Rational prescribing,dispensing and use of drugs

This presentation contains explanation of Rational prescribing,dispensing and use of drugs.

1. Clinical Pharmacy Final Professional 1

2. Rational use of drugs Rational Prescribing Rational Dispensing Problems of Irrational Drug Use Learning about drug use problem Sampling to study drug use Indicators of drug use 2

3. Basic Pharmacology Principal mechanisms of pharmaceutical action, metabolism, absorption, distribution, and elimination. Knowledge about interactions between medicines and living systems at theoretical level. Clinical Pharmacology Study medicine with regard to clinical efficacy, risks, clinical pharmacokinetics, drug-drug interactions, drug disease interactions, drug genetic interactions, the concepts of clinical trials, and pharmacoeconomics . How to use medicines properly and rationally at more practical level. Therapeutics The use of pharmaceuticals to treat disease. Practical application of basic and clinical pharmacology . 3

4. Rational Use of Drugs Rational means “based on or in accordance with reason or logic” “Rational use of drug means the right drug for the right patient, in the right dose, at right time, by the right route and should be economical.” WHO Definition “Patient receiving medication appropriate to their clinical needs, in appropriate doses, for an adequate period of time and at the lowest cost to them and their community” Also Defined as, “ The safe, effective, appropriate and economic use of drugs.” 4

5. Explanation Safety : All drug posses side effects, less or more. The safety aspects of drug can be assessed from different angles such as; Severity of the disease Available treatment options Long term and short term treatment Effectiveness : How the drug works in daily practice. Efficacy: When drug used in particular disease in particular number patients and it shows its maximum therapeutic effects. 5

6. Appropriateness : How the drug is being prescribed and used by the patient? Appropriate indications Appropriate dosage and administration Appropriate dispensing and duration of treatment Appropriate patient counseling Economical : Does not, only relates to “price”. Cost effectiveness approach should be adopted 6

7. Approaches to achieve Rational use of drugs 1. Patient Problem Understand the causes of the problem of patient Detail history of the illness Medication history of patient 2. Diagnosis Past medical history Including medication history (OTC/ Prescription medicine) Present complaints (lab findings) If patient is not diagnosed accurately then the therapy is termed as irrational therapy or treatment . Accurate diagnosis is a prerequisite for rational therapy. 7

8. 3. Therapeutic objectives Relieving symptoms Preventing disease Combination of both 4. Treatment option Treatment options (Drug of choice or changes in life style) If drug is required, then selection is based on; Efficacy Safety Suitability Cost Effective Ease of administration Storage requirements 8

9. 5. Start treatment Drug should be prescribed & start drug administration Educate the patient about the beneficial and side effects of drug How the patient should deal with side effects Next visit should be planed for patient to assess the treatment 6. Result of the treatment Result is obtained from physical examination and from the lab investigations. If the patient responds to therapy, it is termed as rational therapy and if vice versa then assess the problem from step 1. 9

10. 7. Conclusion of therapy Judge from the results; 1) Therapeutic goals achieved? 2) Patient problems solved? If these questions are not answered then 1)Verify whether the patient showed compliance or not? 2) Do all the diagnosis again 10

11. Rational use of drug can be achieved by drug use process (DUP) indicators 11

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13. Core interventions to promote more rational use of medicines 1. A mandated multi-disciplinary national body to coordinate medicine use policies 2. Clinical guidelines 3. Essential medicines list based on treatments of choice 4. Drugs and therapeutics committees in districts and hospitals 5. Problem-based pharmacotherapy training in undergraduate curricula 6. Continuing in-service medical education as a licensure requirement 13

14. 7. Supervision, audit and feedback 8. Independent information on medicines 9. Public education about medicines 10. Avoidance of perverse financial incentives 11. Appropriate and enforced regulation 12. Sufficient government expenditure to ensure availability of medicines and staff 14

15. Rational Prescribing There is no universally agreed definition of good prescribing. The WHO promotes the rational use of medicines, which requires “ 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 cost to them and their community” . The prescriber should have the following four aims: 1) Maximize effectiveness 2) Minimize risks 3) Minimize costs 4)Respect the patient's choices. 15

16. 16 Basic Professional Behaviors Expected in Practice Professional behavior Ethical principle Do the very best you can for every patient Beneficence In all cases, do no harm Nonmaleficence Tell the patient the truth Veracity Be fair Justice Be loyal Fidelity Allow the patient to be the ultimate decision maker Autonomy/paternalism Always protect your patient's privacy Confidentiality

17. 17 This model links to the four key principles of biomedical ethics: beneficence, non- maleficence , justice and veracity, and respect for autonomy (confidentiality and consent), and can be applied to decision making at both an individual patient level and when making decisions about medicines for a wider population, for example in a Drug and Therapeutics Committee. One of the strengths of this model is the consideration of the patient's perspective and the recognition of the inherent tensions between the four key aims. For further readings: (Clinical Pharmacy and therapeutics by Roger Walker)

18. 18 Another popular framework to support rational prescribing decisions is known as STEPS Safety Tolerability Effectiveness Price Simplicity

19. 19 A framework for good prescribing

20. 20 Criteria for rational prescribing Appropriate diagnosis (Depend upon clinical and lab investigations) 2. Appropriate indication (Drug therapy is safe and effective) 3. Appropriate drug 4. Appropriate patient (hypersensitivity, contraindicated drugs in certain patients) 5. Appropriate dosage (pediatric, geriatric, or having concomitant disease) 6.Appropriate duration 7. Appropriate route of administration 8. Appropriate information 9. Appropriate monitoring (both by patient & prescriber)

21. 21 Rational Dispensing The well controlled preparation and supply of medicine to the ultimate right patient in response of the prescription of the prescriber is called rational dispensing. OR Interpretation and evaluation of a prescription, selection and manipulation or compounding of a pharmaceutical product, labeling and supply of the product in an appropriate container according to legal and regulatory requirements, and the provision of information and instructions by a pharmacist, or under the supervision of a pharmacist, to ensure the safe and effective use by the patient.

22. 22 Requirements/Knowledge for rational dispensing i ). Stability of dispensed medicine and their ingredients ii). Principles of compounding iii) Dosage form and dosage schedule iv) Physical, chemical and therapeutic incompatibilities v) Packaging materials and methods vi) Labeling procedures vii) Legal requirements

23. 23 Dispenser A qualified individual who “prepares” and “gives out” the remedies/medicine according to the physician prescription. The dispenser must have a sound knowledge of Pharmacology, medicinal chemistry, microbiology, pharmatechnology , forensic pharmacy, pharmaceutical calculations etc. He/She must know about the stability of the dispensed medicine and the ingredients, physical, chemical and therapeutic incompatibilities, labeling and packing material etc.

24. 24 Dispensing process/rational dispensing Dispenser assumptions that; 1) The prescriber has made correct diagnosis, selected correct drug, dosage and quantity 2) Patient has access to the dispensary or pharmacy

25. 25 Important steps of rational dispensing Receiving of Prescription The dispenser receives the “correct” prescription from the prescriber directly or through Patient. It can be through Phone, oral/verbal and/or online computer system. Origin of the prescription Validity of the prescription Relevant instructions Information about patient Therapeutic appropriateness Economic considerations Communication with prescriber for unclear instructions

26. 26 2. Interpretation of prescription Name of the drugs Dosage, administration and duration Availability of drugs Retrieves drugs from storage area 3.Checking of the prescription Check the expiry date and storage condition of the prescribed drug. Follow FIFO rule Checks and counter check (identify strength & dosage form)

27. 27 4. Filling of prescription The dispenser should have true knowledge of the medication and its proper use and can: Precisely dispense products Re-check drugs and dosages 5. Labeling of prescription (identification of drugs and instructions) The dispenser communicates in correct way to take the medication to the patient through labels with patient’s name, drug name and directions for use, date of dispensing, identity of dispenser Identity of prescriber symbolic instructions in case of illiterate patients Use of auxiliary labels Name and sign of dispenser

28. 28 6. Handling of prescription The patient understands the instructions from the dispenser. The dispenser will: Repeat orally the labeled instructions Ask the patient to repeat the instruction Emphasizes the need for compliance Providing warnings and cautions Gives special attention to certain cases ( pregnant women, those with visual/hearing problems, children and elderly patients, those taking multiple medications 7. Instruction for patients Comply with the instructions for therapy

29. 29 8. Record Dispenser keeps accurate records of the following operations Enters details of encounter on patient profile card Enters in prescription register Completes inventory records There are many potential areas in which the dispenser can make mistakes. Dispensing requires trained, skilled, responsible individual, proper policies and incentives must be provided to attract such personnel and develop this profession

30. 30 Inappropriate or irrational prescribing Good prescribing is sometimes defined as the lack of irrational prescribing. Prescribing can be described as irrational for many reasons: Poor choice of a medicine Polypharmacy or co-prescribing of interacting medicine Prescribing for a self-limiting condition Continuing to prescribe for a longer period than necessary Prescribing too low a dose of a medicine Prescribing without taking account of the patient's wishes.

31. 31 Consequences of irrational prescribing Inappropriate or irrational prescribing can result in serious morbidity and mortality, particularly when childhood infections or chronic diseases such as hypertension, diabetes, epilepsy and mental disorders are being treated. Inappropriate prescribing also represents a waste of resources and, as in the case of antimicrobials, may harm the health of the public by contributing to increased antimicrobial resistance. Over-willingness to prescribe stimulates inappropriate patient demand and fails to help the patient understand when they should seek out support from a health care professional.

32. 32 Causes of irrational use of drugs Selection of drugs (Drug selection based upon efficacy, safety, cost, & availability) 2. Patient requirement (Dosage form and dose adjustment in different age groups and disease states) 3. Compliance (To improve compliance give the following information to patient: Drug positive aspects, side effects, precautions, warnings) 4. Incorrect prescribing/ Inappropiate prescribing( A wrong drug is prescribed) 5. Polypharmacy 6. Multiple prescription 7. Incorrect administration 8. Expensive drugs

33. 33 Factors responsible for irrational use of drugs Health system i ) Unreliable Drug supply ii) Drug shortages iii)Heavy patient load iv) Lack of staff v) Lack of diagnostic tools/labs vi)Lack of regulation enforcement 2. Prescriber I) Internal factors a) Inadequate training b) Outdated prescribing practices (lack of continuing education) c) Misleading beliefs

34. 34 II) External factors a) Heavy patient load b) Profit may affect prescribers choice 3. Dispenser i ) Inappropriate training ii) Shortage of dispensing material iii) Short dispensing time iv) Low status of dispenser affects the quality of dispensing 4. Patient & community Cultural beliefs Patient and community beliefs about drugs Shortage of printed information

35. 35 5. Industry Promotional activities Misleading claims Pharma industry against generic system

36. 36 Learning about drug use problems Individual drug use problems take place within a system of drug supply and within a network of beliefs on the part of providers and patients . To “change a problem behavior”, we must learn about the behavior itself and about the determinants which underlie it. Objectives of learning about a drug use problem To describe a “model” for developing interventions Identify potential source of “data "for learning about drug use problems and evaluate their relative strengths and weakness 3. Understand the importance of studying “provider” and “patient” motivation 4. Motivations and incentives when developing a program to improve drug use

37. 37 5. Appreciate the role of qualitative research methods for learning about drug use behaviors (by group discussions, interview, survey/form fill) 7. Develop techniques for field visits Changing drug use problems The process of identifying, understanding and changing drug use problems is similar to the process of diagnosis and treating a clinical illness

38. 38 Schematic representation Changing a drug use problem

39. 39 Process explanation Examine Identify a priority drug use issue a) Which potential problems carry the highest clinical risk? b) Which involves expensive/widely used drugs? c) which are potentially the easiest to correct? ii) Collect data to measure current practice a) Which source of data will give you the best source of information? b) How large a sample is necessary to get reliable information? c) What are the groups of interest e.g., Doctors & nurses or public sector and mission facilities

40. 40 2) Diagnose i ) Describe in detail apparent problems in drug use a) What specific practices are the problem? b) What is an ideal practice c) Who are the most important providers e.g., the influence leaders in the community etc d) Are there high risk patient e.g., pregnant women or young children ii) Identifying the apparent causes of the problem a) What social and cultural factors influence practices? b) What do providers know and believe? c) What do patients expect when they visit a providers

41. 41 iii) Identify constraints to change Economic factors prevent change Drug supply factors will hinder change work environment 3) Treat (design & implement interventions) Select “target behavior” to change & design an intervention program Which behavior can be changed most cost effectively? What are the possible economic consequences? What are the most important appropriate interventions, give their different costs, complexities & chances of success? What personnel will be required & what training will they need?

42. 42 ii) Conduct pilot tests to determine the acceptability and effectiveness of an intervention iii) Implement the intervention and collect data to measure changes Is the intervention implemented as expected How are the program impacts to be measured? Is the data reliable ? 4) Follow up Evaluate the interventions success Was the intervention implemented as planned? What are the measureable changes e.g., Patient satisfaction, clinical results etc., How cost effective is the intervention as compared to the other strategies ?

43. 43 ii) Feed back results to program personnel, to providers & to consumer to encourage them to maintain & increase positive changes iii ) Use results to improve the impact of the program or to guide decisions about other problems to investigate

44. 44 Who Is a Prescriber? Or Whose Behavior Do We Change? Physicians Paramedics Pharmacists Injectionists Patients Clinical officers Clinic attendants Dispensers Drug sellers Relatives/friends

45. 45 Sampling to Study Drug Use Sampling is a process by which we study a small part of a population to make judgments about the entire population Sampling involves selecting a number of units from a defined population. Sampling Unit - The thing that is sampled: for example, a person, clinical episode, or health facility Study Population - All the sampling units that could possibly be included in the sample Sampling Frame - A list of all the available sampling units in the study population

46. 46 Representative sample A representative sample has all the important characteristics of the study population from which it is drawn. Sampling Methods Two categories of sampling methods: - Non-probability sampling - Probability sampling Non-probability Sampling Methods Convenience Sampling - Study units available at the time of data collection are selected for the sample ( subjects are selected because of their convenient accessibility and proximity to the researcher) Quota Sampling - Different categories of sample units are included until a certain number has been reached in each category ( For example, a researcher might ask for a sample of 100 females, or 100 individuals between the ages of 20-30)

47. 47 Sample Size The optimal sample size is often a compromise between what is statistically Desirable and what is practically Feasible Types of study i ) Experimental clinical trials ii) Non-experimental observations a) Cohort study ( In a cohort study, an investigator selects a group of non-diseased people and follows them over time to determine if they develop a disease/outcome.  The cohort is selected based on exposure status, including both people who have been exposed and those who have not. The main characteristic in a cohort study is that the study proceeds from cause to effect). b) Case control study ( The case-control is a type of epidemiological observational study. An observational study is a study in which subjects are not randomized to the exposed or unexposed groups, rather the subjects are observed in order to determine both their exposure and their outcome status and the exposure status is thus not determined by the researcher)

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49. 49 Probability Sampling Methods Simple Random Sampling Systematic Sampling Stratified Sampling Cluster Sampling Multistage Sampling Simple Random Sampling Used in situations where the number of sampling units is relatively small Process: - Identify all possible units available for sampling - Decide on the size of the sample - Choose units by a lottery method

50. 50 Systematic Sampling In this case sample units are selected from a numbered list of all units in the study population by using a regular interval starting from a random starting point. To calculate sampling interval divide the size of the list by the desired sample size. Stratified Sampling Used when the sampling frame contains clearly different categories (strata) For example, Urban and rural facilities Facilities with and without doctors Government and mission facilities

51. 51 Process - Organize the list of sampling units by stratum - Select units within each stratum using a random method (simple random sampling or systematic sampling) Cluster Sampling Used when, for logistic reasons, it is easier to select sample units in groups Process - Select a cluster of sample units Example: health center with multiple prescribers Include the entire cluster or select a subsample or Select a random sample unit to start each cluster (a house, a patient, etc.) - Include neighboring sample units until a certain cluster size is reached

52. 52 Multistage Sampling Randomly select primary sampling units at the first stage: Specific communities Specific health facilities Within the primary sampling units, randomly select the final sampling units at the second stage: Drug use encounters Patients Households Sometimes in complex samples, additional stages are needed multistage sample in which 20 health facilities are selected, and then 30 drug use encounters are sampled within each facility.

53. 53 Collecting data to learn about drug use problem Two steps in “learning about drug use problem” are; collecting data of drug use problem finding correct cause of problem Methods of collecting data Quantitative method Qualitative method Quantitative method It is numeric data (counts, rates, or clarifications) Used to identify specific problems or to measure the success of interventions How to collect quantitative data Routinely reported data Data gathered from record systems Sample surveys

54. 54 Types of Quantitative method Retrospectively & prospectively Aggregated data(monthly drug consumption & patient specific record Detailed data (name,doses,amount,duration,cost) non detailed data (name of drug only) Information available in quantitative data Data from drug (use) encounters Facility ID ___________ Characteristics_________ Equipments ____________ Drugs available__________

55. 55 Patient ID_________ Data________ Age_________ Gender ________ Symptoms _________ Attitudes__________ Beliefs ____________ Interaction History __________ Examination ________ Diagnosis _________ Time spent_________ Explanation about drugs _______ Explanation about illness________

56. 56 Drugs Name _______ Brand/generic______ Form_______ Quantity _______ Duration _________ If dispensed______ How labeled______ Cost _______ Patient charge _________ Qualitative method Quantity data quantify the problems but do not answer that why the problem exists. Types of qualitative data i ) In depth discussions ii) focus group discussion iii)Structural observations iv) structured questionnaires v) structured patient visits

57. 57 Drug use indicators Indicators are specific objective measures that allow the evaluation of the baseline situation and progress in systems and the assessment of services and interventions Purpose of Drug use indicators Objective measures (Indicators) that can describe the drug use situation in a country/region/Health facility. These indicators will allow Health planners, Managers and Researchers, to make basic comparisons between situations in different areas or at different times. The indicators can be used to measure the impact of the interventions undertaken.

58. 58 The indicators can serve as simple supervisory tools to detect problems in performance of individual providers or Health facilities. The drug use indicators can be used as "first line measures " to stimulate further questioning and to guide subsequent action. Performing an indicator study is useful method to— •Identify medicine use problems at the individual patient level •Monitor medicine use by prescribers •Evaluate the impact of interventions Type of Indicators: Indicators are developed to be used in measures of performance in three general areas, related to the Rational use of Drugs in Primary care. * Prescribing practices by Health providers * Patient care including both clinical consultation and pharmaceutical dispensing. * Facility specific factors which support RUD.

59. 59 Core Indicators Core indicators are those considered to be highly relevant, important and useful The core prescribing indicators measure general prescribing tendencies within a given setting, independent of specific diagnoses. Many critical questions in drug use have to do with whether health care providers follow appropriate diagnostic procedures and whether they select products and dosage schedules to fit underlying health problems. However, determining the quality of diagnosis and evaluating the adequacy of drug choices is a complex undertaking in practice, and beyond the scope of the core indicators.

60. 60 After a first drug use study with selected indicators has been carried out to determine overall prescribing performance, it will usually be necessary to undertake more health problem-specific investigations and make an assessment of the quality of diagnosis and treatment

61. 61 Facility Indicators * Availability of essential drug list or formulary * Availability of key drugs. Availability of standard treatment guideline (STG) These indicators are of activity based measures, meant to describe practices in a representative sample of Health facilities. The drug use indicators can be collected at one time in a cross sectional survey, or otherwise. For a basic cross sectional survey about 20 health facilities can be selected to represent a larger group of facilities.

62. 62 Care Drug use Indicators I. Prescribing indicators * Average number of drugs per encounter * Percentage of drugs prescribed by generic name * Percentage of Encounters with an antibiotic prescribed * Percentage of encounters with an injection prescribed Percentage of drugs prescribed from essential drug list or formulary. II. Patient care Indicators * Average consultation time * Average dispensing time * Percentage of drugs actually dispensed * Percentage of drugs adequately labeled * Patients knowledge of correct dosage

63. 63 The prescribing indicators can be based on either Retrospective or prospective data. Retrospective data describe the drug use during patient list that took place in the past. These data can be collected from medical records kept in the Health facilities. Prospective data describes the drug use during patient visits that takes place on the day of the indicator survey.

64. 64 Complementary drug use indicators Complementary indicators are those additional measurements considered to be relevant and useful. These indicators represent measures of performance that can be used in addition to the core indicators are no less important than the core indicators, but the data to measure them may often be more difficult to obtain, or their interpretation may be highly sensitive to the local context. The required data can be collected in a drug use survey with core indications. The complementary indication are suggested as additional measures of drug use.

65. 65 Complementary drug use indicators can be * Percentage of patients treated without drugs * Average drug cost per encounter. * Percentage of drug costs spent on Antibiotics * Percentage of drug costs spent on Injections * Prescriptions in accordance with treatment guidelines * Percentage of patients satisfied with the care they received * Percentage of health facilities with access to impartial drug information.

66. 66 Performing an Indicator Study Determine objectives, priorities, and indicators •Determine study design according to objectives •Monitoring over time, comparing facilities •Cross-sectional survey, time series •Evaluating interventions •Randomized controlled trial, pre/post with control, time series •Define indicators and data collection procedures •Pilot-test procedures

67. 67 Train data collectors •Randomly select facilities (at least 20 if possible) in the region from which to collect data •Obtain approximately 30 medicine use encounters for each facility (100 if only one facility is chosen) •Analyze data •Provide results to DTC for evaluation and follow-up

68. 68 Results can be used as follows— •Describing current treatment practices •Comparing the performance of individual facilities or practitioners •Periodic monitoring and supervision of specific medicine use behaviors •Identifying potential medicine problems that affect patient care •Assessing the impact of an intervention

69. 69 Hospital Antimicrobial Indicators Introduction/Background (1) • These indicators and manual is intended as a rapid assessment tool to identify problems with antimicrobial use in their hospitals. •Designed to evaluate and improve antimicrobial use. •Indicators will allow basic comparisons of antimicrobial use both in one hospital over time and between hospitals.

70. 70 Hospital Antimicrobial Indicators Introduction/Background (2) •Indicators can be used at the district, regional, or referral hospital level. • Tool can be used by • hospital administrators, • drug and therapeutics committees (DTCs), • researchers and program managers

71. 71 Hospital Indicators •Existence of STG for infectious diseases •Existence of an approved hospital formulary list or Essential medicine list •Availability of a key set of antimicrobials in the hospital stored on the day of the study •Average number of days that this key set of antimicrobials are out of stock over 12 months •Expenditure on antimicrobial medicines as a percentage of total hospital medicine costs

72. 72 Prescribing indicators (eight indicators) •Percent of hospitalizations with one or more antimicrobials prescribed •Average number of antimicrobial medicines prescribed per hospitalization •Percent of antimicrobials prescribed consistent with formulary list •Average cost of antimicrobials prescribed from hospitalizations with one or more antimicrobial prescribed •Average number of doses of surgical antimicrobial prophylaxis for Cesarean Section procedures •Percent of pneumonia patients who are prescribed antimicrobials in accordance with STG •Percent of antimicrobials prescribed by generic name

73. 73 •Average duration of prescribed antimicrobial treatment •Percent of patients that have a Cesarean Section procedure that receive Surgical Antibiotic Prophylaxis according to hospital guidelines (or international guidelines)

74. 74 Patient care indicators •% of doses of prescribed antimicrobial medicines actually administered •Average duration of stay of patients who receive antimicrobials •Supplemental indicator •Number of antimicrobial medicine sensitivity tests reported

75. 75 Results of Indicator Studies •Conducting a indicator study will allow comparisons of antimicrobial use both in one hospital over time and between hospitals •General and specific problems with antibiotic use can be identified using these indicators •After problems have been detected, investigators will need to interpret the meaning of the results in the context of the hospital (size, type of patient, level of complexity) and probe more deeply to uncover possible underlying causes

76. 76 Medical error Case Study Objectives  Learn step-by-step what to do when medical error occurs and how to report it.  Learn how to identify root cause of a medical error and how to prevent its recurrence.  Motivate your colleagues to foster a patient safety culture

77. 77 The Story occurred On Sunday morning, Mr. Xy had attended my clinic due to marked polyuria . His RBS was 28.8 mmol /L, otherwise he was completely normal. I’ve prescribed N. saline 1.5 L , IV, over 2 hours and 5.0 u of regular insulin by direct IV push / 30 minutes, until his RBS is 9.0 mmol /l. I’ve been called to give the IV injection, Which was easily done. Twenty minutes later, my patient was very much apprehensive, sweating and started shivering. His RBS was 0.8 mmol /l. The Story My nurse had told me that I’ve pushed 50.0 u of regular insulin in the IV line.

78. 78 CASE A A 74 year old man brought to the cardiology department was admitted few days by the renal unit on account generalized weakness of excessive sweating and vomiting of 2 days duration. He developed excessive sweating in the evening. The sweating which was sudden on onset was not associated with exertion. There was associated breath difficulty and dizziness. There were episode of loss of consciousness but no history of abdominal pain. Physical Examination Gen Weak, appearing elderly man, afebrile , acyanosed but sweaty. Vital signs T 36.5 R.R 34/min P.R 74/min B.P 124/85mmHg ABD soft and non-tender, active bowel sounds Hs S4, S1, S2 I/O 1450ml (oral), 1900ml (urine) Chest clear

79. 79 Laboratory Result Na+ 139mEq/L (135-152) K+ 2.7mEq/L (3.7-5.1) Cl 105mEq/L (95-105) HCO3 18mM/L (12) Uric acid 7.5mg/dl (3.0-7.0) BUN 15mg/dl (8.25) CR 125ml/min (125) Assessment-IHD with background pre- hypertension Medication History Tab. Ramipril 5mg daily Tab. Metoprolol 50mg b.d “ Lasix 20mg b.d “ Augmentin 625mg b.d “ A S A 75mg daily “ Metronidazole 400mg tds “ Isosorbid dinitrate 5mg b.d SC Heparin 5000 I.V/ 12hrly

80. 80 CASE B A 77year old female diabetic patient was admitted on account of chest tightness, insomnia and headache for 3days.There was associated chest pain aggravated by activities but revealed at rest. No history of vomiting or loss of consciousness. There was easy fatigability and not a known hypertensive patient. Physical Examination Gen Well-nourished old woman in distress Vital signs PR 70/min regular thickened arterial wall B.P 148/78mmHg ABD within normal limits CNS Grossly intact Hs S1,S2 no murmur clear

81. 81 Result Na 140mEq/L (135-145) K 51mEq/L (40-90) Cl 105mEq/L (100-106) Glu 150mg/dl (70-110) HCO3 27mmol/L (24-30) Ca 8.8mg/dl (9-11) Assessment-IHD with background of HBP (systolic) and diabetes mellitus Medication History I.V Augmentin 1.2g stat: 600mg 8hourly Tab. Daonil 5mg daily Tab. Isosorbide dinitrate 5mg daily Tab. Metformin 50mg b.d Tab. A S A 150mg daily Tab. Lisinopril 2.5mg daily Tab. Lipitor 10mg daily Tab. Lasix 40mg daily Tab. Metoprololtartarate 50mg daily Tab. Aldactone 25mg daily

82. 82 CASE C A 40 year old woman was presented with 3 weeks history of chest pain and dyspnoea at the medical outpatient clinic. She also had a sudden retrosternal pain which radiated to all part of her body with associated weakness and breathlessness but no loss of consciousness and no seizure. There was associated palpitation and progressive dyspnoea on exertion and associated polyuria nocturea and polydypsia but no cough and leg swelling . No family history of hypertension and diabetes. Physical examination Gen Young woman not in distress. Vital signs B.P 140/90mmHg Chest Bilateral rales and pleural rib ABD Benign HS S1,S2 No murmur. Obese with striae P.R 80/min, good vol. Reg.

83. 83 Laboratory Results Na 136mEq/L (135-145) K 40mEq/L (40-90) HCO3 26mM/L (24-30) GLU 81 mg/dl (70-110) Cl 98 mEq /L (100-106) Ca 10mg/dl (9-11) Phos 4mg/dl (3-3.5) Chol 140mg/dl (120-220) Assessment No peripheral edema. Patient with IHD with obesity as a risk factor; hypertension, impaired glucose tolerance. Medication History Tab. Propranolol 20mg b.d Tab. Aspirin 150mg daily ” Paracetamol 1000mg daily ” Glyceryltrinitrate 0.5mg PRN ” Librium 10mg daily ” Ternormin 50mg daily Diazepam 5mg nocte

84. 84 CASE D A 45 year old man was presented with 5 year history recurrent retrosternal discomfort, peppery sensation associated with late meal at the medical out-patient clinic. Pain not associated with exertion. No history of hematemesis . The peppery sensation usually radiate to the upper limbs but not to the neck. No epigastric pain. No associated nausea, vomiting, paroxysmaldyspnoea or orthopnoea . No abdominal discomfort. Pain not reveal by change in position. He takes wine but not cigarette. No family history of hypertension and diabetes Physical Examination Gen Restless, not sweaty. Afebrile , acyanosed , not pale, anoteric . No peripheral lymphadenopathy Vital signs Na 140mEq/L (135-145) K 50mEq/L (40-90) Ca 11mg/dl (9-11) Cl 105mEq/L (100-106) Total cholesterol 190mg/dl (120-220)

85. 85 Laboratory Results P.R 110/min, regular normal B.P 160/110mmHg ABD Soft without masses CNS Conscious and alert, well oriented, cranial nerves grossly intact H.S H.S S4, S1 and S2 Fundoscopy , Normal muscle tone Assessment IHD associated with HBP (Hypertension) Medication history Tab.Isorsorbide dinitrate 5mg b.d Tab Propranolol 40mg b.d ” ASA 300mg O.D ” Ranitidine 150mg b.d ” Diazepam 5mg nocte Susp MMT 300ml qds ” Metchlorpramide 5mg b.d

86. 86 If angina occurs more frequently than two or three times per week, chronic prophylactic therapy is necessary. The three drug classes that can be used for this purpose are Nitrates, B-blockers and Calcium Channel Blockers. Effectiveness of nitrate products can be assessed by decreased use of sublingual nitroglycerin for acute attack of angina, improvement in patient’s quality of life, that is, ability to perform normal activities without experiencing angina and objective assessment by exercise testing. In the four (4) cases studied, nitrate products used were Isosorbid dinitrate 5mg two times daily in patient A, B and D (Table 1,2,4), while Glyceryltrinitrate 0.5mg PRN was used in patient C (Table 3).

87. 87 A decreased pharmacologic response in the presence of continuously or frequently administered nitrate is well documented and is termed nitrate tolerance. Clinically, preventing nitrate tolerance involves the provision of a daily nitrate free interval (nitrate free period). The time of day for providing of a nitrate free interval is usually at night. Problem with nitrate free period has therefore necessitated additional use of ß-Blockers. ß-Blockers are effective anti-ischemic and anti-angina agents that act to decrease myocardial oxygen demand by decreasing heart rate and contractility. It is recommended that all patients with unstable angina receive ß-Blocker therapy unless there are contraindications.

88. 88 In contract, ß-Blockers reduce myocardial contractility and arterial blood pressure and thereby reduce myocardial oxygen demand. A potential problem with ß-Blockers is that they may cause coronary vasoconstriction. With blockade of B2 receptors which mediate vasodilatation, there is unopposed ∂-receptor mediated coronary vasoconstriction. This is a particular concern in patients with rest or variant angina where ß-Blockers could potentially precipitate an angina episode. This may necessitate the combination of Calcium Channel blockers with ß-Blockers.

89. 89 In the four (4) cases studied, ß-Blockers were rationally used as they were used to offset the problem associated with nitrates free period. ß-Blockers have several beneficial effects in Ischemic heart disease. ß-Blockers reduce heart rate mainly during time of sympathetic stimulation which results in reduced cardiac work and thus reduced myocardial oxygen demand. In addition to slowing heart rate, ß-Blockers increase diastolic filling time resulting in increased coronary perfusion and improved oxygen supply. In patient A and B, metoprolol 50mg b.d was used while in patient C & D Propranolol 20mg b.d and 40 mg b.d were used respectively. In patient D, Propranolol was changed to Atenolol the newer generation ß-Blocker to offset the side effect of gastric disturbance of Propranolol .

90. 90 In this study, there was no use of Calcium channel blockers as none of the four patients studied was contraindicated to Beta-Blockers. In addition Calcium channel blockers may also cause gastrointestinal effect such as nausea and constipation thus could not have been used in patient D where the patient was established to have gastrointestinal disturbance. Aspirin as a prophylaxis of infarction at 75 mg to 300 mg daily have proved to be beneficial in all forms of IHD as administered in cases A,B,C and D. In case A, 75mg Aspirin was given daily. In cases B & C it was 150 mg daily and in case D, 300 mg Aspirin was given every other day. This is equivalent to 150 mg daily. Patient suspected of having unstable angina or acute myocardial infarction should immediately be given aspirin 150mg to 300mg to chew or swallow except in case of a definite contraindication such as documented hypersensitivity or acute bleeding. Early administration of aspirin has been shown to be superior to placebo in preventing progression of unstable angina to acute myocardial infarction. Dosage of 75-150mg/day seems to have efficacy similar to 300mg/day. Therefore it is recommended that patients with unstable angina take aspirin 75-300mg daily, the dosage based on clinician or patient preference..

91. 91 Heparin confers additional pharmacotherapeutic benefit in unstable angina and thus additional pharmacotherapeutic benefit is established in the rational use of Heparin 5,000 units every 12 hours in case A. The primary goal of anticoagulant such as Heparin is to prevent extension of the thrombus and thus prevent acute myocardial infarction. Although aspirin is superior to placebo in these patients, data suggest that unfractionated heparin alone may be superior to aspirin alone; interestingly some studies have not shown unfractionated heparin to be superior to aspirin or placebo. Nonetheless the expert panel that develops the clinical practice guideline recommended that unfractionated heparin should be administered immediately when the diagnosis of intermediate to high risk of unstable angina is made. In most patients, unfractionated heparin is given along with aspirin.

92. 92 In institutions not equipped to administer unfractionated heparin by continuous infusion, the recommended regimen is 5000U by intravenous bolus every 4 hours for 2 or 5 days. In patient-A, 5000U heparin was administered every 12 hours along with aspirin. This was rational administration of heparin since it was given along with aspirin. Risk factors reduction should focus on hypertension management and its risk factors such as diabetes management, smoking cessation, lipid lowering therapy, antiplatelet therapy and cardiac rehabilitation therapy exercise. Lipid lowering drug therapy in patients with angina or prior myocardial infarction with average or elevated serum cholesterol concentrations has been shown to reduce cardiovascular morbidity and mortality. Lipitor [ atorvastastatin ] 10mg daily was given to patient B as lipid lowering agent [or lipid lowering drug]. rational as obesity and diabetes are coronary risk factor and this patient is also diabetic. Diabetes and obesity as coronary risk factors may increase cardiovascular morbidity and mortality.

93. 93 Lipitor was rationally given to reduce cardiovascular morbidity and mortality which may result from ischemic heart disease. Captopril Prevention Project (CAPP) trial found Captopril to be equal to diuretics and ß -blockers in preventing cardiovascular morbidity and mortality. ACEI are also additive with B-blockers. In patient A, Ramipril 5mg daily was used in combination with Lasix [ frusemide ] 20mg daily, a loop diuretic and in patient B, with spironolactone 25mg b.d which is a risk factor of ischemic heart disease. In patient C & D, there was no additional antihypertensive used apart from Propranolol , which was changed to Atenolol , a ß blocker. The use of ß –blockers in these patients serves both as antihypertensive and ant ischemic .

94. 94 Metochlorpropamide , a derivative of chlorpropamide , a first generation sulphonylurea is associated with the highest incidence of adverse effects and drug interactions. Metochlorpropamide was used in patient D and there was no drug prescribed that interacted with it. Glibenclamide , a second generation sulphonylurea is a more potent antidiabetic agent. It tends to have fewer drug interactions because they bind nonionically and are present in much lower concentrations than the first generation agents such as Metochlorpropamide . In combination with Metformin , it is an additive therapy to lower hyperglycemia and to prevent the risk factors with diabetes in patient with ischemic heart disease. Augmentin was rationally used in patient A & B as antibiotics and in patient A in combination with Metronidazole . There is no drug interaction reported with any of these drugs in these patients.

95. 95 For patient D, Ranitidine 150mg b.d for peptic ulcer was prescribed. Ranitidine minimally inhibits hepatic metabolism of drugs including Propranolol and Diazepam and it has fewer clinically significant drug interactions. There was a beneficial drug interaction in Patient D where Ranitidine was used only to increase the bioavailability of Propranolol or Atenolol and Diazepam. Treatment of co-morbidities and risk factors such as hypertension, diabetes mellitus, obesity and ulcer should always be taken into consideration before anti-ischemic can be rationally prescribed.