This presentation briefly covers the general aspect of therapeutics and drug development then its dose adjustment according to the pt. need and checking either patient comply to that therapy or not. last portion based on herbal supplements and its use.

1. Principles of Therapeutics
Indiviualization of Dosage
Compliance
Herbal/Botanical Suppliments
Faraza Javed
Mphill Pharmacology

2. Therapeutics
The treatment and care of a patient for the purpose of
both preventing and combating disease or alleviating
pain or injury. The term comes from the
Greek therapeutikos, which means “inclined to serve.”
OR
The branch of medicine concerned with the treatment
of disease.

3. Drug
A chemical substance of known structure, which, when
administered to a living organism, produces a
biological effect.

4. Most common parameters evaluated to check the action
and therapeutic activity of the drug.
Pharmacodynamic
Pharmacokinetics
Preclinical Study
Clinical Trials

5. Pharmacodynamics

6. Pharmacodynamics
Study of how drug act on living body.
How drug act…
General Principles: Binding Postulate
Such binding leads to cellular response that results in
pharmacological effect of drug.

7. How Drugs Act: GeneralPrinciples
The Binding Postulate
Paul Ehrlich
“A drug will not work unless it is bound”

8. Drug Targets
Receptor
s
Enzyme
s
IIon
Channels
Carrier
Molecule
(Transpo
rter)
Miscellaneou
s

9. Receptors
The cellular Assembely which recognizes chemical mediators.
Binding Activation
Chain of
Reaction
Physiological
Action
Affinity Efficacy

10. Enzymes

11. Ion Channels

12. Transporter

13. Miscellaneous:
Drugs that act without being bound to any tissue
constituent (e.g. osmotic diuretics, antacids and heavy
metal chelating agents) may fall in this category.
A few other types of protein (plasma proteins) are
known to function as drug targets and their exist many
drugs with sites of action that are not yet known. e.g
Nefopam.

14. Pharmacokinetics

15. Pharmacokinetics
Absorption
Distribtion
Metabolism
Excretion

17. Bioassays and Clinical Trials

19. Bioassay
Biological testing procedure for estimating the
concentration of a pharmaceutical drug substance
in a formulated drug product or bulk material.
The specific potency of drug is given to animal and
then drug response is compared with the
standards.

20. Objective
Bioassays are commonly applies to characterised:
Substance Biological Properties
To study a Biological Process
To detect the presence and quantity of a substance in a
sample
To screen for active molecules from a library of
molecules

22. Clinical Trials

23. Clinical Trials
A rigorously controlled test of a new drug or a new
invasive medical device on human subjects; it is
conducted under the direction of the FDA before
being made available for general clinical use.

24. Phases of Clinical Trials
Phase I
Phase II
Phase III
Phase IV

25. Phase I
The object of the first clinical
trials in humans is to find out
if the new drug is safe.
These first trials, called "Phase 1“
trials, usually involve a small
number of individuals
(less than 100) who are healthy.

26. Phase II
This second phase of testing
may last from several months
to 2 years, and involve up to
several hundred patients.
Most Phase 2 studies are
randomized trials. One group
of patients will receive the
experimental drug, while
a second "control" group will
receive a standard treatment
or placebo. Often these studies
are "blinded"--neither the patients
nor the researchers know who is
getting the experimental drug.

27. Phase II trials are aimed at elucidating dose
response relationships, safety and efficacy of the
compound treating the disease or condition for
which it is intended.

28. Phase III
In a Phase 3 study, a drug is tested in several
hundred to several thousand subjects. This large-
scale testing provides more information about the
drug's effectiveness, possible side effects, and
safety in a broader range of people.

29. Phase IV
Phase IV trial is also known as postmarketing
surveillance Trial. Phase IV trials involve the safety
surveillance and ongoing technical support of a drug
after it receives permission to be sold.
Harmful effects discovered by Phase IV trials may result
in a drug being no longer sold, or restricted to certain
uses. Recent examples involve Cerivastatin (brand
names Baycol and Lipobay), Troglitazone (Rezulin)
and Rofecoxib (Vioxx).

30. Indiviualization of Drug
Therapy OR
Dosage Indiviualization

31. Dosage Indiviualization
Adaptation of the dosage regimen in function of clinical
characteristics of the indiviual aiming to achieve the
best possible therapeutic efficacy at the lowest risk of
unwanted side effects.

32. Factors
Factors responsible for variation in drug response:
Ethinicity
Age
Genetic Factor
Idiosyncratic Reactions
Disease
Drug Interaction

33. Ethnicity
“Pertaining to Race”
Examples:
African-American with heart failure gain a mortality
benefits from treatment with a combination of
Hydralazine+Nitrates whereas White Americans do
not.
Overal effectiveness of Gefitinib in treating patients
with advanced lung cancer has been disappointing but
in 10% of patients, lung tumor shrinks rapidly.
Japenese patients are 3 times as likely as whites to fall
into this group.

34. Age
The main reason that age effect drug action is that
elimination is less efficient in new born babies and in
old people hence drug produce greater or prolonged
effect.

35.  Other age related factor like Physiological
factors(altered CV reflexes) and Pathological
factors(Hypothermia, common in elder people) also
influence drug effect.
Fat contributing a greater proportion to body mass in
elderly with consequent changes in distribution
volume of drug.

36. Effect of Age on Renal
Excretion of Drug
Gentamycin has a plasma half life of 18 hours or greater
in new born as compared with 1 to 4 hours for adults.
It is therefore necessary to reduce the doses to avoid
toxicity.

37. Drugs Neonates Adults Elders
Gentamycin 10-18 2 4
Digoxin 200 40 80
Diazepam 25-100 15-25 50-150
Mean Half Life of some Drugs(h)

38. Genetic Factors/Pharmacogenomics
The study of genetic variation that influence indiviual
response to the drug.
Cytochrome P450(CYP) Genes

39. Clopidogrel(Plavix)
R
It is a Platelet inhibitor used in the treatment of no.
of CV diseases. However, despite of Clopidogrel
treatment, upto one quarter of patients experience
a sub therapeutic antiplatelet response, resulting
in higher risk for an ischemic event.
Clopidogerl is a prodrug, its antiplatelet properties
exerted once it is converted to an active
metabolite. A Cytochrome P450 enzyme CYP2C19
mediate the conversion of clopidogrel into its
active metabolite.

40. Patients who carry certain variations in CYP2C19 are
considered poor metabolizer and show decreased
ability to convert clopidogrel into its active metabolite
resulting in a diminshed antiplatelet effect.
Hence Patient are more likely to have an ischemic
event following clopidogrel therapy.
Approx. 2-20% of patients are likely to carry CYP2C19
variations.

41. Idiosyncratic Reactions
An IR is abnormal and usually harmful drug effect that
occurs in a small proportion of individuals.
Reaction may occur with low doses
Genetic factor may be responsible
Cause is poorly understood

42. Examples
Chloramphenicol causes Aplastic Anemia in approx. 1
in 50,000 patients.
Primaquine, Dapsone, Doxorubicin and some
Sulfonamide cause Hemolysis leading to severe anemia
in 5-10% of Afrocarribean men.

43. Effect of Diseases
Impaired Renal or Hepatic function predispose to
toxicity causing unexpectedly intense or prolonged
drug effect as a result of increased drug conc.
Hypothermia markdely reduce the clearance of many
drug.

44. Drug Interactions
Polypharmacy in case of chronic diseases may interact
and results in toxicity.
The risk of bleeding specially from stomach caused by
Warfarin is increased by drugs that cause bleeding by
different mechanism like Aspirin.
Sulfonamide prevent the synthesis of folic acid by
bacteria and other MCOs. Trimethoprim Inhibits its
reduction to THF. Given together, drugs have
synergistic action in treatig Pneumocystis carinii.

45. Compliance

46. Compliance
It is the act of taking medication on schedule or taking
medication as prescribed.

47. Resons for Medication Non
Compliance

48. Outcomes
Unnecessary disease progression and complication
Reduced functional abilities and quality of life
An additional medical cost and physician visit

49. Botanical and Nutritional
Suppliments

50. Botanicals
Botanicals are plant preparations which have become
widely available in the form of food suppliments.
Examples:
Ginkgo
Green Tea
Ephedra
St. John Wort
Ginseng

51. Natural does not mean It is Safe!
Botanicals are safe.. Consumer tend to believe that
because they are natural, Botanicals are safe. But
interaction b/w herbal substances and conventional
drugs have been reported.

53. Green Tea
Green Tea has a relationship
with metabolism of lipids.
It is a natural and useful aid
to maintain normal body
weight. It regulate cholesterol
and boost your immunity.

54. Ginkgo(Ginkgo Biloba)
Ginkgo has been used to treat
circulatory disorders and enhance
memory, specially effective in
treating Dementia. Studies have
shown that ginkgo improves blood
circulation by dilating blood vessels
and reduce the platelet activity.

55. Hence, Ginkgo may increase the effect of some blood
thining medicine including Aspirin. People taking
blood thining medication should ask their doctors
before using Ginkgo.

56. St. John’s Wort(Hypericum Perforatum)
Well known for its
anti-depressent effect.
Effective treatment for mild
to moderate depression.
Interact with a variety of
medications including antivirals.
Take it only under the guidance
of Health Care Provider.

57. Epedra
 Uses: Bronchial asthma, Athletic Performance
Enhancer
Likely safe in low doses for 7 days
Likely unsafe in higher doses for longer
periods, associated with MI, stroke, seizures and
death
Interact with drugs including MAO
inhibitors, SSRIs, Glycosides and Caffeine.
Banned by FDA in February 2004.

58. 140 Events, 1/3 definitely-related to supplement,
10 deaths, 10 strokes, 13 permanent disabilities

59. Conclusion
 Polypharmacy is common among supplement users
Many assume herbs and supplements are safe
Many pharmacological actions but dangerous side
effects and interactions exist

60. Future of Herbal Medicine
In some countries of Europe, herbs are classified and
regulated as drugs.
While still not widely accepted, but herbal medicine is
being taught more in medical or pharmacy schools.
Researchers will be looking at their health effects and
in particular their anti-oxidant, anti-diabetic and
memory mediating activities, which, it is hoped, will
contribute to the development of new food and
supplimentation offering a +ve effect on the
maintenance of health.

61. References
 Rang H. P., & Dale M. M. (2007). Rang & Dale’s
Pharmacology (6th Edition). London, United Kingdom.
 Katzung B. G., & Masters S. B. (2012). Basic & Clinical
Pharmacology (12th Edition). Califonrnia, San Francisco.
 Dietary Supplementation Health and Education Act of
1994.
 Natural Medicines Comprehensive Database 2006.