interactions and can be fatal.
➢ Excretion Interactions:
➢ Are these where the excretion pattern of the object drug is altered. Major
mechanisms of excretion interactions are-
➢ Alteration in renal blood flow
➢ Alteration of urine PH
➢ Competition for active secretions
➢ Forced diuresis
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ARTONI, AGRA, UP, INDIA
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17. Pharmacodynamic interactions:
➢ Are those in which the activity of the object drug at its site of action is altered by
the precipitant. Such interactions may be direct or indirect.
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ARTONI, AGRA, UP, INDIA
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Direct Pharmacodynamic
interactions.
Indirect Pharmacodynamic
interactions
Direct pharmacodynamic Interactions: 3- interactions are-
Antagonism
Addition or summation Synergism or potentiation

18. ➢ Antagonism:
➢ The interacting drugs have opposing actions. Ex- Acetylcholine and noradrenaline
➢ Addition or summation:
➢ The interacting drugs have similar actions and the resultant effect is the some of
individual drug responses. Ex- CNS depressants like sedatives and hypnotics
➢ Synergism or potentiation:
➢ It is an enhancement of action of one drug by another. Ex- Alcohol enhances the analgesics
activity of aspirin.
Indirect pharmacodynamic interaction:
➢ In which both the object and the precipitant drugs have unrelated effects. But
the latter in Some way alerts the effects but latter in some way alerts the
effectsof the former.
Ex- salicylates decrease the ability of the platelets to aggregate thus impairing the Homeostasis if
warfarin induced bleeding occurs.
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19. Pharmaceutical interactions:
➢ Also called as incompatibility. It is a physicochemical
interaction that occurs when drugs are mixed in i.v . Infusions
causing precipitation or inactivation of active principles .
➢ Ex- Ampicillin ,chlorpromazine & barbituates interact with dextran in
solutions and are broken down or from chemical compounds.
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