Factors Modifying Drug Action_Adverse Drug Effects_Drug Interactions and Bioassay of Drugs

1. Factors Modifying Drug Action,
Adverse Drug Effects,
Drug Interactions and
Bioassay of Drugs
An Assignment On

2.  Presented By :- 5th Sem, B.F.Sc
• Bheda Nehal B.
• Chaudhari Parimal R.
• Chudasama Rajesh V.
• Khalasi Binal R.
• Khalasi Yash A.
• Modi Jhanvi A.
Subject : Pharmacology (AHM 301)
Prof. Mihir R. Patel
Assistant Prof., COF, NAU
Dr. Haresh G. Solanki
Assistant Prof., COF, NAU

3. I. Physiological Factors
II. Pathological Factors
III. Genetic Factors
IV. Environmental Factors
V. Interaction with other drugs
FACTORS MODIFYING DRUG ACTION

4. I. Physiological Factors
• Age
• Sex
• Body weight
• Food

5. • AGE
Newborn
↓
gastric acid secretion.
↓
liver microsomal enzymes (glucuronyl transferase).
↓
Plasma protein binding.
↓
GFR & tubular secretion.

6. • SEX
 Testosterone increases the rate of biotransformation of
drugs.
 Decreased metabolism of some drugs in female
(Diazepam).
 Females are more susceptible to autonomic drugs
( estrogen inhibits choline estrase).

7. II. Pathological Factors
Diseases cause individual variation in drug response
↓ Plasma protein binding for warfarin,
tolbutamide → adverse effects.
↓ Hepatic blood flow → clearance of morphine-
propanolol.
 Impaired liver microsomal enzymes
↓ Diazepam-rifampicin-theophylline

8. III. Genetic Factors
 The existence in a population of two or more
phenotype with respect to the effect of a drug.
e.g. Acetylation enzymes deficiency

9. IV. Environmental Factors
- Temperature
- Light
- Humidity
- Pollution

10. Undesirable or harmful effects which can occur at
therapeutic doses and need a reduction of dose
or drug withdrawal .
• Nausea and vomiting
• Deafness with gentamycin
• Death with penicillin
ADVERSE DRUG EFFECTS

11. Types of adverse drug reactions
A, B, C, D and E
1) Type A reactions
– Excessive therapeutic effect
– Side effects

12. Cont....
– Common
– 75 % of all adverse reaction
– Related to pharmacological actions
– Dose-dependent
– Predictable
– Can be avoided by adjusting the dosage regimen
– Most of them are reversible upon stopping drug
Example:
Hypotension (anti hypertensives)
Hypoglycemia (insulin)

13. Cont....
1. Excessive therapeutic effect:
 Unwanted effects related to the main
pharmacological actions of the drug that
occur when the drug produce greater
therapeutic effect than is necessary.
• Warfarin → Anticoagulant → Bleeding
• Insulin → Normoglycemia → Hypoglycemia

14. 2. Side Effects:
• Unwanted effects unrelated to the main
pharmacologycal action of the drug but due
other normal actipon of the drug.
• Example:
Morphine causes constipation during
its use as a analgestic.

15. 2) Type B reactions
– Not related to the normal pharmacological
actions of the drug.
– Unpredictable
– Not dose-related.
– Occur only in minority of patients.

16. Types
– Allergic reactions (Hypersensitivity )
– Genetic disorders (Idiosyncrasy)
1.Hypersensitivity (Allergic reactions)
• Abnormal response to the drug due to antigen
antibody reactions e.g. Penicillin
• Allergic response to a drug

17. 2. Idiosyncrasy (Genetic Disorder)
It is abnormal response to the drug due to genetic
disorders.
• Succinylcholine apnea
• Malignant hyperthermia
• Porphyria

18. 3) Type C reactions (Continuous reaction)
– Due to long term use e.g. NSAIDs (Nonsteroidal
Anti-inflammatory Drugs) analgesic
nephropathy

19. 4) Type D reactions (Delayed adverse
reactions)
Carcinogenesis
Ability of some substances to induce cancer.
e.g. Stilbesterol → adenocarcinoma of vagina in
female off springs.

20. 5) Type E reactions (Ending of drug)
• Sudden discontinuation (abrupt withdrawal).
• Rebound adrenal insufficiency
e.g. Corticosteroids

21. Photosensitivity
• Photoallergic drug or its metabolite induces a cell
mediated immune response which on exposure to
light of longer wave lengths (320- 400 nm, UV) .
• Drugs involved are sulfonamides, sulonylureas,
griseofulvin, chloroquine, chlorpromazine.

22. • It is the modification of the effect of one drug
(the object drug ) by the prior or concomitant
administration of another (precipitant drug).
DRUG INTERACTION

23. Outcomes of drug interactions
1) Loss of therapeutic effect
2) Toxicity
3) Unexpected increase in pharmacological activity
4) Beneficial effects e.g. additive & potentiation
(intended) or antagonism (unintended).
5) Chemical or physical interaction
e.g. IV incompatibility in fluid or syringes mixture

24. Drug interactions before administration
• Certain drugs react with each other and get inactivated if their
solutions are mixed before administration.
• In practical situations, these in vitro interactions occur when
injectable drugs are mixed in the same syringe or infusion bottle.
Some examples are:
1. Penicillin G or ampicillin mixed with gentamicin or
another aminoglycoside antibiotic.
2. Thiopentone sodium when mixed with succinylcholine
or morphine.
3. Heparin when mixed with penicillin/
gentamicin/hydrocortisone.
4. Noradrenaline when added to sodium bicarbonate
solution.

25. • In general, it is advisable to avoid mixing of
any two or more parenteral drugs before
injecting.

26. • A bioassay is an analytical method to determine
concentration or potency of a substance by its effect
on living cells or tissues.
• Bioassays are used to estimate the potency of agents
by observing their effects on living animals (in vivo)
or tissues (in vitro).
• A bioassay experiment can either be qualitative or
quantitative, direct or indirect.
DRUG BIOASSAY

27. • Bioassay is used to detect biological hazards or
give a quality assessment of a mixture.
• Bioassay is often used to monitor water quality
and also sewage discharge and its impact on
surrounding.
• It is also used to assess the environmental impact
and safety of new technologies and facilities.

28. Methods of Bioassay for Agonists
• The drugs producing quantal effect can be
bioassayed by End point method.
• The drugs producing graded responses can be
bioassayed by
(1) Matching or bracketing method
(2) Graphical method.

29. 1. End Point Method:
• Here the threshold dose producing a positive effect is
measured on each animal and the comparison between the
average results of two groups of animals (one receiving
standard and other the test) is done.
Conc. of Unknown = Threshold dose of the Standard
Threshold dose of the Test
X Conc. of Std.

30. 2. Matching Method:
• In this method a constant dose of the test is bracketed by
varying doses of standard till the exact match is obtained
between test dose and the standard dose.
• Initially, two responses of the standard are taken. The doses
are adjusted such that one is giving response of approximately
20% and other 70% of the maximum.
• The response of unknown which lies between two responses
of standard dose is taken.
• The panel is repeated by increasing or decreasing the dose s
of standard till all three equal responses are obtained.

31. • The dose of test sample is kept constant. At the end, a
response of the double dose of the standard and test which
match each other are taken. These should give equal
responses. Concentration of the test sample can be
determined as follows:
Conc. of Unknown =
Dose of the Standard
Dose of the Test
X Conc. of Std.

32. 3. Graphical method:
• This method is based on the assumption of the dose-response
relationship.
• Log-dose-response curve is plotted and the dose of standard
producing the same response as produced by the test sample
is directly read from the graph. In simpler design, 5-6
responses of the graded doses of the standard are taken and
then two equiactive responses of the test sample are taken.
The height of contraction is measured and plotted against the
log-dose.
• The dose of standard producing the same response as
produced by the test is read directly from the graph and the
concentration of test sample is determined by the same
formula as mentioned before.

33. Thank You