ADVERSE DRUG REACTIONS

Khent P. Alcantara, RPh

Faculty - College of Pharmacy
Our Lady of Fatima University - Antipolo Philippines
Email: kpalcantara@fatima.edu.ph

TYPES OF ADR  hemolytic anemia (G6PD + Antimalarials or Sulfonamides)

AUGMENTED  Stevens-Johnson Syndrome (Carbamazepine, Phenytoin,
Sulfonamides)
- common BIZARRE
- predictable
- dose-related • 2. Hypersensitivity Reactions - immune responses to environmental
AUGMENTED antigens resulting in symptomatic reactions upon secondary
exposure to the same antigen, more commonly referred to
Subtypes: as allergen
HYPERSENSITIVITY REACTION
1. Extension Effects - related to pharmacological activity of the drug
Type I (Immediate or Anaphylactic Immune Response)
-hypoglycemia (oral sulfonylureas)
-tachycardia (albuterol)  Most common category of allergic reaction
-diarrhea (antibiotics)  Occurs after antigen (e.g. pollen) binds onto IgE found on the
-sedation (CNS depressants) surfaces of mast cells
-bleeding (anticoagulants) HYPERSENSITIVITY REACTION
AUGMENTED
 re-exposure to the same allergen → cross-linking of the cell-
2. Side Effects - unrelated to pharmacological activity of the drug bound IgE → degranulation (release of histamines, leukotrienes
& prostaglandins)
-constipation (opiates)
-headache (nitroglycerin)  Examples:
-cough (ACE inhibitor)
-hypertrichosis (Minoxidil)  anaphylaxis (Penicillins)
-antihistamines (sedation)  hay fever
Other common side effects of drugs:  asthma
 urticaria (hives)
 Hirsutism - Minoxidil
 Alpha 1 blockers - postural hypotension
 CCB - known to cause drug induced edema HYPERSENSITIVITY REACTION
 5-HT2 antagonist- inc. serum uric acid, inc. gout attack
 Sulfoureas - Wt. gain, hypoglycemia (hyperinsulinemia) Type II (Cytotoxic Reactions)
Other common side effects of drugs:
• Initiated by antibody (IgG or IgM) directed against antigens found on
• Hydralazine - Drug induced lupus the cell membrane of a given target cell (e.g. leukocytes, erythrocytes)
→ complement-mediated lysis
• ARBs and ACE inhibitors - Hyperkalemia HYPERSENSITIVITY REACTION

• Statins - Myopathy (inc. dose) and Rhabdomyolysis (rare) Examples:

• Niacin  hemolytic anemia (Methyldopa)

 aplastic anemia (Chloramphenicol)
• Anorexia  blood transfusion reactions
• Intense cutaneous flush and pruritus Type III (Immune Complex Hypersensitivity)
• abdominal pain and nausea
• impaired glucose tolerance and hepatotoxicity (less common) - tissue deposition of antigen-antibody complexes w/ complement
activation and tissue damage
BIZARRE examples:

 uncommon 1. blood dyscrasias or serum sickness

 unpredictable 2. Arthus reaction
 not dose-related 3. SLE (Hydralazine, Phenytoin, INH, Procainamide)
 have no relation to the pharmacological action of the drug HYPERSENSITIVITY REACTION
BIZARRE
Type IV (Cell-Mediated or Delayed Type)
Subtypes:
- T-lymphocytes sensitized by an antigen release lymphokines after
1. Idiosyncracy - genetically-determined reactions subsequent contact with the same antigen

 malignant hyperthermia (Antipsychotic agents) - lymphokines induce inflammation and activate macrophages
ADVERSE DRUG REACTIONS
Khent P. Alcantara, RPh
Faculty - College of Pharmacy
Our Lady of Fatima University - Antipolo Philippines
Email: kpalcantara@fatima.edu.ph

Examples: DELAYED

1. tuberculin skin test Subtypes:

2. contact dermatitis (Poison ivy)
1. Carcinogenicity

CONTINUOUS 2. Teratogenicity

• uncommon
• dose- & time-related DELAYED
• associated with the cumulative
• dose of the drug Subtypes:

CONTINUOUS 1. Carcinogenicity

Subtypes:  ability of any substance to cause or induce cancer. Examples are:

1. antineoplastic agents
1. Addiction 2. heterocyclic amines
3. aromatic hydrocarbons
- condition where a person takes a drug compulsively, despite 4. nitrosamines
potential harm to themselves, or their desire to stop 5. aflatoxin
DELAYED
Examples:
2. Teratogenicity
- Marijuana
- Opiates • ability of any substance to cause congenital malformations or birth
CONTINUOUS defects

2. Dependence Examples:

- Compulsion to take the drug repeatedly & experiences 1. Carbamazepine & Valproic acid (neural tube defects)
unpleasant symptoms if discontinued 2. Diethylstilbestrol (increased risk of developing vaginal
adenocarcinoma after puberty)
Examples: 3. Phenytoin (fetal hydantoin syndrome)
4. Streptomycin (8th nerve damage)
- Benzodiazepines 5. Tetracyclines (discoloration & defects of teeth & altered bone
- Caffeine growth)
- Cocaine 6. Thalidomide (phocomelia)
CONTINUOUS 7. Isotretinoin (powerful teratogen)

Physical dependence Phenytoin

• Occurs when a drug has been used habitually & the body has • Fetal hydantoin syndrome
become accustomed to its effects.
1. Abnormalities of the skull and facial features
• The person must then continue to use the drug in order to feel normal, 2. Underdeveloped
or its absence will trigger the symptoms of withdrawal. 3. Cleft lip/palate
CONTINUOUS 4. Microcephaly
5. Mental retardation
Psychological dependence 6. Slowed growth
7. Congenital heart disease
• occurs when a drug has been used habitually & the mind has Alcohol consumption
become emotionally reliant on its effects, either to elicit
pleasure or relieve pain, and does not feel capable of • Contraindication in all trimesters of pregnancy
functioning without it.
CONTINUOUS FETAL ALCOHOL SYNDROME (FAS)

3. Tolerance 1. Microcephaly
2. craniaofacial abnormalities
• - Reduced effect w/ repeated use of drug; need for higher doses to 3. Growth retardation
produce the same effect 4. CVS abnormalities
5. CNS abnormalities
- example: Nicotine
ADVERSE DRUG REACTIONS
Khent P. Alcantara, RPh
Faculty - College of Pharmacy
Our Lady of Fatima University - Antipolo Philippines
Email: kpalcantara@fatima.edu.ph

Tobacco FAILURE OF EFFICACY

• Contains nicotine and carbon monoxide that may harm the fetus
 unexpected failure of efficacy
This can produce:  common
 dose-related
• fetal hypoxia
• retarded fetal growth FAILURE OF EFFICACY
• Low birth weight
• Increased spontaneous abortion May result from:
• Preterm labor and stillbirth
Cocaine 1. drug-drug interactions
2. use of counterfeit drugs
• abruptio placentae 3. drug instability
• Growth retardation 4. patient’s non-compliance
• Mental retardation 5. wrong route of administration
• Withdrawal symptoms 6. drug resistance
Drug of choice for PREGNANCY Other common ADRs

 Anti-thyroids 1. Vasodilators
o PTU (protein bound) 2. Ototoxicity (LASt QC)
 Analgesics 3. Agents that impair hearing (NAK)
o Acetaminophen 4. Vestibulotoxic agents (SG)
 Diabetes 5. Nephrotoxic
o Insulin (avoid OHAs) 6. Ocular
 Antibiotics 7. Hematopoietic
o Penicillin, cephalosphorins and erythromycin 8. Hepatic
 Anti-hypertensive 9. Cardiotoxic
o Methyldopa, Labetalol 10. Pulmonary (BAM)
o anticoagulants (heparin)
Pregnancy Category

 Category A
 No evidence of risk in later trimesters
 Safest drug to take during pregnancy
 Category B
 No risk have been hound in humans
 Category C
 Not enough research has been done to determine if these
drugs are safe
 Category D
 Adverse reactions have been found in animals
 Category X
 Demonstrated fetal abnormalities; should not be take by
pregnant women.

END OF USE

 uncommon
 withdrawal symptoms
 generally occur shortly after stopping the drug.

END OF USE examples:

1. opiate withdrawal
2. rebound insomnia & excitation (Benzodiazepine)
3. rebound hypertension (Clonidine)
4. rebound decongestant (nasal decongestant)
5. adrenal crisis (Addison’s disease)(steroids)