Crafting Effective Multiple Choice Questions

Psychoactive Drugs

• Lithium: Used for treating manic-depressive illness (bipolar disorders) and preventing chronic cluster headaches.
• Inhibits the synthesis and release of thyroid hormones, leading to hypothyroidism.
• Cationic metal; does not bind to proteins.
• PO administration leads to rapid and complete absorption.
• Distribution is uniform throughout the body water; reabsorbed.
• Given with demeclocycline inhibits ADH action on kidneys.
• Therapeutic range: 0.8-1.2 mmol/L.
• Toxic levels: 1.2-2 mmol/L, symptoms include apathy, lethargy, speech difficulties, seizures, and coma. >2 mmol/L
• Elimination: Renal filtration.

Tricyclic Antidepressants (TCAs)

• Used to treat depression, insomnia, extreme apathy, and loss of libido.
• PO administration is variable; slow gastric emptying and intestinal motility.
• Highly protein-bound (85-95%).
• Examples: Imipramine, Amitriptyline, Doxepin, Nortriptyline, Trazodone.
• Elimination: Hepatic metabolism
• Peak Serum Concentration: 2-12 hours
• Therapeutic level: 100-300 ng/mL
• Toxic effects: Drowsiness, blurred vision, memory loss, seizure, cardiac arrhythmia, Parkinsonian syndrome, and unconsciousness.

Fluoxetine

• Blocks the re-uptake of serotonin in central serotonergic pathways.
• Used for treating obsessive-compulsive disorder (OCD)
• Therapeutic level: 90-300 ng/mL
• Toxic effects: Attempted suicide, decreased libido, and decreased sexual function.

Bronchodilator (Theophylline)

• Methylated xanthine.
• Relaxes bronchial smooth muscle.
• Inhibits histamine and other pro-inflammatory agents.
• Used in the treatment of asthma, and chronic obstructive pulmonary disease (COPD).
• Useful for primary apnea of prematurity (absence of respiratory effort in newborn infants).
• Administration: 1st IV, 2nd Orally, 50% protein bound, crosses the placenta.
• Toxicity prediction: Blood level of the drug.
• Elimination: Renal filtration and hepatic metabolism
• Therapeutic level: 10-20 µg/mL
• Toxic level: >20 µg/mL.
• Toxic effects: GI bleeding, seizures, tachycardia, and syncope.

Immunosuppressive Drugs

• Cyclosporine: Inhibits cellular immune response, useful for preventing rejection of allogenic organ transplants, utilized for suppression of acute graft-versus-host disease (GVHD).
• High dose (300 ng/mL) required for heart, liver, and pancreas
• Marked RBC affinity (temperature dependent).
• PO administration (5-50%).
• Elimination: Hepatic metabolism
• Best sample: Whole blood (with lysis of RBC).
• Toxic level: >500 ng/mL. Toxic effects: Renal tubular and glomerular dysfunctions, GI disturbances, hirsutism, and hematologic dyscrasia.
• Tacrolimus (FK-506): 100x more potent than cyclosporine, GIT uptake variable, levels increase in cholestasis
• Elimination: Hepatic metabolism; specimen of choice: whole blood
• Toxic effects: Thrombus formation, nephrotoxicity, and neurotoxicity.
• Rapamycin: Similar to tacrolimus, major side effects: lipid abnormalities, and thrombocytopenia.
• Mycophenolate mofetil: Decreases renal rejection, inhibits lymphocyte proliferation; used for treatment of rheumatoid arthritis
• Leflunomide (LFM): Inhibits lymphocyte proliferation, used for treatment of rheumatoid arthritis.

Antineoplastic Drugs

• Methotrexate: Effective therapy for various neoplastic conditions; immunosuppression.
• Inhibits DNA synthesis by blocking dihydrofolate reductase.
• Leucovorin is a rescue drug for methotrexate toxicity.
• Toxic level = 0.01 umol/L
• Toxic Effects: Leucopenia, GI Ulceration, Thrombocytopenia, and Cirrhosis
• Busulfan: Alkylating agent used before bone marrow transplantation for leukemias and lymphomas.
• Overdose leads to Hepatic Occlusive Disease

Anti-inflammatory/Analgesics

• Salicylates/Aspirin: Direct stimulator of the respiratory system; inhibitor of Krebs' Cycle.

• Antiplatelet effects.

• Decreases TXA and PG.

• Acute aspirin intoxication is a common cause of fatal drug poisoning in children.

• Side effects: GI disturbance, interference with platelet aggregation, toxic level >30mg/dL

• Methods: Trinder Assay, enzymatic assay (salicylate hydroxylase), EMIT, and HPLC for determining concentration

• Acetaminophen: Inhibits prostaglandin metabolism; analgesic and antipyretic; overdose leads to hepatotoxicity.

• Toxic doses cause acute liver injury, very high doses cause fulminant hepatic failure. Not evident until several days after ingestion.

• Severe poisoning: CNS stimulation followed by CNS depression, vascular collapse, shock, total seizure, and coma that may be preceded by death

• Chronic abuse results in chronic toxicity and death, anemia, and gastrointestinal disturbances

• Toxic Levels: 25 ug/mL, 100-300 ug/ml (hepatotoxicity)

• Ibuprofen: Analgesic/anti-inflammatory.

• Lower risk of toxicity than salicylates and acetaminophen.

• Toxic Effects: Nausea/Vomiting, blurred vision, abdominal pain, and edema

• Therapeutic level: 10-50 µg/mL

• Toxic level: >100 µg/mL

Neuroleptics (Antipsychotic Major Tranquilizers)

• Blocks dopamine and serotonin action in the limbic system.
• Used in the treatment of schizophrenia.
• Difficult to monitor due to abundant serum metabolites and extensive hepatic metabolism.
• Typical antipsychotics: Chlorpromazine, Haloperidol
• Atypical antipsychotics: Risperdal, Olanzapine, Quetiapine, Aripiprazole
• Toxic effects: Cholestasis, orthostatic hypotension, aplastic anemia, and muscle rigidity

Carbohydrates

• Glucose: The only carbohydrate directly used for energy or stored as glycogen; does not enter muscle tissue freely.
• Brain is completely dependent on blood glucose for energy; 2/3 glucose utilization occurs in the CNS.
• Reducing Sugars: Glucose, maltose, fructose, lactose, galactose
• Sucrose: Nonreducing sugar; does not contain an active ketone or aldehyde group.

Pancreas

• Endocrine Gland: Secretes insulin, glucagon, and somatostatin.
• Exocrine Gland: Secretes amylase for complex carbohydrate breakdown and digestion.
• Islet of Langerhans: Beta cells: Insulin, Amylin, Alpha cells: Glucagon, Delta Cells: Somatostatin, F Cells: Pancreatic polypeptide

Insulin

• Primary hormone responsible for glucose entry into the cell.
• Promotes glycogenesis, lipogenesis, and glycolysis.
• Suppresses glycogenolysis.

Glucagon

• Hyperglycemic agent.
• Released during stress and fasting.
• Enhances catabolic functions; promotes glycogenolysis.
• FP Glucagon = 25-50 pg/mL
• Additional Hormones that increase blood glucose:* Cortisol, Corticosteroids, Catecholamines, Growth Hormone, Thyroid Hormones, Adrenocorticotropic Hormone (ACTH), and Somatostatin

Clinical Conditions Related to Carbohydrate Metabolism

• Hyperglycemia: Causes - Stress, severe infection, dehydration, pregnancy, pancreatectomy, hemochromatosis, Insulin deficiency, Insulin receptor, FPG ≥126 mg/dL
• Hypoglycemia: Causes - Imbalance between glucose utilization and production; warning signs and symptoms related to CNS; Whipple’s Triad (low blood glucose levels).

Interpretation of Plasma Glucose Values

• 65-70 mg/dL: Glucagon and other glycemic hormones released into circulation.
• 50-55 mg/dL: Observable hypoglycemic symptoms appear.
• ≤50 mg/dL: Low value and potentially abnormal for infants (require further diagnostic tests); impairment of cerebral function starts.

Symptoms of Hypoglycemia

• Neurogenic: Tremors, palpitations, anxiety, and diaphoresis;
• Neuroglycopenic: Dizziness, tingling, blurred vision, confusion, and behavioral changes

Classification of Hypoglycemia

• Drug-induced, Critical illnesses, Hormonal deficiency, Endogenous hyperinsulinism, Autoimmune hypoglycemia, Non-beta cell tumors
• Hypoglycemia of infancy and childhood, and Alimentary (reactive) hypoglycemia

If Px is suspected of Endogenous Hyperinsulinism

• Plasma glucose
• Insulin and Proinsulin
• C-peptide
• Beta-hydroxybutyrate
• Insulin antibodies
• Oral hypoglycemic drugs

Clinical Hypoglycemia

• Plasma/serum glucose concentration is low enough to cause symptoms/signs of impairment of brain function.

Factitious Hypoglycemia

• Intentional attempt to induce low blood glucose levels (e.g., self-administration of insulin/insulin-secretagogues.)

Diabetes Mellitus (DM)

• Hyperglycemia due to defects in insulin secretion or insulin receptors.
• FPG ≥ 126 mg/dL

Glucosuria/Ketosis

• Glucosuria: Excessive glucose in urine; >180 mg/dL (normal renal function).
• Ketosis: Excessive synthesis of Acetyl-CoA, leading to ketone body formation; severe ketoacidosis in type 1 DM.

Laboratory Findings in DM

• Increased glucose in plasma and urine, increased urine specific gravity.
• Presence of ketones in serum and urine, metabolic acidosis in blood and urine.
• Electrolyte imbalance (low sodium, high potassium, low bicarbonate), and high serum osmolality.

Classification of DM

• Type 1 DM (T1DM), Type 2 DM (T2DM), Gestational Diabetes Mellitus (GDM), and Other types of DM (OTODM)

Type 1 DM

• Insulin-dependent diabetes mellitus (IDDM), Juvenile onset diabetes mellitus.
• Brittle Diabetes, Labile diabetes, Ketosis-prone diabetes.
• Results from cellular-mediated auto-immune destruction of beta-cells.
• T1DM has insulinopenia (absolute insulin deficiency); loss of pancreatic beta cells.
• Prone to ketoacidosis

Characteristics of Type 1 DM

• Other detectable auto-antibodies: Tyrosine phosphatase IA-2 and IA-2B. Zinc transporter 8 8 antibodies, Islet autoantibodies, Polyuria, Polydipsia, Rapid weight loss, Polyphagia, Hyperventilation, Confusion.
• Complications: Microvascular disorders, very low or undetectable endogenous serum insulin.

Latent Autoimmune Diabetes in Adulthood (LADA)

• Type 1a or 1.5 diabetes mellitus, slow immune-mediated DM.
• Slowly progressive form of insulin-dependent Type 1 DM (SPIDDM).
• Moderate hyperglycemia with gradual autoimmune destruction of pancreatic beta cells, common among adults; associated with adult-onset T1DM, and resistant to ketosis.
• Shares immunological features with T1DM and T2DM
• Predisposing Factors: Low birth weight, advanced age, and family history of autoimmune disease.
• Signs and Symptoms: Similar to T1DM, Nocturia, Visual impairment, and Fatigue.

Fulminant Type 1 Diabetes

• Formerly considered idiopathic Type 1 DM or Type 1b DM; strongly inherited; associated with the complete absence of B-cell auto-antibodies; characterized by remarkably rapid, complete B-cell destruction, aggressive progression of hyperglycemia, and ketoacidosis.

Type 2 DM

• Non-insulin dependent diabetes mellitus (NIDDM), Adult Type/maturity Onset Diabetes Mellitus (DM), Stable Diabetes, Keto-resistant Diabetes, Receptor-Deficient Diabetes Mellitus.
• Hyperglycemia due to insulin resistance and defective insulin secretion.
• Strong genetic predisposition, but not related to autoimmune diseases.
• Risk Factors: Obesity, sedentary lifestyle, polycystic ovarian syndrome, dyslipidemia, and hypertension.
• Risk factors also include: Family history, advanced age, lack of exercise, and GDM.
• Recommendation: Adults aged 45 and above should be screened for DM every 3 years.

Comparison between T1DM and T2DM

• Indicators: Pathogenesis (B-cell destruction vs. insulin resistance); incidence rate (5-10% vs. 90-95%); onset (any age, most common in childhood/teens vs. any age, advancing age); risk factors (genetic/autoimmune vs. genetic, obesity, lifestyle); C-peptide levels (decreased/undetectable vs. detectable); pre-diabetes (autoantibodies + vs. autoantibodies -); symptomatology (symptoms develop abruptly vs. symptoms develop gradually, sometimes asymptomatic); ketosis (common, poorly controlled vs. rare); medication (parenteral insulin vs. hypoglycemic medications).

Gestational Diabetes Mellitus (GDM)

• Impaired ability to metabolize carbohydrates due to insulin deficiency, metabolic, and hormonal factors.
• Occurs during pregnancy and often disappears after delivery (2nd to 3rd trimester).
• Screening and Diagnosis through 2-hour OGTT.
• Diagnostic Tests: One-step, Two-step methods
• Diagnostic Criteria: FBS ≥92 mg/dL, 1-hour sample = ≥180 mg/dL, and 2-hour sample = ≥153 mg/dL.
• Infants born to diabetic mothers are at an increased risk for respiratory distress syndrome, hypocalcemia, and hyperbilirubinemia. Evaluation 6-12 weeks post-partum . Fetal insulin secretion is stimulated in the neonate, but ceases abruptly after cord severance.

Other Types of DM

• DM due to Pancreatic Disorders (e.g., chronic pancreatitis, malignancy (pancreatic CA), pancreatectomy)
• DM related to Endocrine Disorders (e.g., Cushing's syndrome, Pheochromocytoma, Acromegaly, Aldosteronoma, Hyperthyroidism)
• DM caused by genetic syndromes (e.g., Down syndrome, Klinefelter's syndrome, Rabson-Mendengall syndrome, Leprechaunism, and Huntington's chorea)
• DM associated with other exocrine diseases (e.g., cystic fibrosis)
• DM due to viral infections, e.g., CMV and Rubella.
• Drug-induced or chemical induced DM: Drugs that cause B-cell dysfunction (e.g., Dilantin, Pentamidine), thiazides, and glucocorticoids, leading to impaired insulin action

Samples for Glucose Measurement

• Random Blood Sugar (RBS), Fasting Blood Sugar (FBS), Two-hour Post-Prandial Blood Sugar (2-HPPBS), Glucose Tolerance Test (GTT), Glycosylated Hemoglobin (HbA1c), Fructosamine, and 1,5-anhydroglucitol (1,5-AG).

Lipids and Lipoproteins

• Major Functions of Lipids: Primary sources of fuel; Provide stability to cell membranes; Sources of hormones.

• Major Lipids in Plasma: Phospholipids, cholesterol, triglycerides, fatty acids, fat-soluble vitamins (ADEK).

• Phospholipid: Most abundant lipid derived from phosphatidic acid; originates in the liver & intestine; produced by the conjugation of two FA & a phosphorylated glycerol to a glycerol structure; Reference value: 150-380 mg/dL

• Cholesterol (3-hydroxy-5,6-cholestene): Unsaturated steroid alcohol; synthesized in the liver & found on the surface layer of lipoproteins as well as in plasma; does not serve as fuel/energy; transport & excretion are promoted by estrogen; Reference Value: <200 mg/dL

• Cholesterol - Diagnostic significance: Evaluates the risk for atherosclerosis, myocardial, and coronary arterial occlusions; direct relationship with MI; diagnosis/management of lipoprotein disorders, monitoring the effectiveness of lifestyle and stress management

• Increased Cholesterol: Hyperlipoproteinemia types II, III, and IV, Biliary cirrhosis, Nephrotic syndrome, Poorly controlled Diabetes Mellitus (DM), Alcoholism, and Primary hypothyroidism.

• Decreased Cholesterol: Severe hepatocellular disease, malnutrition, severe burns, hyperthyroidism, and malabsorption syndrome

• Triglyceride/Triacylglycerol (Neutral Fat): Very hydrophobic and water-insoluble, main storage lipid in humans; used as a source of energy during fasting states and between meals; Low caloric intake = low TG levels; Function: when metabolized their fatty acids (FA) are released into cells and provides excellent insulation, breakdown is facilitated by epinephrine, cortisol, and lipoprotein lipase. Fasting requirement: 10-12 hours; Reference Range: <150 mg/dL (normal). Interpretation: 150-199 mg/dL(Borderline), 200-499 mg/dL(High), ≥500 mg/dL (Very High): acute and recurrent pancreatitis. Diagnostic Significance: Evaluates for atherosclerosis risk, used in the management of CAD

• Fatty Acids: Mostly constituents of phospholipids or TAG in plasma; most bound to albumin; Polyunsaturated FA & cis-monounsaturated FA are not associated with elevated serum LDL cholesterol and often not measured; reference range: 9-15 mg/dL; Function: very important source of energy, provide substance for converting to glucose

• Lipoproteins (LPPs): Large macromolecules of lipids with specialized proteins (apolipoproteins) to transport lipids; purpose: to transport TAG and cholesterol to sites of energy and storage (utilization); Cholesterol/TAG in plasma are not free-floating, they are bound to lipoproteins; Apolipoprotein: keeps the lipids in solution during blood circulation, aids in solubilization and transfer of LPPs from GIT to the liver, facilitates uptake of LPPs into cells, maintains structural integrity of LPP complex

• ApoA-l and ApoB: Considered differential factors of atherosclerotic disease. ApoA-II; relates to insulin resistance and increased body fat. ApoB: nonexchangeable apolipoprotein, predictor risk of artery disease. Both are found in VLDL and LDL and useful markers in assessing lipid profile.

• Major Lipoproteins: Chylomicron (CM), VLDL, HDL, LDL, IDL

• Minor Lipoproteins: Intermediate Density Lipoprotein (IDL), Lipoprotein (a)/Lp (a).

• Abnormal Lipoproteins: Lipoprotein X, Oxidized HDL; B-VLDL (Floating ẞ lipoprotein)

This quiz explores the best practices for creating multiple choice questions. Understand the significance of a clear stem, plausible options, and effective distractors. Improve your skills in writing questions that are fair and informative.