ADVERSE DRUG

REACTIONS

OVERVIEW

STATISTICS

5% of adults are allergic to one or more medications

6 – 10% of ADRs result from a drug allergy 3% of hospital admissions are due to ADRs 28% of ADRs are preventable Drugs associated with ADRs: 29% analgesics,

10% sedatives, 9% antibiotics, and 7% antipsychotics.

PGH: Antibiotics (35%), anti-TB meds (34%), anticonvulsants and ASA/NSAIDS (10% each)

ADRs: 4th Leading Cause of Death

Study: Drug reactions kill an estimated 100,000 a year

April 14, 1998

What are Adverse Drug Reactions (ADRs)?

any response to a drug which is noxious and unintended and which occurs at doses used in man for prophylaxis, diagnosis or therapy

What is an adverse drug experience?

An undesirable drug effect, whether harmless, resulting from medications administered in a dosage normally given.

It becomes an adverse drug reaction when it is reported and subsequently evaluated to be secondary to the drug usage.

Key points to remember

ADRs

Common Causes of ADRs

Failing to take the correct dosages at the correct times

Overdosing Allergies to chemical components of the medicine Combining the medicine with alcohol Taking other drugs or preparations that interact with

the medicine Taking a medicine that was prescribed for someone

else.

Causes of ADR Pharmaceutical causes

decreasing particle size or changing excipients

Pharmacokinetic causes diazepam aminoglycosides

Pharmacodynamic causes increased sensitivity of target organs

in the body to drugs

Factors affecting Adverse Drug Reactions : Patient-related factors

Age Sex Genetic influences Concurrent diseases (renal,liver, cardiac) Previous adverse drug reactions Compliance with dosing regimen Total number of medications Misc. (diet, smoking, environmental exposure)

Factors affecting Adverse Drug Reactions :

Drug-related factors: Dose Duration Inherent toxicity of the

agent Pharmacodynamic

properties Pharmacokinetic properties

Six Classifications of ADR

Type A Type B Type C Type D Type E Type F

(Augmented)(Bizarre)(Continuous)(Delayed)(Ending of Use)(Failure of Efficacy)

Type A Reactions or Augmented Activity (pharmacological) of a drug

Extension Effects Adverse Effects

Extension Effects

predictable dose-related responses prevention: Adjustment of dosage djustment of dosage

regimenregimen

Examples of Extension Effects

Benzodiazepines Furosemide

Heparin, warfarin

insulin

– sedation– water and electrolyte

imbalance– spontaneous bleeding

– hypoglycemia

Adverse Effects

predictable, dose-dependent reactions unrelated to the goal of therapy

often produced by the same drug-receptor interaction responsible for the therapeutic effect, differing only in the tissue/s or organ/s affected

Example of Adverse Effects

INH, Rifampicin, PZA streptomycin captopril simvastatin nitrates propranolol tetracycline

– hepatotoxicity– ototoxicity, nephrotoxicity

– cough– rhabdomyolysis– headache– bronchial asthma– hypoplasia of the teeth

Type B Reactions or Bizarre

aBnormal effects Unrelated from the

drug’s known pharmacological actions

Characteristics of Bizarre Reactions no formal dose-response curve (penicillin

hypersensitivity – anaphylaxis) reaction disappears on discontinuation of the

drug recognizable as an immunological reaction undetectable during conventional testing little or no relation to the usual

pharmacological effects of the drug delay between exposure to the drug and the

occurrence of the subsequent adverse reaction

Example of Bizarre Reactions

Hypersensitivity reactions Stevens-Johnson’s Syndrome Hemolytic anemia

Type C Reactions or Continuous

long term effects are usually related to the dose and duration of treatment

Examples ethambutol NSAIDs

Type D Reactions or Delayed

Carcinogenesis

Teratogenesis

Examples: thalidomide, vitamin A

Type E Reactions or Ending of Use Withdrawal Syndromes

Examples: benzodiazepines clonidine corticosteroids opioids

– rebound insomnia, agitation

– rebound hypertension– acute adrenal insufficiency– narcotic withdrawal

Type F Reactions or Failure of Efficacy

Counterfeit medicines Underdosing of medications Drug interactions

Exercises

Example #1

An 8-day old female was diagnosed to have neonatal tetanus. Diazepam was used as the anticonvulsant with a dose of 0.2 mg/kg/dose q 4hrs. With persistence of spasms, the dose was increased to 0.5 mg/kg/dose up to the maximum dose of 1 mg/kg/dose but still no improvement. Higher doses of the same brand was also ineffective. The patient was later started on Midazolam drip which resulted in decreased frequency of spasms.

Type F

Example #2

A patient was maintained on clonidine 150 mcg BID and Aspirin 80 mg tab OD. Then the patient stopped his medications due to financial constraints. The patient suddenly experienced headache, dizziness and flushing due to increased blood pressure.

Type E

Example #3

A TB patient was started with fixed-dose anti-TB drugs for 6 months. After several days, the patient was noted for rashes. The patient sought consult and was advised to stop his anti-TB drugs. This resulted to remission of the rashes.

Type B

Example #4

A patient with chronic stable angina was given isosorbide dinitrate. After taking ISDN, the patient experienced dizziness and headache. The dose of ISDN was reduced which resulted to improvement of the patient’s status.

Adverse Effect

ADR REPORTING

Why report ADRs?

To prevent drug-induced human suffering

To avoid financial risks associated with unexpected risks

June 22, 1963 as amended on May 22, 1987 Republic Act 3720 “Food, Drugs and Devices and Cosmetics Act” Creation of Food and Drug Administration now Bureau of Food and DrugsApril 20, 1994 BFAD Memorandum Circular No. 5 s. 1994 Submission of ADR reports by pharmaceutical establishments and parties concernedJune 30, 1994 Department Order No. 345 - I s. 1994 Creation of National Adverse Drug Reaction Advisory Committee (NADRAC)

GOVERNMENT POLICY ON ADR REPORTING

Reports from

ParticipatingHospitals

Reports from

Private Practitioners

Reportfrom

Drug Mfr.Traders/Outlets

Reportson

ClinicalInvestiga-

tions

Reportsfrom

RegulatoryAuthorities

Reports fromInt’lADR

Centers

BFAD ADR UNIT

NADRAC WHO Collaborating Center

Director - BFAD

Secretary ofHealth - DOH

ADR Monitoring System

REPORTING SCHEMEREPORTING SCHEME

NADRACNADRAC

(Trend Analysis) (Trend Analysis)

CASECASE

Reporter Fills Out a Reporter Fills Out a FormForm

Hospital Hospital

Therapeutic Therapeutic CommitteesCommittees

ADRMP Office ADRMP Office

(Central Database)(Central Database) WHOWHO

WHOWHO

THE PGH ADVERSE DRUG REACTION REPORTING SCHEME

How do we report ADRs?

STEP 1 : Fill out the RED ALERT CARDSPGH FORM # P – 60170

PGH ADVERSE DRUG SURVEILLANCE ALERT CARD

(Clip this on chart front cover)

Name of patient:___________________________________Ward & Bed No.:__________________________________Name of suspect drug:______________________________Manufacturer:_____________________________________Lot/ Code No.:__________ (Retain empty vial or container)Describe the reaction:_______________________________ __________________________________________________________________________________________________Reporter: _________________________________________

(Please Print)

PLEASE NOTIFY: CENTRAL BLOCK PHARMACYLoc. 3163 / 3170

How do we report ADRs?

STEP 2: Complete the ADR REPORT FORM

The Resident - in - charge of the patient shall

complete the necessary report of ADR

circumstances.

STEP 2: Complete the ADR REPORT FORM

The Resident - in - charge of the patient shall

complete the necessary report of ADR

circumstances.

How do we report ADRs?

STEP 3: Submit the red alert card and the ADR report form to the Central Block Pharmacy for proper referral.

STEP 4: The Pharmacy will then compile the reports for review of the ADR Subcommittee and submission to the Bureau of Food and Drugs (BFAD).

Pharmacist

The ADR Report Form should include the following:

brand name of the suspect drug

the manufacturer (if generic)

the lot and batch number.

It should be done in duplicate.

ALL REPORTS ARE CONFIDENTIAL

IMPORTANT!!!!

Common reports rash caused by Oxacillin red face, fever secondary to Vancomycin

Uncommon reports hair loss due to anti thyroid agents neuroleptic malignant syndrome with risperidone

Examples of Reported ADRs

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

1. Critically review the total condition of the patient. Be particularly careful when you prescribe to children, elderly, seriously ill, pregnant patients and those with renal, cardiac or liver diseases.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

2. Use as few drugs as possible. Balance the seriousness of possible reactions against the beneficial effects of each drug that is being considered.

3. Know well the drugs that you use. Compare the efficacy and safety of each of the available competitive medications that appear to be worthy of consideration for the patient.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

4. Do not change too readily from one drug you know to one you do not know. If you decide to use a new drug, know that drug.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

5. Do not hesitate to use textbooks and other references providing information on drug reaction and interaction.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

6. Be especially careful when prescribing drugs known to exhibit a large variety of reactions/ interactions.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

7. Be aware of interactions with certain foods, alcohol and even with household chemicals.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

8. Regularly make an inventory of the drugs your patient is receiving.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

9. Review your patient regularly for all the drugs used and especially those bought without prescriptions.

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

TEN COMMANDMENTS to reduce ADVERSE DRUG REACTIONS

10. If your patient shows signs and symptoms not clearly explained by the course of illness, think of adverse drug reaction.