Test: Autacoids - 3 - NEET PG MCQ

acetylsalicylic acid (aspirin) acts as an irreversible inhibitor of the COX enzyme. This leads to the suppression of PG and TX production.

• At low doses (40-325 mg), it provides an antiplatelet effect.
• This medication exhibits saturation kinetics at elevated doses, meaning the kinetics shift from first order to zero order.
• Consequently, at high doses, the quantity of the drug excreted remains constant.
• This indicates that clearance is not constant.

PGE₂ and PGI₂ induce renal vasodilation, promote natriuresis, and enhance water clearance by inhibiting the effects of ADH. Loop diuretics function in part by boosting COX stimulation; consequently, NSAIDs reduce the diuretic effectiveness of these medications.

Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that functions through the irreversible inhibition of the cyclooxygenase enzyme, which reduces the production of prostaglandins.

Antiplatelet medications (such as aspirin and clopidogrel) extend the duration of bleeding. Anticoagulant medications increase the clotting time.

• Medications that affect the intrinsic pathway (for example, heparin) prolong the aPTT.
• Medications that affect the extrinsic pathway (such as warfarin) prolong the PT.

The thrombin time is extended in situations of afibrinogenemia and dysfibrinogenemia.

The natural prostaglandin present in the body is PGE₂. In contrast, misoprostol and alprostadil are synthetic prostaglandins that act as analogues of PGE₁.

COX-2 is an inducible enzyme, while COX-1 serves as a constitutional (housekeeping) enzyme.

Piroxicam serves as a long-lasting analgesic owing to its enterohepatic circulation. A single daily dose is typically adequate.

Consuming 10g (ten grams) of paracetamol can lead to acute poisoning. The likelihood of death and severe liver failure increases significantly if plasma concentrations exceed:

• 200 µg/ml at 4 hours
• 30 µg/ml at 15 hours

Administering gastric lavage and activated charcoal at 6 hours will likely be ineffective, as the majority of the medication will have already been absorbed by that point.

PGE₂ primarily facilitates the softening of the cervix and is employed for cervical ripening, while PGF₂ acts as an oxytocic agent and can be used for inducing abortion.

PGI₂ analogues (such as epoprostenol and treprostinil) are employed in the management of pulmonary hypertension. PGE₁ analogues are utilised for:

• First trimester abortion (misoprostol)
• Impotence (alprostadil)
• Maintaining the patency of the ductus arteriosus (alprostadil)

TXA₂ is synthesised within the platelets through the action of TXA₂ synthetase. It arises from cyclic endoperoxides (PGG₂/H₂) with the assistance of the enzyme cyclooxygenase. Aspirin inhibits its production by irreversibly blocking the cyclooxygenase enzyme. TXA₂ promotes platelet aggregation, consequently making it prothrombotic.

Symptoms of aspirin poisoning – At anti-inflammatory doses (3-6 g/day), a syndrome known as Salicylism can occur, which includes:

• dizziness
• tinnitus
• vertigo
• excitement
• mental confusion
• reversible hearing impairment

The dosage should be adjusted to just below the level that triggers these symptoms, with tinnitus serving as a useful indicator. In cases of severe poisoning, metabolic acidosis, hyperthermia, and acidotic breathing can be observed. Aspirin affects platelet function by inhibiting the cyclooxygenase pathway. The lethal dose for adults ranges from 15-30 g, but it is notably lower in children.

Aspirin irreversibly inhibits COX by acetylating a specific serine residue; the restoration of COX activity relies on the production of new enzyme. Other NSAIDs such as indomethacin and diclofenac are competitive and reversible COX inhibitors, with the return of activity depending on their dissociation from the enzyme, which is influenced by the pharmacokinetic properties of the compound. Corticosteroids like betamethasone function by inhibiting phospholipase A₂.

Alprostadil (PGE₁) and prednisolone do not block the cox enzyme, while aspirin serves as an irreversible inhibitor of this enzyme.

LTC₄, D₄ and E₄ are identified as slow-reacting substances involved in anaphylaxis because they may lead to bronchoconstriction.

It is a potent anti-inflammatory agent. It functions by blocking the production of PG, TX, and LT through the suppression of the phospholipase A₂ enzyme. Nevertheless, its principal mechanism for anti-inflammatory effects is the inhibition of chemotaxis.

Non-selective COX inhibitors used over a prolonged period are linked to peptic ulcer disease. These medications should be avoided in patients with a history of PUD.

On the other hand, selective COX-2 inhibitors such as celecoxib are considered safe in this context.