1. How to choose p(personal) drugs?
Dr. Jarir At Thobari, DPharm. PhD
Department of Pharmacology & Pharmacotherapy, Fac. Medicine UGM

2. Objectives Objectives:
be able to count dimensions which are important in drug selection
be able to explain the method in preparing a personal-drug (p-drug) list
believe in the importance of rational prescription
be able to develop own p-drug list

3. P-Drug Concept
P-drugs are the drugs you have chosen to prescribe regularly, and with whom you have become familiar
They are your drugs of choice for given indications
The P-drug concept is more than just the name of a pharmacological substance, it also includes the dosage form, dosage schedule and duration of treatment

4. P Drug Concept
P-drugs enable you to avoid repeated searches for a good drug in daily practice.
As you use your P-drugs regularly, you will get to know their benefits and side effects thoroughly.
P-drugs are your drugs of first choice for a common condition.

5. A P-drug is a drug that is
Remember that….
A P-drug is a drug that is
ready for action!

6. Rational prescription
“ Rational use of drugs requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time and at the lowest costs to the community”

7. RATIONALIZATION OF PRESCRIPTION PRACTISES
Introduction of Essential drug list limits the use of non-essential drugs.
Provided details of pharmacokinetics help the physician in selecting right kind of drug and dosage form.

8. RATIONALIZATION OF PRESCRIPTION PRACTISES
Prescription of Rational drugs requires:
Accurate diagnosis.
Selection of best drug from the available.
Prescribing adequate drug for a sufficient length of time.
Choosing the most suitable drug, weighing of effectiveness, safety, and availability and cost.

9. RATIONALIZATION OF PRESCRIPTION PRACTISES
Most of the illness respond to simple, inexpensive drugs,
Physician should avoid :
Use of expensive drugs.
Use of drugs in nonspecific conditions (e.g., use of vitamins).
Use of not required forms (e.g. injection in place of capsules, syrup in place of tablets)

10. RATIONALIZATION OF PRESCRIPTION PRACTISES
Most of the illness respond to simple, inexpensive drugs, even of improve with no therapy at all.
Physician should avoid :
Multiple drug prescription (bullet treatment) even if it is considered in the best of the patient in a given situation.

11. Characteristics of good and bad prescribing
Good prescribing
Bad prescribing
Effective
Ineffective
Safe
Unsafe
Patient centred and individualized
Not patient centred
Acceptable to patient
Not suitable for patient
Appropriate (not too little or too much)
Inappropriate
Addresses expectations of patient
Causes patient distress and harm
Judicious use of resources
Higher cost
Well informed (evidence based)
Poorly informed
Based on unbiased information
Based on biased information
Low vulnerability to outside influences
Vulnerable to outside influence

12. World Health Organisation Guide to Good Prescribing Steps:
Make diagnosis
Set therapeutic goal for the individual patient
Decide on the therapeutic approach
Choose a drug class
Choose a generic drug within a class

13. World Health Organisation Guide to Good Prescribing Steps:
Individualize dose, formulation, frequency, and duration
Verify suitability of chosen drug
Write prescription
Inform patient
Monitor for effects and adverse effects
Alter prescription, if necessary

14. Selecting a P-drug Step i : Define the diagnosis
Step ii : Specify the therapeutic objective
Step iii : Make an inventory of effective groups of drugs
Step iv : Choose an effective group according to criteria (evidence based)
Step v : Choose a P-drug

15. Case Study
Abdullah is 67 years old and has had three documented blood pressures over 150/90 as well as 24 hour ambulatory blood pressure monitoring showing a mean daytime BP of 162/82. He is slightly overweight (BMI 28), and an ex-smoker.
He has some arthritis in his knees that he takes Celebrex® (celecoxib) for. He also has diet controlled diabetes, with no evidence of diabetic complications.

16. 1. Define Diagnosis
Hypertension

17. 2. Specify therapeutic objectives
Therapeutic goal is the answer to the patient’s
question: ‘Why am I taking this medication’?
*prevent cardiovascular events rather than
just reducing the blood pressure per se.

18. Decide on therapeutic approach
Using pharmacological as well as nondrug therapy
Consideration should be given to ceasing the Celebrex as this can aggravate hypertension.
Assessing and addressing his lipids, dietary advice, or consideration of aspirin as primary prevention.

19. The Concept of p-drug list
There is a need for evidence based, rational prescription
Each GP has his/her own context with different needs and priorities
Scientists at the University of Groningen suggested a method where each doctor prepares a list of essential drugs for different conditions
P-drug concept has been propagated by the WHO Action Program on Essential Drugs world wide
Kawakami J, Mimura Y, Adachi I, Takeguchi N. [Application of personal drug (P-drug) seminar to clinical pharmacy education in the graduate school of pharmaceutical sciences]. Yakugaku Zasshi Oct;122(10):819-29

20. Make an inventory of effective groups of drugs
The choice is based on their comparative
efficacy, safety, cost and suitability .

21. Antihypertensive Drugs
thiazides, beta-blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin II receptor blockers (ARB).

22. Find evidences
Wright JM, Musini VM, First line drugs for hypertension. Cochrane Database Syst Rev 2009 Jul 8; (3)

23. First line drug for hypertension
PRIMARY OBJECTIVE:
To quantify the benefits and harms of the major first-line anti-hypertensive drug classes: thiazides, beta-blockers, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, alpha-blockers, and angiotensin II receptor blockers (ARB).
SELECTION CRITERIA:
Randomized trials of at least one year duration comparing one of 6 major drug classes with a placebo or no treatment. More than 70% of people must have BP >140/90 mmHg at baseline.

24. First line drug for hypertension
DATA COLLECTION AND ANALYSIS:
The outcomes assessed were
mortality, stroke, coronary heart disease (CHD), cardiovascular events (CVS),
decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects.
Risk ratio (RR) and a fixed effects model were used to combine outcomes across trials.

25. Thiazide for total mortality

26. Thiazide for total stroke

27. Thiazide for total stroke (high dose)

28. TOTAL CHD

29. TOTAL CV EVENTS

30. Beta Blocker & ACE-Inhibitors
Beta blockers (five RCTs)
reduced stroke (RR = 0.83; 95% CI, 0.72 to 0.97)
cardiovascular events (RR = 0.89; 95% CI, 0.81 to 0.98),
but not CHD (RR = 0.90; 95% CI, 0.78 to 1.03) or mortality (RR = 0.96; 95% CI, 0.86 to 1.07).
ACE inhibitors (three RCTs)
reduced mortality (RR = 0.83; 95% CI, 0.72 to 0.95),
stroke (RR = 0.65; 95% CI, 0.52 to 0.82),
CHD (RR = 0.81; 95% CI, 0.70 to 0.94), and
cardiovascular events (RR = 0.76; 95% CI, 0.67 to 0.85).

31. Ca Channel Blockers Calcium channel blockers (one RCT)
reduced stroke (RR = 0.58; 95% CI, 0.41 to 0.84) and
cardiovascular events (RR = 0.71; 95% CI, 0.57 to 0.87),
but not CHD (RR = 0.77; 95% CI, 0.55 to 1.09) or mortality (RR = 0.86; 95% CI, 0.68 to 1.09).

32. Efficacy
There is evidence from the HOPE study that diabetic patients may get a mortality benefit from angiotensin converting enzyme (ACE) inhibitors independent of their effect on blood pressure.
Angiotensin converting enzyme inhibitors would also be effective in preventing diabetic renal complications, so in terms of efficacy, ACE inhibitors would be our first choice, followed by thiazides.

33. The process of rational treatment
Step 1: Define the patient’s problem
Step 2: Specify the therapeutic objective
Step 3: Verify the suitability of your P-treatment
Step 4: Start the treatment
Step 5: Give information, instructions and warnings
Step 6: Monitor (and stop?) treatment

34. Safety
consider the frequency as well as the severity of adverse reactions
special groups who may be particularly at risk of adverse reactions. E.g. gout with thiazides

35. NNT & NNH

36. Costs Cost to the patient Cost to the community for subsided drugs
Costs associated with monitoring, treatment failure and side effects

37. Suitability (Convenience)
Frequency/monitoring/formulation
Verify suitability the chosen drugs

38. Choose generic drugs within a class
chose to prescribe atenolol instead of metoprolol because it is less lipophilic and less likely to result in central nervous system adverse reactions, as well as being a once daily medication.
Among the ACE inhibitors the only difference is that captopril requires more frequent daily dosing.

39. Individualize dose, formulation, frequency and duration
a low dose of ACE inhibitor should be chosen and titrated up slowly because he is already taking celecoxib

40. Nomenclatur EU and US Innovator’s drug product Generic drug
The reference formulation
Generic drug
Supposedly bioequivalent and interchangeable with the innovator’s drug
Similar or copy drug
Same active ingredient as the reference product
Branded drug
Generic, similars and copies can be branded

41. Substandard and Counterfeit Drugs Defined by WHO
Substandard drug
A “genuine” drug product
Does not meet quality specifications
Spurious /falsely-labelled /falsified /counterfeit (SFFC) medicines
Deliberately and fraudulently mislabeled with respect to identity and/or source.
Both branded and generic products
May include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient or too much active ingredient, or with fake packaging

42. Making Counterfeit Drugs is a Criminal Offence

43. Substandard Drugs

44. Counterfeit & Substandard Drugs
10-15% of the total drugs market
Some areas in Asia and Africa reaching levels of almost 50%
Substandard
Difficult to say
Can be as high as 40% of the total sample size
Roger Cockburn et al, „The Global Threat of Counterfeit Drugs: Why Industry and Governments Must Communicate the Dangers‟, PLoS Medicine, 2(4), March 2005,
O. Shakoor, et al, „Assessment of the Incidence…‟, Tropical Medicine and International Health, p

45. Substandard/falsified drugs

46. Streptokinase Activity
Hermentin et al, European Heart Journal (2005) 26, 933–940

47. The Generic Approval Process
Abbreviated New Drug Application (ANDA)
Same dosage form
Same route of administration
Same amount of active ingredient(s)
Follow Good Manufacturing Practice (GMP) Guidelines
Bioequivalence

48. Bioequivalence Simple crossover study
Small number of healthy volunteers
Compares
Pharmacokinetic data (drug concentrations)
Not Clinical data
Essentially, a simple in vivo test of quality
Usually done in a Contract Research Organization NOT a hospital

49. False data /data manipulation

50. Generic Docetaxel Tested
31 formulations tested
Only 10 within acceptable range 90–110%
Others
21 < 90%
11 < 80%
1 < 40%
Current Medical Research and Opinion 24(7), 2019 – 2033, 2008

51. Impurities
Even small amounts of impurities can affect the efficacy and safety of a product
Limits for impurities, including degradation products, have been established by the ICH
Formulation should adheres strictly to the lower limits for impurities
Roy. AAPS PharmSciTech. 2002;3:E6; ICH Harmonised Tripartite Guideline.. Impurities in New Drug Products. International Conference on Harmonization; 2006

52. Docetaxel Impurities
Docetaxel impurtiies

53. Generic Docetaxol - Total Impurity Content
Acceptable impurity level (3%) was defined as twice the amount in the reference product

54. Generic Docetaxol – Drug Content
Error bars indicate the variability between the two vials analysed
Adapted/Reproduced from Vial J, et al. Curr Med Res Opin 2008;24:2019–33

55. Tragic Indian

56. Tragic Indian Antibiotic pills contaminated with rat poison?
Police raids of Mahawar Pharma
Small company supplying medicines to the state government
Antibiotic ciprofloxacin
Contained zinc phosphide
Highly potent rodenticide

57. GMP Storage & processing

58. Write correct prescription
writing the prescription is only a small part of the whole prescribing process.
document the prescription in the case notes with the date, dose and indication to allow ease of review

59. Provide information to the patient
Discussion of the therapeutic goal / therapeutic approach/adverse reactions (eg. cough with ACE inhibitors) /rare serious reactions (eg. angioedema with ACE inhibitors).
written information

60. Monitor for effects and adverse effects
In the case of Abdullah, he should be brought back for monitoring of his blood pressure, as well as renal function 1–2 weeks after commencement of the prescribed drug

61. If necessary, alter prescription The response may be:
alter the dose,
cease the medication
prescribe another agent or try alternative non-pharmacological approaches.

62. Using a P-drug list
You then add the ACE inhibitor that you have chosen to your P-drug list, and you prescribe it for all of your diabetic hypertensive's from then on, unless there is a particular suitability issue.
The choice takes a bit longer the first time, but it is then rational, appropriate and evidence based

63. Using a P-drug list
it also has the benefit of saving time on future consultations because you know exactly what to prescribe.
Also, when a new drug is being marketed for the treatment of hypertension, in order for it to become your first line treatment on your P-drug list, you have to see proof that it is better than the ACE inhibitor for diabetic patients.

64. Conclusion
Prescribing is an important behavior that GPs regularly practice.
The WHO has developed a structured guide to good prescribing and the steps in this process are easy to learn and apply in day to day practice

65. Central to this process is the development of a personal formulary (P-drug list) where a limited number of drugs are chosen for specific indications with choices being made on rational and evidence based grounds.
By prescribing according to a well founded P-drug list, GPs can develop greater familiarity and confidence in the prescribing with
improved outcomes for patients.

66. Terima kasih