Pharmacokinetics and Pharmacodynamic- General Pharmacology Ravinandan A P - 2. Delivered a guest lecturer on “Pharmacokinetics and Pharmacodynamics” in Continuing Medical Education (CME) program, organized by Taluk Doctor’s Association Chalkere Taluk, Chitradurga District, Karnataka on 28th Sep 2010.

1. Pharmacokinetics
&
Pharmacodynamics
Ravinandan A P
Clinical Pharmacist & Lecturer
Department of Pharmacy Practice
SJM College of Pharmacy &
Basaveshvara Medical College Hospital & Research Centre,
Chitradurga

2. Presentation outlines
1. What is Pharmacology?
2. Divisions of pharmacology
3. Pharmacokinetic ?
4. Pharmacodynamics ?
5. Conclusion

3. What is Pharmacology???
It is derived from Greek i.e.,
Pharmacon-Drug, logos- discourse
in/study.
It is the science of “DRUGS”
It consists of detailed study of drugs,
particularly their actions on living
animals, organs or tissues.
 The action may be beneficial or
harmful.

4. Presentation outlines
1. What is Pharmacology?
2. Divisions of pharmacology
3. Pharmacokinetic ?
4. Pharmacodynamics ?
5. Conclusion

5. What are the two main divisions of
Pharmacology?
Pharmacokinetic Pharmacodynamics

6. Pharmacokinetic means what ?
Pharmacokinetics (in Greek:
“pharmacon” meaning drug and
“kinetikos” meaning putting in
motion.

7. Presentation outlines
1. What is Pharmacology?
2. Divisions of pharmacology
3. Pharmacokinetic ?
4. Pharmacodynamics ?
5. Conclusion

8. Pharmacokinetics
Absorption Distribution Metabolism Excretion
• movement of drugs in the body
• what the body does to the drug

10. Bound Free Free Bound
LOCUS OF ACTION
“RECEPTORS”
TISSUE
RESERVOIRS
SYSTEMIC
CIRCULATION
Free Drug
Bound Drug
ABSORPTION EXCRETION
BIOTRANSFORMATION

11. GI Absorption
Blood
Renal
excretion
Pharmacokinetics
Extracellular
compartment
of tissues
Oral ingestion

12. The structure of cell membrane？
How to transport it？

13. The other forms of passive transport
Filtration:
water solubility
small molecular
Facilitated transport：
 （in fact it is a kind of passive transport）
 Transport from high concentration to low
concentration
Not requiring energy
Requiring carriers
eg the absorption of Vitamin B12 from GI tract
The transportation of Glucose to the intra cellular
membrane of red blood cells.

14. Active transport
 permeating membrane from lower
concentration to higher concentration.
 Requiring energy
 Requiring carriers
 Be Saturable
 H aving competitive inhibition
Such as : peptide, amino acid

15. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport

16. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport

17. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport

18. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport

19. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport

20. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport
Sugars, amino
acids, vitamins

21. Diffusion
Active Transport
Bulk Flow
Endocytosis
Ion Pair
Facilitated Transport
Most drugs are
absorbed and
distributed by
diffusion.

22. Primary aspects of PK ?
1. To determine the frequency of
administration of drug.
2. To ascertain the duration of
effective action of drug.
3. To predict the onset of desired or
undesired effects of drugs.

23. The disposition to drugs by living
systems can be divided into four related
duration:
（Absorption）
（Distribution）
（Metabolism）
（Excretion）
ADME
Metabolism + Excretion = Elimination
Absorption + Distribution + Excretion =
Transportation
Metabolism= Transformation

24.  Absorption is the transfer of a drug from its
site of administration to the blood stream.
Characters：
Most of drugs are absorbed by the way of
passive transport.
 Intravenous administration has no
absorption.
 The absorptive speed affects the time of
appearing effect.
The absorptive extent affects the intensity of
action.

25. Factors affecting absorption:
 drug properties:
particle size, lipid solubility, Molecular weight
etc.
 Routes of Administration (important):
Enteral; parenteral
 Other:
Blood flow to the absorption site;
Total surface area available for absorption
Contact time at the absorption surface
Affinity with special tissue
Concentration of drug
Disease conditions
Functional state of GIT

26. Distribution
Drug distribution is the process by
which a drug reversibly leaves the
blood stream and enters the
interstitium (extracellular fluid)
and/or the cells of the tissues.

27. 药物的体内过程 分布
•Factors affecting drug distribution：
•Blood flow
•Capillary permeability
•Capillary structure
•Drug structue
•Binding of drugs to proteins
•Most drugs found in the vascular compartment
are bound reversibly with one or more of the
macromolecules in plasma.
•Many acidic drugs bind principally to albumin，
while basic drugs frequently bind to other
plasma proteins such as lipoproteins and α1-
acid glycoprotein (α1-AGP)。

28. （Protein binding）
Characters：
Drugs ordinarily bind to protein in a reversible fashion
and in dynamic equilibrium. Those bound to protein are
called bound drug, and those unbound to protein are
called free drug.
Only the unbound drugs can diffuse through the
capillary wall, produce its systemic effects, be
metabolized and be excreted.
Bound drugs lose pharmacological activity momentarily，
and act as a drug reservoir.
Having saturation and competitive inhibition.
Patient with low plasma protein (uraemia,
hepatic disease) or old people with low
albumin in plasma ,their percentage of
protein binding may be changed, amount of
unbound drug increases, effect precipitate.

29. interaction
When the two kind of drugs that
possess the higher protein binding rate are
associated for clinical using, the drug
interaction may occur.
If the amount of unbound drug displaced
from plasma protein increases, the unbound
drug concentration and effect also
increases, and perhaps, produce toxicity.
Such as: phenylbutazone
Dicoumarin

30.  Metabolism：
Alteration of drug within a living organism, so as to
modify its activity or its nature.
The liver is the major site for drug metabolism.
Changes after metabolism:
The pharmacological activity of the drugs is
decreased or lost, while certain drugs must metabolize
to exert the reaction.
Two phase of metabolism:
Phase I：oxidation (氧化) 、hydrolysis,
reduction.
Phase Ⅱ：conjugation： glucuronic acid ,
sulfuric acid.

32. Variety of drug activity after
biotransformation:
A active drug inactive metabolites
B inactive drug active/enhanced activity
Such as : P-450
Cyclophosphamide
blood tumor
aldophosphamide
Phosphamide mustard

33. C active drug active product
Phenacetin
Acetaminophen (paracetamol)
(prototype drug or parent drug)

34. D no toxic or less toxic drug toxic
metabolites
Isoniazid Acetylisoniazid
INH Acetyl INH
mutagenicity
teratogenicity
carcinogenicity
hepatotoxicity

35. Excretion
Principal organs：
Kidney，biliary system, lungs, intestines, milk,
skin, sweat glands, tear.
• Excretion is a transport procedure which
the prototype drug (or parent drug) or other
metabolic products are excreted through
excretion organ or secretion organ.

36. Renal Excretion
Filtration
Secretion
Reabsorption

37. Renal excretion
glomerular filtration
Protein bound drugs are not
filtered !!
Reabsorption
high lipid-soluble ,lower polar.
unionized drug easy to reabsorb
high water–soluble, high polar
ionized drug uneasy to reabsorb
Active secretion of tubule
Changing pH of tubular lumen
fluid, may change absorption
extent of drug in urine.

38.  acidic urine =
alkaline drugs eliminated
acid drugs reabsorbed
alkaline urine =
- acid drugs eliminated
- alkaline drugs absorbed
renal disease/ decreased clearance
affects drug dosage

39. Affect of uric pH on dissociation of drug
weak acid drug alkaline urine
dissociation large excretion accelerate
weak basic drug acid urine
dissociation large excretion fast
weak acid drug acid urine
dissociation small excretion reduce
weak basic drug alkaline urine
dissociation small excretion slow

40. for example :
Streptomycin 0.5g Q6H
High concentration in urine fluid .
100 time higher in urine than in blood .
Treatment inflammation in uric tract.
Sulfonamides in acid urine
Concentration
Crystallization

41. Presentation outlines
1. What is Pharmacology?
2. Divisions of pharmacology
3. Pharmacokinetic ?
4. Pharmacodynamics ?
5. Conclusion

42. Pharmacodynamics
Greek: dynamic-power
What the drug does to the body.
It describes the biochemical and
physiological effects of drugs and
their mechanism of action.

43. Principles of drug action
1. Stimulation
2. Depression
3. Irritation
4. Replacement
5. Cytotoxic actions

44. Actions of Drugs
Drugs that act by binding to a
receptor site
Drugs that act by changing physical
properties
Drugs that act by chemically
combining with other substances
Drugs that act by altering a normal
metabolic pathway

45. Side effect
Unintended response to a drug
Allergic reaction
Hypersensitivity
Idiosyncrasy
Drug effect unique to an individual
Cumulative effect
Increased effectiveness when a drug is given in
several doses.

46. Tolerance
Decreased response to the same amount
Tachyphylaxis
Rapidly occurring tolerance to a drug

47. Drug dependence
The patient becomes accustomed to the drug’s
presence in his body.
Drug interaction
The effects of one drug alter the response to
another drug.
Drug antagonism
 The effects of one drug block the response to another
drug.
Potentiation
One drug enhances the effect of another.

48. Summation
Also known as additive effect. Two
drugs with the same effect are given
together—similar to 1+1=2.
Synergism
Two drugs with the same effect are
given together and produce a response
greater than the sum of their
individual responses—similar to 1+1=3.

49. Factors Affecting Drug Response
Age
Body mass
Sex
Environment
Time of
administration
Pathology
Genetics
Psychology

50. Drug Interactions
Drug interactions occur whenever
two or more drugs are available in
the same patient.
The interaction can increase,
decrease, or have no effect on
their combined actions.

51. Presentation outlines
1. What is Pharmacology?
2. Divisions of pharmacology
3. Pharmacokinetic ?
4. Pharmacodynamics ?
5. Conclusion

52. Conclusions
 Pharmacology is a the science which deals
with the action of drugs on a living organism,
its organs or tissues.
PK is a part of pharmacology which deals
with ADME.
PD is the study of biochemical and
physiological effects of drugs and their
mechanism of action.