2. 1.Influence of pH on Drug Absorption
1. Explain the phenomenon exhibited by aspirin in this
figure.
2. How does pH influence drug absorption?
3. Give 2 examples for acidic drugs & 2 examples for
basic drugs.
pH3
Gastric
Lumen
pH7
CELL
Aspiri
n
2
3. 1) Aspirin, being an acidic drug , is largely
unionized in the acidic gastric lumen (pH
3) and crosses the surface membrane of
gastric mucosal cell (pH 7 ) where it
reverts to the ionized form from which it
is not able to escape easily. This
phenomenon is called as ‘Ion trapping’.
2) Drugs are better absorbed in their
unionised forms. Acidic drugs are largely
unionized at acidic pH where as basic
drugs are largely unionized at alkaline pH.
Hence their absorption is better in their
respective pH.
3) Acidic drugs: Aspirin, Phenobarbitone
Basic drugs : Atropine , Ephedrine,
3
4. 2.Volume of distribution
1. Define apparent
volume of
distribution(aVd).
Calculate the
volume of
distribution in the
given illustration.
2. What is the clinical
significance of aVd?
3. Give 2 examples of
drugs with large
volume of
distribution
• Total drug injected i.v
=1000mg
• Plasma concentration 50
mg/L
4
5. 1) Apparent volume of distribution (aVd) can be
defined as the volume that will
accommodate all the drug in the body if the
concentration throughout is the same as in
plasma.
Vd = Dose administered i.v / plasma
concentration
V = 1000/50 = 20 L
5
6. 2) Drugs with large volume of distribution have
low plasma concentration & high tissue
concentration. Hence their removal becomes
difficult in case of poisoning.
3) Examples : Chloroquine, Propranolol, Digoxin,
Morphine.
6
8. 1.Explain the graph
2. Give some examples for saturation kinetics.
3. Differentiate first order kinetics and zero order kinetics.
Give few examples
8
9. 1.The dose rate-Cpss (steady state plasma
concentration) relationship is linear only in
case of drugs eliminated by first order
kinetics.
For drugs which follow Michaelis Menten
kinetics (saturation kinetics), elimination
changes from first order to zero order kinetics
over the therapeutic range.
Increase in their dose beyond saturation
levels causes an increase in Cpss which is out
of proportion to the change in dose rate
2. Higher doses of drugs like Phenytoin,
Warfarin, Theophylline Tolbutamide and
Aspirin follow saturation (Michaelis menten)
kinetics.
9
10. First order kinetics(Linear
kinetics)
Zero order kinetics(Non
linear)
Constant fraction of drug is
eliminated per unit time
Constant amount of drug is
eliminated per unit time
Rate of elimination is
proportional to plasma
concentration
Rate of elimination is
independent of plasma
concentration
Clearance remains constant Clearance is more at low
concentrations and less at
high concentrations.
Half life remains constant Half life is less at low
concentrations and more at
high concentrations.
10
12. 1. Explain the graph. How the ionisation
status of the drug is modified in the
management of Barbiturate poisoning?
2. How does each process in kidney affect
the elimination of drugs in urine?
3. Name the nonspecific transporters
operating in proximal tubules that are
concerned with transport of organic
acid and bases. Mention a clinical
relevance to it.
12
13. 1) The clearance of phenobarbitone is more in Alkaline
urine and less in Acidic urine
Forced Alkaline diuresis in barbiturate
poisoning - Barbiturates are weak acids , when the
urine is alkalinised, they are ionised. This prevents their
reabsorption & facilitates their excretion in urine.
13
14. 2)
• Passive glomerular filtration- Ionised
drugs which are poorly absorbed are
excreted entirely by glomerular
filtration and are not reabsorbed.
• Active Tubular secretion- weak acids
and weak bases are actively secreted
by proximal tubules by carrier-
mediated systems
• Passive renal tubular reabsorption:
drugs may diffuse across the tubules
in either direction depending upon
the drug concentration, lipid solubility
and the pH
14
15. 3)
a) Organic acid transporter(OAT)
b) Organic base transporter(OCT)
Probenecid is an organic acid
which has high affinity for the tubular OATP.
It blocks the active transport of both
penicillin and uric acid,
but whereas the net excretion of the
Penicillin is decreased, that of the Uric acid
is increased.
This is because penicillin is primarily
secreted while uric acid is primarily
reabsorbed.
15
17. 1.What is preclinical trial and clinical trial?
2.Expand the following abbreviations
a) ICH
b) GCP
c) IND
d) NDA
3.What is pharmacovigilance?
17
18. 1) Preclinical trial comprises of studies
undertaken in animals, initially a rodent
(mouse/rat ) followed by a larger animal
(cat/dog/monkey) to expose the whole
pharmacological profile of a newly
synthesised/ identified prospective
compound.
A clinical trial is an
ethically designed investigation in human
subjects to objectively discover/ verify/
compare the results of two or more
therapeutic measures( drugs). Depending
on the objective of the study, it may be
conducted in healthy volunteers or in
volunteer patients .
18
19. 2)
ICH-International Conference on
Harmonization
GCP- Good clinical practice
IND- Investigational New Drug
NDA- New Drug Application
3) Pharmacovigilance is defined as the
continuous monitoring for unwanted
effects and other safety related aspects
of marketed drugs.
It is the science related to the detection,
assessment, understanding and
prevention of adverse effects or any
other drug related problem.
19
20. 6.Effect of tyramine on Blood pressure of
Anaesthetized dog after repeated administration
1. What dose of tyramine
has produced the
responses, 1, 2, 3& 4?
2. What is the initial (1)
response of tyramine on
BP?
3. What is the basis for
changes in the
subsequent responses
from that of the initial
one?
4. Name this phenomenon.
Fig. 9.Anesthetized Dog Blood Pressure.1, 2, 3,
4 = Responses to Tyramine, 0.3 mg/Kg, IV
bolus at 5-minute intervals.
1 2 3 4
20
21. 1. What dose of tyramine has produced the responses, 1, 2, 3& 4?
1, 2, 3, 4 = Responses to Tyramine, 0.3 mg/Kg, IV bolus at 5-minute intervals.
2. What is the initial (1) response of tyramine on BP?
Tyramine causes increase in BP. But on repeated administration response decreases
3. What is the basis for changes in the subsequent responses from that of the initial
one?
Tyramine is an indirectly acting sympathomimetic agent. It acts by releasing NA
from the presynaptic nerve ending. Because of repeated administration of
tyramine, there occurs depletion of NA. Hence there is a reduction in response.
4.Name this phenomenon.
Tachyphylaxis or acute tolerance.
21
