2. DEFINITION
MODIFICATION OF RESPONSE TO ONE DRUG BY
ANOTHER WHEN THEY ARE ADMINISTERED
SIMULTANIOUSLY OR IN QUICK SUCCESSION ie,
THE EFFECTS OF ONE DRUG ARE AFFECTED BY
THE EFFECT OF ANOTHER DRUG.
3. Severity of drug interacton in most
cases is highly unpredictable
The doctor must know which drugs are
not to be prescribed concurrently
6. PHARMACOKINETIC INTERACTIONS
These interactions alter the concentration of
the object drug at its site of action by
affecting its
absorption,distribution,metabolism or
excretion
7. ABSORPTION
Due to formation of insoluble &poorly
absorbed complexes in the gut lumen
Eg:Btw Tetracyclines & calcium/iron salts
Can be minimized by administering two
drugs with a gap of 2-3 hours
8. DISTRIBUTION
Due to displacement of one drug from its
binding sites on plasma proteins by another
drug
Eg:Quinidine & Digoxin
9. METABOLISM
Certain drugs reduce or enhance the rate of
metabolism of other drugs
Eg:Microsomal enzyme inducers like
barbiturates, rifampicin can cause
contraceptive failure
10. EXCRETION
Important in case of drugs actively secreted
by tubular transport mechanisms
Eg:Probenacid inhibits tubular secretion of
penicillins &cephalosporins and prolongs
their plasma t1/2
11. PHARMACODYNAMIC INTERACTIONS
These interactions are due to modification of
action of one drug at the target site by
another drug independent of change in its
concentration
This results in
Enhanced response-SYNERGISM
Attenuated response-ANTAGONISM
Abnormal response
12. EXAMPLES
Fall in BP & MI due to use of sildinafil by
patients receiving organic nitrates
Severe hyperkalaemia by concurrent use of
ACE inhbitors & K+ sparing diuretics
Additive ototoxicity due to use of
aminoglycoside in patient receiving
furosemide
13. DRUG INTERACTIONS BEFORE ADMINISTRATION
Certain drugs react with each other and get
inactivated if their solutions are mixed before
administration
Eg:Penicilln G/Ampicillin +Gentamicin
Thiopentone sodium+Succinylcholine
17. SIDE EFFECTS
These are undesirable effects which are
observed even with the therapeutic doses of
the drug
They are usually mild and manageable
Eg:Promethazine has antiallergic action -
Desirable effect,but it also produces sedation
in therapeutic doses-Side effect
18. SECONDARY EFFECTS
These are indirect consequences of the main
pharmacodynamic action of the drug
Eg:Development of superinfection after
suppression of bacterial flora by antibiotics
19. TOXICITY
These are exaggerated form of side effects
which occur due to overdoses or after
prolonged use of the drug
Eg:Bleeding due to high doses of heparin
21. DRUG ALLERGY[HYPERSENSITIVITY REACTIONS]
Allergic responses to drug occur when there
has been previous exposure to drug & when
this sensitised individual is re-exposed to the
same drug again
Drugs may elicit Type I,II,III & IV
Hypersensitivity reactions.
22. TYPE I HSR
Allergy develops with in minutes & lasts for 2-3 hour
Drug causes formation of tissue sensitizing IgE
antibodies that are fixed to mast cells or leucocytes.
The subsequent exposure to drug degranulates mast
cells or activates leucocytes with release of chemical
mediators [histamine,serotonin] of allergy
The patient if untreated suddenly passes into
anaphylactic shock.
Eg:Anaphylaxis after parenteral administration of
penicillin or radiocontrast media
23. TYPE II HSR
It results when a drug binds to RBC & is
recognised by IgG Ab.
The Ag-Ab reaction triggers the lysis of RBC
by complement activation /action of cytotoxic
T cell/phagocytosis by macrophages.
Results within 72 hr of drug administration
Eg:Drug induced Thrombocytopenia,SLE
after quinidine use
24. TYPE III HSR
Ag-Ab form complexes which are deposited
on vascular endothelium & activate
complement
Eg:Glomerularnephritis after giving NSAID
25. TYPE IV HSR
These reactions are mediated by sensitised
T cells following contact with an antigen
Sensitised T cells results in release of
cytokines which activate
macrophages,granulocytes & natural killer
cells
Eg:Contact dermatitis ,Photosensitivity.
26. GENETICALLY DETERMINED ADVERSE EFFECTS
Drug reactions in some individuals may be
qualitatively different from effects usually
observed from majority of subjects
The mechanism is of genetic origin
Eg:The genotype with atypical pseudocholine
esterases cannot hydrolyse
succinylcholine,in that case even the
therapeutic dose of sccinylcholine leads to
prolonged respiratory failure
27. IDIOSYNCRATIC DRUG RESPONSES
These are harmful & sometimes fatal
reactions that occur in a small minority of
individuals,for which the cause is yet poorly
understood.
Eg:Malignant Hyperthermia on using
halothane ,succinylcholine
28. TYPE –C [CHRONIC EFFECTS]
Adverse effects that are associated with
prolonged use of drug.
Eg:Cushing syndrome after chronic use of
prednisolone
29. TYPE-D[DELAYED EFFECTS]
Adverse effects that occur in patients years
after treatment or effects appearing in their
children who did not receive the treatment
Eg:Clear cell carcinoma of vagina in the
daughters of women who took
diethylstilbesterol during pregnancy
32. The placenta does not
strictly constitute a
barrier and any drug
can cross it to a
greater or lesser
extent.
33. FACTORS THAT DETERMINE THE
EFFECTS OF TERATOGENS
1. Point in development when
drug exposure occurs
2. Duration of exposure
3. Susceptibility of fetus
4. Dose reaching fetus
35. 1. Fertilization & implantation -
conception to 17 days- failure of
pregnancy
2. Organogenesis-18 to 55 days-
deformities -MOST
VULNERABLE PERIOD
3. Growth & development- 56
days onwards-developmental &
functional abnormalities.
36. MECHANISM OF TERATOGENICITY
Poorly understood
Multifactorial
1.Drugs directly affect the process
of differentiation
2.Drugs may interfere with the
passage of oxygen & nutrients through
placenta
3.Deficiency of a critical substance
38. CATEGORY -A
Controlled studies show no
risk
Adequate, well-controlled studies in pregnant
women have failed to demonstrate a risk to
the fetus in any trimester of pregnancy.
39. CATEGORY -B
No evidence of risk in humans
Adequate, well-controlled studies in
pregnant women have not shown an
increased risk of fetal abnormalities
despite adverse findings in animals,
or, in the absence of adequate human
studies, animal studies show no fetal
risk. The chance of fetal harm is
remote, but remains a possibility.
40. CATEGORY-C
Risk cannot be ruled out
. Adequate, well- controlled human studies are
lacking, and animal studies have shown a
risk to the fetus or are lacking as well. There
is a chance of fetal harm if the drug is
administered during pregnancy, but the
potential benefits may outweigh the potential
risk.
41. CATEGORY - D
Positive evidence of risk
Studies in humans, or investigational or post-
marketing data, have demonstrated fetal
risk. Nevertheless, potential benefits from
the use of the drug may outweigh the
potential risk. For example, the drug may
be acceptable if needed in a life-threatening
situation or serious disease for which safer
drugs cannot be used or are ineffective
42. CATEGORY - X
Contraindicated in pregnancy
Studies in animals or humans, or
investigational or post-marketing
reports, have demonstrated positive
evidence of fetal abnormalities or risk
that clearly outweighs any possible
benefit to the patient.
43. CLASSIFICATION BASED ON TERATOGENIC POTENTIAL
Category Characteristics Examples
A Controlled human studies
show no risk
Folic Acid
Thyroxine
B Animal studies OK no
human data
Paracetamol,
Erythromycin
C Animal studies not OK no
human Data
Rifampicin
Morphine
D Evidence for risk +++
Benefits outweigh risk
Antiepileptics
X Evidence for risk +++
Risks outweigh benefits
Thalidomide
Retinoids
45. THALIDOMIDE -A LESSON IN MEDICINE
PHOCOMELIA : THIS ABNORMALITY ('SEAL LIMBS')
CONSISTS OF AN ABSENCE OF DEVELOPMENT
OF THE LONG BONES OF THE ARMS AND LEGS
46. THALIDOMIDE
Developed in Germany in 1954
Promoted as a tranquiliser and anti emetic
Taken by thousands of pregnant women
Resulted in >10,000 children with birth
deformities
Withdrawn in 1961
Has found new uses as an immune modulator &
for multiple myeloma
47. LESSONS FROM THALIDOMIDE
The placental barrier is not effective
against most orally administered drugs
Animal teratogenic testing
can be misleading
53. YELLOW STAINING OF THE TEETH IN A CHILD EXPOSED TO
MATERNAL TETRACYCLINE IN UTERO
54. DIETHYLSTILBESTROL
In 1971, DES was
shown to cause
clear cell carcinoma,
a rare vaginal tumor
in girls and women
who had been
exposed to this drug
in utero.
59. TAKEHOME MESSAGES
Avoid all drugs during pregnancy
unless compelling reasons exist.
Folate therapy during pregnancy
can reduce spontaneous as well
as drug induced malformations.
