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Tricyclic Antidepressant (TCAs) Side Effects

Tricyclic antidepressants (TCAs) are drugs used to treat depression, bipolar disorder, and other conditions such as chronic pain and insomnia. They primarily work by blocking norepinephrine and serotonin (5HT2) reuptake. They also block acetylcholine and histamine receptors which contribute to their side effect profile.⁠ ⁠ 👉🏻 Muscarinic M1 block: anticholinergic side effects including dry mouth, blurry vision, constipation, and urinary retention⁠ ⁠ 👉🏻 Histamine 1 receptor block: sedation and weight gain⁠ ⁠ 👉🏻 Adrenergic alpha block: postural hypotension, tachycardia, and erectile disfunction ⁠ ⁠ 👉🏻 Sodium channel block: QTc prolongation, arrhythmias ⁠ ⁠ 👉🏻 Serotonin uptake block: weight gain⁠

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Valproate Side Effects

💊 Valproic acid is used in seizures, bipolar disorder, and migraine prophylaxis. It works by increasing the availability of gamma (y)-aminobutyric acid (GABA), an inhibitory neurotransmitter. ⁠ ⁠ 🖇️ Divalproex sodium is a compound of sodium valproate and valproic acid. Divalproex dissociates to valproate in the GI tract. ⁠ ⁠ 🖇️ Use special caution with the combination of valproic acid and lamotrigine due to the risk of serious rash called Stevens-Johnson Syndrome. ⁠

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Warfarin Factor Half-Lives

Warfarin is an oral anticoagulant most frequently used to control and prevent thromboembolic events. ACCP recommends that patients newly started on warfarin be bridged with LMWH or unfractionated heparin for 5 days AND until therapeutic INR is achieved. 🌟High-yield fact🌟 The presence of a therapeutic INR does not confer protection from clot formation and expansion during the first few days of warfarin therapy, so if your patient’s INR is 2.0 on day 3, it is recommended to continue bridging until day 5. This recommendation is based on the fact that the anticoagulant activity of warfarin depends on the clearance of functional clotting factors already present in the body. Warfarin works by inhibiting new clotting factors from forming but requires that the old factors be cleared from the body. The clearance of these clotting factors is determined by their half-lives. The earliest changes in the International Normalized Ratio (INR) are typically noted 24 to 36 hours after a dose of warfarin is administered. These changes are due to the clearance of functional factor VII, which is the vitamin K–dependent clotting factor with the shortest half-life (6 hours: after 3-5 half-lives or 24-36 hours it will be eliminated from the body). The factor with the longest half-life, prothrombin or factor II, will take 5 days to clear from the body, hence why we need to bridge for at least 5 days AND until therapeutic INR is achieved.

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Warfarin Factors

This is a high-yield question that is often asked on exams and clinical rotations.  This mnemonic helps you remember which vitamin K-dependent factors warfarin affects. ⁠ Warfarin, brand name Coumadin, is an anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S.⁠

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