Introduction To The Introduction To The Clinical PharmacyClinical Pharmacy

ByByAmgad A. Ragab, Pharm D, CCPAmgad A. Ragab, Pharm D, CCP

New York University Medical CollegeNew York University Medical CollegeNew York University Cancer CenterNew York University Cancer Center

New York USANew York USA

Human BodyHuman 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 OrgansHuman 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 ChemistryHuman 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 STUDYCASE 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 MANAGEMENTCASE 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 DISCOVERYMEDICAL 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 ACTIONMECHANISM 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

InterventionIntervention

• 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)ADVERSE DRUG EVENT (ADE)

• DefinitionAny injury that results from the use of a drug

CLASSIFICATIONS OF ADECLASSIFICATIONS 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 ErrorAny 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.)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 INTERVENTION TO RESOLVE PATIENT’S DRUG THERAPY PATIENT’S DRUG THERAPY

PROBLEMPROBLEM• 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 ADRCLASSIFICATION OF ADR

• Type I: Augmented reactions Related to pharmacologic effects eg: hypoglycemic coma from insulin hypoprothrombinemia from warfarin80-85% of all ADRs, considered predictable

• Type II: Bizarre reactionsRelated to hypersensitivity or immune mediated reactions 15-20% of all ADRs, considered unpredictable

ADEs & HEALTH CARE ADEs & HEALTH CARE SETTINGSSETTINGS

• 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.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.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 STATISTICSADEs 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%

CONCLUSIONCONCLUSION

• THE ANNUAL COST OF DRUG- RELATED MORBIDITY AND MORTALITY EXCEEDS

$ 136 BILLION