Pharmacy Exam Recall - Mustafa File

Cardiovascular Pharmacology and Therapy

• Angina Prevention and GTN Regimen:     * Correct regimen for the GTN patch to prevent angina is $5-15\,mg$ applied daily for $12-16\,hours$. This prevents nitrate tolerance by allowing a nitrate-free interval.     * Sublingual dose of GTN (Glyceryl Trinitrate) for acute angina: $0.3-0.6\,mg$ (or $300-600\,mcg$) every $3-4\,minutes$, with a maximum of $1800\,mcg$.     * GTN is considered safe for use during pregnancy.
• Adrenergic Agonists (Norepinephrine vs. Epinephrine):     * Norepinephrine (NE) acts on $\alpha 1$ receptors causing vasoconstriction. It decreases blood flow to skeletal muscle.     * Epinephrine (E) increases cardiac output and causes bronchodilation. It has a significant effect on $\beta 2$ receptors unlike high-dose NE.
• Digoxin Management:     * Digoxin is used for arrhythmias. When combined with Verapamil, the risk of toxicity increases because Verapamil decreases digoxin excretion; the digoxin dose may need to be reduced by approximately one-third ($33\%$).     * Hypokalemia (low potassium) increases the risk of digoxin toxicity.     * ACE inhibitors (e.g., Captopril, Perindopril) are appropriate antihypertensive choices for patients on digoxin.
• Antihypertensives and Statins:     * Ischaemic Heart Disease: Atenolol (a selective $\beta 1$ blocker) reduces infarct size and stroke risk post-MI by decreasing heart rate and myocardial oxygen demand.     * BPH Treatment: Alpha-blockers like Prazosin or Terazosin are used; they often cause postural (orthostatic) hypotension.     * Heart Failure: Maximum dose for Lisinopril in mild to moderate heart failure is $40\,mg$. Perindopril dose in CHF is typically $2-10\,mg\,daily$.     * Statins: HMG-CoA reductase inhibitors (Statins) like Simvastatin risk rhabdomyolysis or myopathy when combined with Diltiazem or Colchicine.     * CCB Class: Nifedipine is a preferred drug for hypertension combined with angina.

Central Nervous System and Neurology

• Antiepileptic Drugs (AEDs):     * Generalized Seizures: Sodium Valproate is the first-line treatment.     * Absence Seizures: Ethosuximide is the drug of choice. Carbamazepine is contraindicated.     * Myoclonic Seizures: Sodium Valproate is the drug of choice.     * Trigeminal Neuralgia: Carbamazepine is the drug of choice.     * Status Epilepticus: Diazepam, Lorazepam, and Phenytoin are used. Loading dose for Phenytoin is $15-20\,mg/kg$.     * Toxicity: Carbamazepine is associated with cardiotoxicity and hepatotoxicity. Valproate is considered the least cardiotoxic AED and is not a CYP enzyme inducer (unlike Carbamazepine and Phenytoin).     * Gingival Hypertrophy: A common side effect of Phenytoin.
• Psychotropics:     * Clozapine: Requires monitoring due to the risk of agranulocytosis.     * Olanzapine & Quetiapine: Commonly associated with weight gain and hyperglycemia.     * Tricyclic Antidepressants (TCAs): Doxepin causes anticholinergic effects (dry mouth, blurred vision, constipation). TCAs are associated with rebound salivation and hypertension upon withdrawal.     * SSRI Washout: Fluoxetine has the longest washout period due to its long half-life.     * Tardive Dyskinesia: Caused by long-term dopamine receptor blockade from antipsychotics.     * Serotonin Syndrome: Characterized by agitation, hyperreflexia, and sweating. It can occur if Duloxetine is combined with Doxepin.
• Local Anesthetics:     * Mechanism of action: Blocking voltage-gated sodium ($Na^+$) channels.     * Benzocaine and Procaine are ester-type anesthetics. Benzocaine is lipophilic and insoluble in water.

Infectious Diseases and Antibiotic Therapy

• Target Organisms and Drugs of Choice:     * Escherichia coli (UTI): Most common cause of uncomplicated UTI. First-line treatment is Cephalexin.     * Bacteroides fragilis: Anaerobe resistant to Cephalexin. Treated with Metronidazole or Cefoxitin.     * Legionella: Treated with Azithromycin, Clarithromycin, or Doxycycline.     * Chlamydia: Treated with Azithromycin or Doxycycline.     * Gonorrhea: Treated with Ceftriaxone.     * Campylobacter jejuni: Treated with Azithromycin or Ciprofloxacin.     * Mycoplasma pneumoniae (Atypical): Treated with Azithromycin or Clarithromycin; Penicillins are ineffective because Mycoplasma lacks a cell wall.     * Enterococcus faecalis: Treated with Imipenem or Meropenem.     * Diphtheria: Caused by Corynebacterium diphtheriae.
• Antibiotic Properties:     * Aminoglycosides: (e.g., Amikacin, Gentamicin) Most effective against Gram-negative organisms. Associated with ototoxicity and nephrotoxicity; must be avoided in renal impairment.     * Macrolides: (e.g., Erythromycin, Clarithromycin) Erythromycin dose is $0.25-0.5\,g$ every $6\,hours$. Side effects include cholestatic jaundice and QT prolongation.     * Quinolones: (e.g., Ciprofloxacin) Act by inhibiting DNA gyrase and Topoisomerase IV. Side effects include tendonitis and photosensitivity.     * Linezolid: Effective against Gram-positive bacteria (including MRSA). Available in both oral and IV forms.     * Tetracyclines: (e.g., Doxycycline) Characterized by a four-ring structure, amphoteric nature, and ability to act as chelating agents.
• Antifungals:     * Fluconazole: A triazole antifungal (Pregnancy Category C). Antacids do not affect its absorption.     * Griseofulvin: Absorption increases with fatty food and acidic medium. It reduces the efficacy of oral contraceptives through enzyme induction and can cause a disulfiram-like reaction with alcohol.     * Terbinafine: Used for ringworm and fungal toe infections ("carpenter rash"). Requires liver function monitoring.     * Amphotericin B: A parenteral (IV) antifungal.
• Antivirals:     * Acyclovir: Active against HSV and Varicella-Zoster, but inactive against Vaccinia virus. Requires renal dose adjustment.     * Ganciclovir/Valganciclovir: Commonly cause neutropenia.

Pharmaceutics and Compounding

• Formulation Components:     * Surfactants:         * Anionic: Sodium Lauryl Sulfate, Oleic Acid (used as detergents/foaming agents).         * Cationic: Cetrimide, Benzalkonium Chloride (used as antiseptics/disinfectants).     * Antioxidants: Butylated Hydroxyanisole (BHA).     * Chelating Agents: EDTA.     * Lubricants: Magnesium Stearate.     * Humectants: Urea (used in topical preparations to retain moisture).
• Sterility and Isotonicity:     * Sterility is essential for IV injections, ophthalmic solutions, and infusions, but NOT for enemas.     * Isotonicity is determined by freezing point depression or osmotic pressure. It is vital for SC injections, vaginal preparations, nasal, and ophthalmic solutions.     * Buffers are essential in vaginal preparations to maintain physiological pH.
• Tablet Quality and Testing:     * Official Tests: Dissolution, Disintegration, Content Uniformity, Friability.     * Hardness: Not an official pharmacopoeial test.     * Friability: Measures resistance to abrasion. Excess weight loss indicates poor quality.     * Capping: A defect where the upper or lower part of the tablet separates horizontally.     * Wax Matrix Core: Used for preparing extended-release tablets (e.g., Potassium Chloride).
• Storage and Handling:     * Monoclonal Antibodies (e.g., Efalizumab) must be stored at $2-8^{\circ}C$.     * High vapor pressure drugs or hygroscopic drugs require tightly closed containers.     * Topical patches should avoid sunlight and external heat sources (which can cause excessively rapid drug release).

Pharmacokinetics and Calculations

• Key Concepts:     * Steady State ($C_{ss}$): Reached after approximately $4-5$ half-lives ($95\%$). In constant IV infusion, $C_{ss}$ depends on the dosing rate and clearance ($Cl$).     * Volume of Distribution ($V_d$): Increases if plasma protein binding decreases (more free drug to distribute).     * Clearance ($Cl$): Relates to drug elimination. It is NOT determined by half-life alone; half-life depends on both $Cl$ and $V_d$.     * Ion Trapping: Basic drugs accumulate in acidic compartments, and acidic drugs accumulate in basic compartments. Alkalinizing urine increases the excretion of weak acids (e.g., using sodium bicarbonate for aspirin toxicity).     * First-Order Kinetics: Elimination rate is proportional to drug concentration. A linear decrease occurs when plotted on a log scale. After $5$ half-lives, $1/32$ ($3.125\%$) of the drug remains.
• Mathematical Formulas and Calculations:     * Molarity ($M$): $M = \frac{\text{moles}}{\text{Volume (L)}}$.         * Calculation for $100\,mL$ of $1M\,NaCl\,(\text{MW } 58.5)$: $\text{Moles} = 1 \times 0.1 = 0.1\,mol$. $\text{Mass} = 0.1 \times 58.5 = 5.85\,g$.     * Milliequivalents ($mEq$): $mEq = \frac{\text{mg} \times \text{valence}}{\text{MW}}$.         * Calculation for $92\,mg\,Na\,(\text{MW } 23, \text{ valence } 1)$: $\frac{92 \times 1}{23} = 4\,mEq$.     * Percentage Dilution: $C_1 \times W_1 = C_2 \times W_2$.         * To make $150\,g$ of $5\%$) from $10\%$) stock: $10 \times W_1 = 5 \times 150 \Rightarrow W_1 = 75\,g$.     * Bioavailability ($F$): $F = F_{absorbed} \times (1 - E)$, where $E$ is the hepatic extraction ratio.         * If $F_{absorbed} = 0.6$ and $E = 0.7$: $F = 0.6 \times (1 - 0.7) = 0.18$ ($18\%$).     * Flow Rate: $\text{gtt/min} = \frac{\text{Volume (mL)} \times \text{Drop Factor}}{\text{Time (min)}}$.         * For $120\,mL$ over $30\,min$ with factor $10$: $\frac{120 \times 10}{30} = 40\,gtt/min$.

Endocrinology and Metabolism

• Thyroid Disorders:     * Hypothyroidism: Characterized by high TSH and low T4. Treated with Levothyroxine.     * Hyperthyroidism: Characterized by low TSH and high T4. Levothyroxine overdose causes tachycardia, diarrhea, and tremors.     * Drug Interactions: Amiodarone and Lithium both affect thyroid function. Amiodarone can cause both hypo- and hyperthyroidism.
• Diabetes Mellitus:     * SGLT2 Inhibitors: Known as "Gliflozins" (e.g., Empagliflozin, Dapagliflozin). They act on the Sodium-Glucose co-transporter in the kidney. Contraindicated in dehydration.     * Hypoglycemia: Insulin has the highest risk. Symptoms include sweating, tremors, and palpitations. Diarrhea and hypertension are NOT symptoms.
• Corticosteroids:     * Secreted from the Adrenal Cortex; secretion is controlled by ACTH.     * Cushing Syndrome: Result of high cortisol (long-term glucocorticoid use). Symptoms include "moon face," weight gain, and hyperglycemia.     * Addison Disease: Result of low cortisol (adrenal insufficiency).     * Specific Drugs: Fludrocortisone is a mineralocorticoid. Hydrocortisone IV dose for acute asthma is $100\,mg$ every $6\,hours$.
• Gout:     * Acute Attack: Colchicine dose is $1\,mg$ then $0.5\,mg$ after $1\,hour$ (Max $1.5\,mg$). NSAIDs are also used; paracetamol is NOT preferred.     * Prophylaxis: Allopurinol (Xanthine oxidase inhibitor) is used once the acute attack has subsided. Its active metabolite is Oxypurinol.

Drug Interactions and Contraindications

• Warfarin Interactions:     * Increase INR/Bleeding: Amiodarone, Metronidazole, Quinolones, Celecoxib, Tramadol.     * Decrease INR/Effect: Enzyme inducers like Phenytoin, Carbamazepine, Rifampicin.     * No Interaction: Allopurinol, Spironolactone, Famotidine.
• CYP450 System:     * Located in the Endoplasmic Reticulum (ER). Requires NADPH as a cofactor.     * Inhibitors (Increase drug levels): Clarithromycin, Erythromycin, Diltiazem, Grapefruit juice (affects Felodipine and Diltiazem but NOT Fluoxetine).     * Inducers (Decrease drug levels): Rifampicin, St. John's Wort.
• The "Triple Whammy": Combination of an ACE inhibitor (or ARB) + Diuretic + NSAID (e.g., Naproxen) leads to a high risk of acute kidney injury.
• Disulfiram-like Reaction: Occurs when Metronidazole or Griseofulvin is consumed with alcohol.
• St. John's Wort: Reduces the efficacy of oral contraceptives (COC) and increases the metabolism of many drugs except Rifampicin (with which it has no significant interaction).

Miscellaneous

• Anemias: Chronic Kidney Disease (CKD) typically causes normocytic normochromic anemia due to erythropoietin deficiency.
• Cancer Therapy:     * MOPP Regimen: (Mustargen, Oncovin, Procarbazine, Prednisone) Used for Hodgkin Lymphoma.     * Toxicity: Myelosuppression (WBC and platelet reduction) typically occurs $6-14$ days after treatment starts. Epistaxis (nosebleed) in chemo patients indicates thrombocytopenia.     * Daunorubicin: Notably associated with cardiotoxicity.     * Methotrexate: Dosed weekly ($7.5\,mg$). Toxicity (myelosuppression/hepatotoxicity) is increased by Trimethoprim and treated with Folinic acid (Leucovorin).
• Breastfeeding:     * Mastitis: Continue breastfeeding or use a pump; do not stop.     * Vaginal Thrush: Doxepin is generally discouraged; hygiene is key. Partners do not always need treatment unless symptomatic.
• Biochemistry:     * DNA: Strands are held together by hydrogen bonds between bases and phosphodiester bonds within the strand. RNA is converted to DNA by Reverse Transcriptase.     * Enzymes: CPK (Creatine Phosphokinase) is a marker for Myocardial Infarction. ALT is a marker for Liver disease.     * Nutrients: Thiamine (B1) is essential in alcohol withdrawal to prevent Wernicke-Korsakoff syndrome. Vitamin B6 (Pyridoxine) is supplemented with Isoniazid.