CLASS FOR BDS STUDENTS

1. Dr. RENJU.S.RAVI

3. DEFINITION
“The science that deals with the study
of variation in drug response due to
variation in genes “

4. PHARMACOGENOMICS
• The use of genetic information to
– guide the choice of drug &
–Dose
on an individual basis

5. Types of genetic variation
• Single nucleotide polymorphism (SNP) 
more common, less serious
• Insertion/ deletions (indels)  less common,
serious

6. Single Nucleotide Polymorphism

7. Consequences of polymorphisms
Pharmacokinetic
Variations
( involving drug
metabolism )
Pharmacodynamic
Variations
(involving drug-receptor
interactions)
Phase I Phase II

8. Pharmacokinetic Variations
PHASE I
Atypical pseudo cholinesterase
Slow hydrolysis of Succinyl choline 
prolonged apnea

9. Pharmacokinetic Variations
PHASE II
• Acetylation
• Polymorphism of N-acetyl transferase
Acetylation of Isoniazid
Fast acetylators slow acetylators
hepatotoxicity peripheral neuropathy

10. Pharmacodynamic variations
• Halothane induced hyperthermia
Abnormal ryanodine receptor on
sarcoplasmic reticulum
Genetic polymorphism
Excessive release of calcium

11. Other examples
• Precipitation of PORPHYRIA by
barbiturates
• Hemolysis due to G6PD deficiency.
• Insulin resistance due to receptor
mutations

12. IDIOSYNCRACY
• Genetically mediated abnormal reactivity to a
chemical in a small minority of individuals for
which no definite genotype has been
described.
• Cause unknown.
• Not found in majority of population.
• Aplastic anemia due to chloramphenicol

13. Applications of p. genetic knowledge
•Personalise medicine
1. To enhance effectiveness
2. Decrease ADR
3. To make clinical trials faster & cost
effective

14. LIMITATIONS
 Expensive and time consuming.
 Influence of environmental factors
 Ethical issues

16. TERMS
• Greek “teras” meaning "malformation”
• Teratogen: Any chemical, substance, or
exposure given to the pregnant mother
that may cause birth defects to the
developing fetus.
• Teratogenesis: The formation of an abnormal
embryo.

17. Teratogenicity
• It refers to capacity of a exogenous agents to
cause foetal abnormalities when administered
to the mother at any stage of pregnancy.
• The placenta does not strictly constitute a
barrier and any drug can cross it to a greater
or lesser extent.

18. Factors That Determine the Effects of
Teratogens
• Dose reaching fetus
• Time of pregnancy during which drug
exposure occurs
• Duration of exposure

19. Effects of Teratogens on the Fetus
Spontaneous abortion
Malformations (major or minor)
Intrauterine growth retardation
Mental retardation
Carcinogenesis
Mutagenesis (causing genetic mutation)

20. COMMON TERATOGENS

21. Effect of drugs on fetus during
pregnancy
• Fertilization & implantation
conception to 17 days- Failure of pregnancy
• Organogenesis
18 to 55 days- Congenital malformations
• Growth & development
56 days onwards-Developmental & functional
abnormalities.
Most
vulner
able
period

22. United States FDA
Pharmaceutical Pregnancy Categories
A Controlled human studies show no risk Inj MgSO4
Thyroxine
B
No confirmatory evidence of risk in
humans
Penicillin
Paracetamol
C Risk cannot be ruled out
Morphine
codiene
D Positive evidence of risk
Phenytoin
valproate
X Contraindicated in pregnancy isotretinoin

23. THALIDOMIDE
PHOCOMELIA : 'seal limbs'
Consists of an absence of development
of the long bones of the arms and legs

24. • Tetracyclines  staining of teeth
• Androgens  musculaniasation of female
fetus
• Lithium  Ebstein’s anomaly
• Phenytoin  Fetal Hydantoin syndrome
• Alcohol  Fetal Alcohol syndrome
• Valproate  Neural tube defects

25. PHENYTOIN - Fetal Hydantoin syndrome
• Cleft lip/palate
• Microcephaly
• Mental retardation

26. VALPROATE- NEURAL TUBE DEFECTS

27. ISOTRETINOIN
Mental retardation and
learning disabilities
Eye & ear deformities
Cleft lip, cleft palate & other
facial abnormalities
Heart defects
Microcephaly & Hydrocephaly

28. FETAL ALCOHOL SYNDROME

29. FETAL WARFARIN SYNDROME
• Saddle nose
• Retarded
growth
• Defects of
limbs, eyes
and central
nervous
system

30. Tetracycline- Teeth and bone damage
• Yellow staining
• Enamel hypoplasia
• Caries and pigmentation
of permanent teeth

31. Counseling women about teratogenic
risk
• The baseline teratogenic risk in pregnancy (ie,
the risk of a neonatal abnormality in the
absence of any known teratogenic exposure)
is about 3%.
• It is also critical to address the maternal-fetal
risks of the untreated condition if a
medication is avoided.

32. Summary
• Pharmacogenetics is the study of variation in
drug response due to genetic variation
• Genetic variations can lead to decreased drug
response or enhanced toxicity
• So study of Pharmacogenetics is important
• Teratogenicity- Fetal abnormalities caused by
exogenous agents
• Most vulnerable period- organogenesis
• Patient education and Proper selection of drugs