ADVERSE DRUG REACTION (ADR)

Adverse Drug Reaction (ADR) is a response to a drug that is noxious and unintended that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of disease or for the modification of physiological function. It is a result of the intrinsic properties of the drug and cannot be prevented.



There are different types of it that used to identify them in the expand of treatment. They are, as follows:

• Type A or Augmentation
• Type B or Bizarre
• Type C or Continuous
• Type D or Delayed
• Type E or End of use
• Type F or Failure of efficacy
  

TYPE A (AUGMENTATION)
 It is a common, predictable and dose-related adverse drug reaction. And can be the dependent on clearance of the drug in the body that this drug reaction is incurred. There are two subtypes of it, either Extension Effects or Side Effects.

1. Extension Effects can be related to pharmacological activity of the drug.
   Examples:
   

• Tachycardia caused by salbutamol
  
• Hypoglycemia caused by oral sulfonylureas
  
• Sedation caused by CNS depressants
  
• Hemorrhage caused by Anticoagulants
  

2. Side Effects are not relevant to the pharmacological action of the drug.
   Examples:
   

• Opiates that causing constipation
  
• ACE inhibitors causing cough
  
• Sedation by antihistamines
  
• Headache by nitroglycerine
  

TYPE B (BIZARRE)
It is not common to drugs, unpredictable and non dose-related reaction. Does not have relevance to the pharmacological action of the drug in the body.
Subtypes are Idiosyncrasy and Hypersensitivity Reactions

1. Idiosyncrasy is a reaction basically linked and determined through the genes of the individual.
   Examples:
   

• Antipsychotic drugs having malignant hyperthermia effect.
  
• Carbamazepine, Phenytoin and Sulfonamides causing Stevens-Johnson Syndrome
  

2. Hypersensitivity Reactions are immune responses to environmental antigens and stimuli resulting into symptomatic reactions upon secondary exposure to the same antigen again. Antigen is more known to be allergen.
   Types of Hypersensitivity Reactions:
   

• Type I (Immediate or Anaphylactic Immune Response)
  

• Categorized as the most common allergic reaction because after an antigen (eg. pollen) binds onto Immunoglobulin E, which found in the surfaces of mast cells, can cause a severe reaction risky to the life of individual. Repetition of exposure to the same allergen, having cross linking of the cell-bound IgE, could cause degranulation that stimulates the release of histamines, leukotrienes and prostaglandins which are the main cause of the anaphylaxis (penicillin), inflammation, urticaria (hives), rushes , hay fever, asthma, dyspnea and etc.

• Type II (Cytotoxic Reactions)
  

• It is initiated by antibody, either Immunoglobulin G or Immunoglobulin M, directed against the antigens found on the cell membrane of a given target cell such as leukocytes and erythrocytes. It resulted to complement mediated lysis of the cell.
  Examples are: 1) Hemolytic anemia caused by Methyldopa, Aplastic Anemia when Chloramphenicol is given, and when blood transfusion procedure is made.

• Type III (Immune Complex Hypersensitivity)

• The tissue deposition of antigen-antibody complexes with complementary activation and tissue damage
  Examples are: 1) Arthus reaction stimulates through IM or SQ administration, 2) SLE caused by Hydralazine, Phenytoin, Isoniazid, and Procainamide; and 3) blood dyscrasias or serum sickness.

• Type IV (Cell-Mediated or Delayed Reaction)

• The T-lymphocytes are sensitized by an antigen releasing lymphokines after subsequent contact with the same antigen. Lymphokines induce inflammation and activate the production of macrophages.
  Examples: 1) Tuberculin Skin Test; and Contact dermatitis caused by poison ivy and nickel.

TYPE C (CONTINUOUS)

It is also uncommon but dose and time related reaction. Can be associated with the cumulative dose of the the drug that is taken or given.

Subtypes:

1. Addiction is a condition where a person takes the drug compulsively, despite of potential harm that might cause to themselves, or their desire to stop. Examples are such addiction to marijuana or opiates.
2. Dependence is a compulsion to take the drug repeatedly and experiences unpleasant symptoms if discontinued. Examples are benzodiazepines, caffeine in coffee and cocaine dependence.
   
   
   Classification of Dependence

• Physical Dependence is an occurrence when a drug has been used habitually and the body has become accustomed to its effects. The person must then continue to use the drug in order to feel normal that when absence of it will trigger symptoms of withdrawal.
• Psychological Dependence is occurred when a drug has been used habitually. The mind has become emotionally reliant to its effects, either to elicit pleasure or relieve pain, and does not feel capable of functioning without it.

3. Tolerance is the deregulation of receptor site, which the drug reduced its effect with repeated use, thus, a higher doses of it must be introduced to produce the same effect. Examples are Nicotine and prednisone.
   

TYPE D (DELAYED)

The drug reaction is manifested when a drug is used for long term.

Subtypes:

1. Carcinogenicity is the ability of any compound or substance to produce or induce tumor and cancer.
   Examples:
   Afltoxin
   Nitrosamines
   Aromatic Hydrocarbons
   Antineoplastic agents
   Heterocyclic amines
   
2. Teratogenicity is the ability of a substance to cause congenital and malformations to fetus (birth defects) when the mother is exposed it.
   Examples:
   Carbamazepine and Valproic Acid that cause neural tube defects
   Diethylstilbestrol that can increase risk of developing vaginal adenocarcinoma after puberty
   Phenytoin causing fetal hydantoin syndrome
   Streptomycin damaging the 8^th nerve ( sense of balance)
   Tetracyclines causing discoloration and defects of teeth and deformed bone growth
   Thalidomide causing phocomelia (penguin-like)
   Isotretinoin or Vitamin A powerful teratogen

TYPE E (END OF USE)

It is also uncommon. Most associated to withdrawal syndromes that generally occur shortly after stopping the drug.

Examples:

• Opiates withdrawal
• Rebound insomnia and excitation by Benzodiazepines
• Rebound hypertension (Clonidine)
• Rebound decongestant by Nasal decongestant
• Addison's disease caused by steroids

TYPE F (FAILURE OF EFFICACY)

It is unexpected failure of efficacy. It is common and dose-related. May results from:

• Drug-drug interactions
• Use of counterfeit drugs
• drug resistance
• patient's non-compliance
• wrong route of administration
• drug instability