Drug Toxicity

Drugs can produce toxic effects in addition to pharmacological actions. No drugs are free from toxic effect. With some drugs, toxic effects may be minor where they may be serious with certain drugs.

Therapeutic index: It is defined as the ratio of median lethal dose to median effective dose.

LD50 (Median lethal dose) = It is the dose which kills half of the population of the animal tested.

ED50 (median effective dose) = It is the dose which produces the desired response in half of the population tested.

The therapeutic index provides an idea about the safety of the drug. Higher the therapeutics index, safer is the drug.

Therapeutic index of penicillin is 150, indicating that the drug is relatively safe in terms of toxic effects of over dosage. Digoxin has low (1.5-2) and the margin of safety is narrower.

In animals a medication of this concept can be applied. The therapeutic index can be calculated as:

Drug Toxicities: Adverse drug reactions may be defined as under

1. Pharmacologic Adverse Reactions

Extension of therapeutic effect.

Non-therapeutic adverse effects.

2. Non-Pharmacological Adverse Reactions

Hypersensitivity (drug allergy).

Idiosyncrasy (pharmacogenetics).

3. Disease Related Adverse Reactions

Multiple drug reactions.

Miscellaneous adverse reactions.

The Following are the Various Toxicities Produced by the Drugs:

Intolerance: It is defined as the inability of an individual to tolerate a drug. It may occur due to metabolic disorders like enzyme deficiency or due to allergic reactions. E.g. – One tablet of chloroquine, may cause vomiting and abdominal pain in an occasional patient.

Idiosyncrasy: It is genetically determined abnormal reactivity to a chemical. Certain adverse effects of some drugs are largely restricted to individuals with a particular genotype. E.g.-Barbiturates cause excitement and mental confusion in some individuals. Quinine/Quinidine cause cramps, asthma, diarrhoea, and vascular collapse in some patients.

Blood Dyscrasias: It is mostly due to the toxic effects of a drug on the bone marrow. E.g. Chloramphenicol. It occurs in the form of leucopenia, agranulocytosis, aplastic anemia and hemolytic anaemia.

Hepatotoxicity: Most drugs are concentrated in the liver. Hence damage of this organ is a common form of toxicity. E.g. – Primaquine.

Nephrotoxicity: Drugs like sulfonamides produce damage to kidney in the form of crystalluria, albuminuria and haematuria

Endocrine Disturbances: On prolonged administration, reserpine can produce endocrine disturbances leading to reduction infertility in women.

Electrolyte Disturbances: Corticosteroids like hydrocortisone may produce sodium retention and edema.

Skin Reaction: Drugs taken systemically or applied locally can produces skin rashes. The rashes are of different form like dermatitis,urticaria. The same drug may produce different kind of rashes in different people.

Behavioral Toxicity: AT times drugs may alter the normal behavior. E.g.-Atropine produces euphoria, excision, and mania to toxic dose.

Drug Induced Diseases: At times drugs by themselves can produce certain disease. E.g.-Parkinsonism caused by reserpine.

Photosensitivity: It is a reaction resulting from drug induced sensitization of the skin to UV rays. The reactions are of two types –

Photo Toxic: Drug or its metabolite accumulates in the skin, absorbs light and under goes a photochemical reaction resulting tissue damage, erythema (reddening of skin), edema, blistering and hyper-pigmentation. E.g.-Sulfonamides, thiazides and phenothiazine.

Photo Allergic: Exposures to light of longer wave length produces a papular (lesion) or eczematous contact dermatitis. E.g.-griseofulvin, chloroquine, chlorpromazine.

Carcinogenesis: It refers to capacity of a drug to cause cancer genetic defects respectively. Drugs implicated in these adverse effects are anti cancer drugs, radioisotopes, estrogens, tobacco.

Addiction: This is also called drug dependence which involves both psychological and physical dependence for a drug. It is a state of periodic or chronic intoxication produced by repeated drug administration.

The characteristics of drug addiction are –

An over powering desire to take the drug.

A tendency to increase the dose.

Development of psychic and physical dependence.

Detrimental effect on the individual and society.

Teratogenic effect: Drugs when administered to pregnant women are likely to produces foetal abnormalities. The placenta does not strictly constitute a barrier and any drug can cross it to a greater or lesser extent.

Drug Induced Sexual Dysfunction: A wide variety of drugs have been implicated as causing sexual dysfunction. Drug may cause dysfunction by affecting the autonomic nervous system, by causing CNS depression, or by altering endocrine function. The effects of various drugs on libido (sex drive), potency (erection) and ejaculation. E.g. – Alcohol, amphetamine, prazosin, clofibrate, nicotine, cocaine, cannabis.

Acute Poisoning: A poison is a substance which when consumed endangers life due to derangement of certain vital physiological functions. Acute poisoning in adults usually deliberate and self inflicted. Drugs employed include hypnotics, anxiolytics, anti-depressant, and analgesic.

Anaphylactic Shock: An extreme and generalized allergic response leading to widespread release of histamine characterized by edema, constriction of bronchioles, heart failure, circulatory collapse and even death.

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