"An appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product."
- Adverse effect is ‘any undesirable or unintended consequence of drug administration’. It includes all kinds of noxious effect—trivial, serious or even fatal.
- Another term ‘adverse drug event’ (ADE) mean ‘any untoward medical occurrence that may present during treatment with a medicine, but which does not necessarily have a causal relationship with the treatment’.
- Drugs are capable of producing adverse effects, and whenever a drug is given a risk is taken. The magnitude of risk has to be considered along with the magnitude of expected therapeutic benefit in deciding whether to use or not to use a particular drug in a given patient.
- Adverse effects may develop promptly or only after prolonged medication or even after stoppage of the drug.
- They are more common with multiple drug therapy and in the elderly.
Adverse effects have been classified in many ways.
1. Predictable (Type A or Augmented) reactions
- These are based on the pharmacological properties of the drug, which means that they are augmented, but a qualitatively normal response to the drug; including side effects, toxic effects, and consequences of drug withdrawal.
- They are more common, dose-related and mostly preventable and reversible.
2. Unpredictable (Type B or Bizarre) reactions
- These are based on the peculiarities of the patient and not on the drug’s known actions; including allergy and idiosyncrasy. They are less common, often non-dose related, generally more serious and require the withdrawal of the drug.
- Some of these reactions can be predicted and prevented if their genetic basis is known and a suitable test to characterize the individual’s phenotype is performed.
Severity of adverse drug reactions
Minor: No therapy, antidote or prolongation of hospitalization is required.
Moderate: Requires change in drug therapy, specific treatment or prolongs hospital stay by at least one day.
Severe: Potentially life-threatening, cause permanent damage or requires intensive medical treatment.
Lethal: Directly or indirectly contributes to death of the patient.
Prevention of adverse effects to drugs
- Avoid all inappropriate use of drugs in the context of the patient’s clinical condition.
- Use appropriate dose, route and frequency of drug administration based on patient’s specific variables.
- Elicit and take into consideration previous history of drug reactions.
- Elicit history of allergic diseases and exercise caution (drug allergy is more common in patients with allergic diseases).
- Rule out possibility of drug interactions when more than one drug is prescribed.
- Adopt correct drug administration technique
- Carry out appropriate laboratory monitoring
Types of Adverse drug effects
Side effects
- These are unwanted but often unavoidable pharmacodynamic effects that occur at therapeutic doses. Generally, they are not serious, can be predicted from the pharmacological profile of a drug and are known to occur in a given percentage of drug recipients. Reduction in dose, usually ameliorates the symptoms.
- A side effect may be based on the same action as the therapeutic effect. The side effect may also be based on a different facet of action.
- An effect may be therapeutic in one context but side effect in another context, e.g. codeine used for cough produces constipation as a side effect, but the latter is its therapeutic effect in traveler's diarrhea.
Secondary effects
- These are indirect consequences of a primary action of the drug.
Toxic effects
- These are the result of the excessive pharmacological action of the drug due to overdosage or prolonged use. They result from functional alteration or drug-induced tissue damage.
Poisoning
- Poisoning implies harmful effects of a chemical on a biological system. It may result from large doses of drugs because ‘it is the dose which distinguishes a drug from a poison’. Poison is a ‘substance which endangers life by severely affecting one or more vital
- functions’. Not only drugs but other household and industrial chemicals, insecticides, etc. are frequently involved in poisonings.
- Specific antidotes such as receptor antagonists, chelating agents or specific antibodies are available for few poisons. General supportive and symptomatic treatment is all that can be done for others, and this is also important for poisons which have a selective antagonist.
Intolerance
- It is the appearance of characteristic toxic effects of a drug in an individual at therapeutic doses. Examples: A single dose of triflupromazine induces muscular dystonias in some individuals, especially children.
Idiosyncrasy
- It is genetically determined abnormal reactivity to a chemical. The drug interacts with some unique features of the individual, not found in the majority of subjects, and produces an uncharacteristic reaction.
- e.g.: Barbiturates cause excitement and mental confusion in some individuals
Drug allergy
- It is an immunologically mediated reaction producing stereotype symptoms which are unrelated to the pharmacodynamic profile of the drug, generally occur even with much smaller doses and have a different time course of onset and duration. This is also called drug hypersensitivity.
- Allergic reactions occur only in a small proportion of the population exposed to the drug and cannot be produced in other individuals at any dose. Prior sensitization is needed and a latent period of at least 1–2 weeks is required after the first exposure.
Photosensitivity
- It is a cutaneous reaction resulting from drug induced sensitization of the skin to UV radiation.
- The reactions are of two types:
- Phototoxic Drug or its metabolite accumulates in the skin, absorbs light and undergoes a photochemical reaction followed by a photobiological reaction resulting in local tissue damage (sunburn-like), i.e. erythema, edema, blistering which have fast onset and shorter duration after exposure ends. This is followed by hyperpigmentation and desquamation.
- Photoallergic Drug or its metabolite induces a cell mediated immune response which on exposure to light of longer wave lengths (320–400 nm, UV-A) produces a papular or eczematous contact dermatitis like picture that may persist long after exposure.
Drug dependence
- Drugs are capable of altering mood and feelings are liable to repetitive use to derive euphoria, recreation, withdrawal from reality, social adjustment, etc.
- Drug dependence is a state in which use of drugs for personal satisfaction is accorded a higher priority than other basic needs, often in the face of known risks to health.
- The following may serve to describe different aspects of the problem.
Psychological dependence
It is developed when the individual believes that optimal state of wellbeing is achieved only through the actions of the drug.
Physical dependence
It is an altered physiological state produced by repeated administration of a drug which necessitates the continued presence of the drug to maintain physiological equilibrium.
Drug abuse
- Refers to use of a drug by self medication in a manner and amount that deviates from the approved medical and social patterns in a given culture at a given time. The term conveys social disapproval of the manner and purpose of drug use. For regulatory agencies, drug abuse refers to any use of an ilicit drug.
- The two major patterns of drug abuse are:
- Continuous use: The drug is taken regularly, the subject wishes to continuously remain under the influence of the drug, e.g. opioids, alcohol, sedatives.
- Occasional use: The drug is taken off and on to obtain pleasure or high, recreation (as in rave parties) or enhancement of sexual experience, e.g. cocaine, amphetamines, psychedelics, binge drinking (alcohol), cannabis, solvents (inhalation), etc.
Drug addiction
- It is a pattern of compulsive drug use characterized by overwhelming involvement with the use of a drug.
Drug habituation
It denotes less intensive involvement with the drug, so that its withdrawal produces only mild discomfort.
Drug withdrawal reactions
- Sudden interruption of therapy with certain other drugs also results in adverse consequences, mostly in the form of worsening of the clinical condition for which the drug was being used.
Teratogenicity
- It refers to the capacity of a drug to cause foetal abnormalities when administered to the pregnant mother. The placenta does not constitute a strict barrier, and any drug can cross it to a greater or lesser extent.
Mutagenicity and Carcinogenicity
- It refers to capacity of a drug to cause genetic defects and cancer respectively. Usually oxidation of the drug results in the production of reactive intermediates which affect genes and may cause structural changes in the chromosomes.
- Covalent interaction with DNA can modify it to induce mutations, which may manifest as heritable defects in the next generation.
Drug induced diseases
- These are also called iatrogenic (physician-induced) diseases, and are functional disturbances (disease) caused by drugs which persist even after the offending drug has been withdrawn and largely eliminated, e.g.: Peptic ulcer by salicylates and corticosteroids
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