Introduction To The Clinical Pharmacy By Amgad A. Ragab, Pharm D, CCP New York University Medical College New York University Cancer Center New York USA

Human Body $ 44,701,295 VS $ 17.00 1000 gm of Bone Marrow ($23,ooo/gm) Total: $ 23,000,000 7.5 gm of DNA ($1.300,000/gm) Total: $9.700,000 109.2 gm of Immune globulin IgG ($67,000/gm) Total: $ 7,316,400 210 units of erythropoietin hormone ($5/u) Total : $ 1050.00

Human Body Organs The Heart : $ 57,000 The Liver : $ 54,110 The Lung : $ 58,200 X 2 = $ 116,400 The Kidney : $ 45,700 X 2 = $ 194,000 The Pancrease : $ 43,900 The Cornea : $ 4,000 X 2 = $ 8,000 The Egg = $ 7,000 each The Sperm = $ 75.00 each ejaculation

Human Chemistry Iron $ 0.30 Potassium $ 5.95 Carbon $ 1.98 Calcium $ 0.18 Chloride $ 0.17 Phosphours $ 7.12 Iodide $ 0.01 Sulphur $ 1.60 Zinc $ 0.03 Sodium $ 0.11 TOTAL $ 17.00

CASE STUDY A 52-year-old male was admitted to the hospital with fever and fatigue. Lab tests revealed that he was pancytopenic WBC 1000, ANC 300, HGB 5.7, HCT 17% Platelets 97,000, BUN 63, Creatinine 2.2 PMS: Orthotopic heart transplant 14 months before this event Medications: Cyclosporine 100mg PO BID Azathioprine 150mg PO BID Prednisone 10mg PO QD

CASE MANAGEMENT Pt. was admitted to ICU with precautions related to neutropenia He received a blood transfusion (4 units) for anemia Broad-spectrum AB for neutropenia Fluconazole and Ganciclovir for possible fungal or viral infections BM biopsy for possible CMV infection

MEDICAL PROBLEM DISCOVERY Clinical pharmacist interviewed the pt. It was discovered that pt. was being treated with allopurinol 300mg PO QD for hyperuricemia (disorder associated with cyclosporin therapy) 2 months before the hospitalization Drug-drug interaction between allopurinol and azathioprine causes pancytopenia Naranjo score is 7

MECHANISM OF ACTION Azathioprine is metabolized to 6 mercaptopurine 6-MP and then to inactive products by xanthine oxidase Allopurinol is a xanthine oxidase inhibitor Toxic effects on the bone marrow due to higher plasma concentration of 6-MP Pt. remained in hospital for 31 days till the bone marrow slowly recovered Total cost of this stay was $ 180,995,73

Intervention It is recommended changes in the drug therapy for any of the following reasons: Untreated indication. Drug use without an indication. Improper drug selection. Failure to receive drug Subtherapeutic dosage Overdose Adverse Drug Reaction Drug interaction Inappropriate route Monitoring required

ADVERSE DRUG EVENT (ADE) Definition Any injury that results from the use of a drug

CLASSIFICATIONS OF ADE Adverse Drug Reaction (ADR) Any response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis, or therapy of disease Medication Error Any preventable drug event that may cause or lead to inappropriate medication use or patient harm Therapeutic Failure A suboptimal response to drug therapy

ADE CLASSIFICATIONS (CONT.) Adverse Drug Withdrawal Event (ADWE) A noxious or unintended response that occurs when a drug is discontinued (eg, benzodiazepines withdrawal, rebound hypertension with abrupt discontinuation of clonidine Accidental/Intentional Overdose: A drug event due to a supratherapeutic level of a drug, either accidental (childhood poisoning) or intentional (suicide attempt)

INTERVENTION TO RESOLVE PATIENT’S DRUG THERAPY PROBLEM The dose of azathioprine should be reduced by 25-50% Azathioprine dosing should also be reduced in patients that have a renal insufficiency Azathioprine ½ life elimination: Parent drug: 12 minutes 6-MP: 0.7-3hrs May be taken with food,3 hrs difference at least between azathioprine and allopurinol

CLASSIFICATION OF ADR Type I: Augmented reactions Related to pharmacologic effects eg: hypoglycemic coma from insulin hypoprothrombinemia from warfarin 80-85% of all ADRs, considered predictable Type II: Bizarre reactions Related to hypersensitivity or immune mediated reactions 15-20% of all ADRs, considered unpredictable

ADEs & HEALTH CARE SETTINGS A Community 18% of patients experience an ADE More than 50% of office visits due to ADEs are preventable 1.7-28% of ED visits are related to medication mismanagement (70% are preventable) 5-10% of all hospitals admissions are related to ADEs 1/3 of drug related hospitalizations involve patient noncompliance issues

CONT. B. Hospitals 10-30% of hospitalized patients experience an ADE, 1-3% significant Each ADE costs approximately $5000 30-50% of ADEs in hospitalized patients are preventable

CONT. C. Long-term Care 1.89 ADEs per 100 residents occur More than 50% of ADEs are preventable Polypharmacy: The average number of medications taken by elderly patients 5-8 per day The ADE rate among patients receiving 1-3 drugs: 6% More than 6 drugs the rate is 52%

ADEs STATISTICS Warfarin 95% Antidiabetic agents 94% NSAIDs 89% Digoxin 82% Antiepileptic drugs 69% Inadequate monitoring of drug therapy 67% Inappropriate dose 51% Patient compliance 33% Drug-drug interaction 26% Contraindication 3% Allergy 1%

CONCLUSION THE ANNUAL COST OF DRUG- RELATED MORBIDITY AND MORTALITY EXCEEDS $ 136 BILLION