JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PHARMACOLOGY-I Previous Question Paper (October - 2020 - R08)

Toxicity studies are essential in pharmacology to determine the safety profile of a drug. These studies are categorized based on the duration of exposure and the frequency of administration.

Acute Toxicity: This involves the administration of a single dose or multiple doses of a drug within a 24-hour period. The primary objective is to determine the median lethal dose (LD50) and identify the immediate toxic effects. It helps in assessing the potential hazards of accidental overdosage and provides data for initial dose selection in clinical trials. Observations typically last for 14 days post-administration to monitor for delayed mortality or clinical signs of toxicity.

Sub-acute Toxicity: This study involves repeated administration of the drug for a period ranging from 14 to 90 days. The goal is to evaluate the cumulative effects of the drug on various organ systems, particularly the liver, kidneys, and hematopoietic system. It helps in identifying target organ toxicity, establishing a dose-response relationship, and determining the 'no-observed-adverse-effect level' (NOAEL) for sub-chronic exposure.

Chronic Toxicity: This involves long-term administration of the drug, typically for more than 90 days, often extending up to 6 months or longer, depending on the intended duration of clinical use. The study is designed to assess the safety of drugs intended for long-term or life-long therapy. It focuses on identifying potential carcinogenic, mutagenic, or organ-specific degenerative changes that may not manifest in shorter studies. These studies are conducted in at least two mammalian species, one being a non-rodent, to ensure the safety of the drug for human use over extended periods.

Anticholinergic drugs, also known as muscarinic receptor antagonists, competitively block the binding of acetylcholine to muscarinic receptors. The prototype of this class is atropine, a belladonna alkaloid.

The pharmacological actions are primarily due to the inhibition of parasympathetic activity:

1. Central Nervous System: Atropine in therapeutic doses causes mild stimulation, but high doses lead to restlessness, confusion, and hallucinations. Scopolamine has more pronounced sedative effects.
2. Eye: These drugs cause mydriasis (dilation of the pupil) by blocking the sphincter pupillae muscle and cycloplegia (paralysis of accommodation) by blocking the ciliary muscle, leading to blurred vision and increased intraocular pressure.
3. Cardiovascular System: They cause tachycardia by blocking the vagal inhibitory effect on the SA node. At low doses, a transient bradycardia may occur due to central vagal stimulation.
4. Respiratory System: They induce bronchodilation and reduce bronchial secretions, which is useful in treating asthma and COPD.
5. Gastrointestinal Tract: They decrease tone and motility of the gut, resulting in constipation and delayed gastric emptying.
6. Secretions: They significantly inhibit salivary, sweat, and bronchial secretions, leading to a dry mouth (xerostomia) and dry skin.
7. Urinary Tract: They relax the detrusor muscle and increase the tone of the internal sphincter, which can cause urinary retention in patients with prostatic hypertrophy.

Therapeutic uses include pre-anesthetic medication to reduce secretions, treatment of bradycardia, management of organophosphate poisoning, relief of peptic ulcer symptoms (though less common now), and use in ophthalmology for refraction testing. Common adverse effects include dry mouth, blurred vision, tachycardia, constipation, and urinary retention, summarized by the mnemonic: "Mad as a hatter, blind as a bat, red as a beet, hot as a hare, and dry as a bone."