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

2. 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 : $

3. 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 = $ each ejaculation

4. Human Chemistry Iron $ 0.30 Potassium $ 5.95
Carbon $ Calcium $ 0.18
Chloride $ Phosphours $ 7.12
Iodide $ Sulphur $ 1.60
Zinc $ Sodium $ 0.11
TOTAL $ 17.00

5. 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

6. 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

7. 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

9. 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

10. 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

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

12. 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

13. 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)

15. 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

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

17. 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

18. 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

19. 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%

20. 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%

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