Paper 1 - Pharmacology Overview

Paper 1 - Pharmacology

• Drug Targets: Drugs can act on receptors (activating or blocking), ion channels, enzymes, or transporters.

• Receptors on Cell Membranes:

• Ligand-gated ion channels (e.g., nicotinic acetylcholine receptors)

• G protein-coupled receptors (e.g., beta-adrenergic receptors)

• Example Drug with cGMP as Secondary Messenger: Nitroglycerin, Sildenafil (Viagra).

• pH and Drug Ionization: The pH of a medium affects a drug's ionization, impacting its solubility, absorption, and distribution. This is described by the Henderson-Hasselbalch equation.

• Drugs That Induce Liver Enzymes: Antiepileptic drugs (phenytoin, phenobarbital), anti-tubercular drugs (rifampin, rifabutin), and antiretroviral drugs (efavirenz, nevirapine)

• Enzyme Induction Clinical Relevance:

• Reduced efficacy of oral contraceptives

• Sub-therapeutic effect of warfarin

• Drugs That Change Kinetics (1st order to 0 order):

• Phenytoin

• Ethanol

• Drugs Requiring Therapeutic Monitoring:

• Warfarin

• Digoxin

• Dopamine vs. Dobutamine:

• Dopamine: Acts on dopamine and beta-1 adrenergic receptors (at moderate doses), alpha-adrenergic receptors (high doses) and is used in shock to improve blood pressure. It increases heart rate significantly and has dose-dependent effects on blood vessels (vasodilation, mixed effects, vasoconstriction).

• Dobutamine: Primarily a beta-1 adrenergic agonist with minimal effect on alpha or dopamine receptors. Used in heart failure to increase cardiac output. It minimally increases heart rate and primarily improves contractility and has minimal effect on blood vessels.

• Adrenaline Uses: Anaphylaxis, asthma, cardiac arrest, and local anesthesia.

• Sites to Avoid Mixing Adrenaline with Local Anesthetics: Fingers, nose, toes, eyes and penis

• Noradrenaline Uses: Hypotension and shock, and cardiac arrest

• Prazosin (Alpha Blocker) Uses: Hypertension and benign prostatic hyperplasia.

• Labetalol (Alpha + Beta Blocker) Uses: Hypertension, hypertensive emergency, angina, and heart failure.

• Potency and Efficacy:

• Potency: The amount of drug needed to produce a given effect (lower dose = higher potency).

• Efficacy: The maximum effect a drug can produce (regardless of dose).

• Anticholingeric substitutes for ophthalmology: Tropicamide, cyclopentolate, homatropine

• Atropine substitutes for respiratory conditions: Ipratropium, tiotropium, oxitropium, glycopyrrolate

• Bethanecol (cholinergic agonist) uses: Urinary retention, postoperative ileus, and neurogenic bladder

• Adverse effect vs. Side effect:

• Adverse effect: Serious, life-threatening, unpredictable effects.

• Side effect: Milder, non-harmful effects, usually predictable, and occur at therapeutic doses.

• ED50, TD50, LD50:

• ED50 (Effective Dose 50): Dose of a drug causing a therapeutic effect in 50% of the population

• TD50 (Toxic Dose 50): Dose of a drug causing toxic effects in 50% of the population

• LD50 (Lethal Dose 50): Dose of a drug causing death in 50% of the population.

• Acyclovir adverse effects: GI disturbance, renal toxicity, and neurotoxicity

• Viral Hepatitis drugs:

• Hepatitis B: Tenofovir, entecavir, lamivudine, adefovir, pegylated interferon

• Hepatitis C: Sofosbuvir, ledipasvir, daclatasvir, ribavirin

• Hepatitis D: Pegylated interferon

• Hepatitis E: Ribavirin (certain cases)

• Antifungal drugs:

• Polyenes (amphotericin B, nystatin)

• Azoles (clotrimazole, ketoconazole, fluconazole, itraconazole, voriconazole)

• Echinocandins (caspofungin, micafungin, anidulafungin)

• Allylamines (terbinafine, naftifine, butenafine)

• Flucytosine

• Griseofulvin

• Topical antifungal (terbinafine, clotrimazole, miconazole, econazole, ciclopirox, undecylenic acid)

• Cephalosporin Uses: Respiratory tract infection, UTIs, skin and soft tissue infection, surgical prophylaxis.

• 3rd Generation Cephalosporins: Ceftriaxone, Cefotaxime, Ceftazidime, Cefdinir, Cefixime, Cefpodoxime, Cefoperazone, Ceftibuten

• NSAIDs with high anti-inflammatory properties: Indomethacin, Diclofenac

• NSAIDs with high analgesic properties: Ibuprofen, Naproxen

• Aspirin MOA (low doses): Irreversibly acetylates COX-1, reducing thromboxane A2 production, preventing platelet aggregation.

• Selective COX-2 inhibitors uses: Osteoarthritis, Rheumatoid arthritis

• Mefenamic acid uses: Pain relief, anti-inflammatory

• NSAID side effects: GI irritation, renal impairment, and cardiovascular risks.

• NSAID contraindications: Active peptic ulcer disease, renal impairment

• Aspirin uses based on dose:

• Low dose: cardiovascular protection

• Moderate dose: pain relief

• High dose: anti-inflammatory

• Methotrexate MOA: Inhibits dihydrofolate reductase (DHFR), interfering with nucleotide synthesis for rapidly dividing cells.

• Methotrexate adverse effects: Bone marrow suppression, hepatotoxicity, mouth ulcers, and GI distress

• Allopurinol MOA: Inhibits xanthine oxidase, preventing uric acid production.

• Infliximab uses: Rheumatoid arthritis, Crohn's disease, ulcerative colitis.

• Monoclonal antibodies used to treat Rheumatoid arthritis:

• Infliximab (targets TNF-alpha)

• Adalimumab (targets TNF-alpha)

• Rituximab (targets CD20 antigen in B-cells)

• Tocilizumab (targets IL-6 receptor)

• Hydroxychloroquine MOA: Mechanism to reduce inflammation in rheumatoid arthritis

• Hydroxychloroquine adverse effect.: Retinopathy, nausea, and vomiting

• Neuromuscular blockers: Non-depolarizing (competitive blockers), depolarizing (agonists)

• Non-depolarizing neuromuscular blockers: Pancuronium, vecuronium, rocuronium, atracurium

• Depolarizing neuromuscular blockers: Succinylcholine

• Succinylcholine interaction with genetic makeup: Individuals with pseudocholinesterase deficiency experience a prolonged neuromuscular blockade.

• Interactions of aminoglycosides and non-depolarizing neuromuscular blockers: Aminoglycosides enhance the effects of non-depolarizing neuromuscular blockers by inhibiting acetylcholine release.

This quiz focuses on essential concepts of pharmacology, including drug targets like receptors, ion channels, and the impact of pH on drug ionization. It also covers examples of drugs and their interactions with enzymes, as well as the clinical relevance of enzyme induction. Test your knowledge on these fundamental pharmacological principles!