Para-Clinical Pharmacology Flashcards

24 sample cards from the Pharmacology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. Why must a nitrate-free interval be maintained, and what drug interaction is dangerous with nitrates?

   Continuous nitrate exposure causes tolerance (depletion of sulfhydryl groups), so a daily nitrate-free interval of 8-12 hours preserves efficacy. Combining nitrates with PDE-5 inhibitors (sildenafil) causes profound, potentially fatal hypotension and is contraindicated.

2. Compare the three classes of antianginal drugs by how they reduce myocardial oxygen demand.

   Nitrates reduce preload (venodilation). Beta-blockers reduce heart rate, contractility, and BP, lowering demand and prolonging diastolic coronary perfusion. Calcium channel blockers reduce afterload (vasodilation) and, for non-dihydropyridines, heart rate and contractility.

3. State the Vaughan Williams classification of antiarrhythmic drugs with the target of each class.

   Class I: sodium channel blockers (Ia quinidine, Ib lidocaine, Ic flecainide). Class II: beta-blockers. Class III: potassium channel blockers (amiodarone, sotalol). Class IV: non-dihydropyridine calcium channel blockers (verapamil, diltiazem). Adenosine and digoxin are unclassified.

4. Contrast Class Ib and Class Ic sodium channel blockers by their effect on the action potential and typical use.

   Class Ib (lidocaine) has fast dissociation, shortens action potential duration, minimally affects QRS, and targets ventricular arrhythmias (especially ischemic). Class Ic (flecainide) has slow dissociation, markedly slows conduction (widens QRS), no change in APD, and is used for supraventricular arrhythmias but is proarrhythmic post-MI.

5. List the major organ toxicities associated with amiodarone.

   Amiodarone can cause pulmonary fibrosis, thyroid dysfunction (both hypo- and hyperthyroidism due to iodine content), hepatotoxicity, corneal microdeposits, blue-gray skin discoloration, and photosensitivity. It requires baseline and periodic pulmonary, thyroid, and liver monitoring.

6. Which drug classes reduce mortality in chronic heart failure with reduced ejection fraction (HFrEF)?

   ACE inhibitors/ARBs (or ARNI—sacubitril/valsartan), beta-blockers (carvedilol, metoprolol succinate, bisoprolol), mineralocorticoid receptor antagonists (spironolactone/eplerenone), and SGLT2 inhibitors reduce mortality. Diuretics and digoxin relieve symptoms but do not improve survival.

7. Describe the mechanism of action of digoxin in heart failure.

   Digoxin inhibits the $\ce{Na+/K+}$-ATPase, raising intracellular $\ce{Na+}$, which reduces $\ce{Na+/Ca^2+}$ exchange and increases intracellular $\ce{Ca^2+}$, producing a positive inotropic effect. It also increases vagal tone, slowing AV conduction (rate control in atrial fibrillation).

8. What factors predispose to digoxin toxicity, and what are its features?

   Hypokalemia (competes at the same ATPase site), hypomagnesemia, hypercalcemia, and renal impairment predispose to toxicity. Features include nausea/vomiting, visual disturbances (yellow-green halos), confusion, and arrhythmias. Severe toxicity is treated with digoxin-specific antibody fragments (Digibind).

9. Explain the mechanism of benzodiazepines versus barbiturates at the $GABA_A$ receptor.

   Both enhance $GABA_A$ chloride channel activity. Benzodiazepines increase the frequency of channel opening (require GABA present), giving a ceiling effect and greater safety. Barbiturates increase the duration of opening and at high doses directly open the channel, causing fatal respiratory depression with a low safety margin.

10. What is the antidote for benzodiazepine overdose, and what is a risk of its use?

    Flumazenil, a competitive $GABA_A$ benzodiazepine-site antagonist, reverses benzodiazepine sedation. Risk: it can precipitate seizures in benzodiazepine-dependent patients or in mixed overdoses (e.g., with tricyclic antidepressants).

11. Classify antidepressants into their main groups with an example and shared mechanism theme.

    SSRIs (fluoxetine)—block serotonin reuptake; SNRIs (venlafaxine)—block serotonin and norepinephrine reuptake; TCAs (amitriptyline)—block both plus muscarinic/H1/alpha effects; MAOIs (phenelzine)—inhibit monoamine oxidase; atypical (bupropion, mirtazapine). All ultimately increase synaptic monoamine availability; onset of benefit takes 2-4 weeks.

12. What is serotonin syndrome and its classic triad?

    Serotonin syndrome is excess serotonergic activity (e.g., SSRI plus MAOI, or SSRI plus tramadol). Classic triad: neuromuscular abnormalities (clonus, hyperreflexia, rigidity), autonomic instability (hyperthermia, tachycardia), and altered mental status. Management is drug withdrawal, supportive care, and cyproheptadine.

13. Why must tyramine-rich foods be avoided with MAO inhibitors?

    MAO normally degrades dietary tyramine. With MAOIs, tyramine accumulates and enters adrenergic nerves, displacing large amounts of stored norepinephrine, causing a hypertensive crisis ('cheese reaction'). Aged cheeses, cured meats, and fermented foods must be avoided.

14. Contrast the receptor profile and side effects of typical versus atypical antipsychotics.

    Typical antipsychotics (haloperidol, chlorpromazine) block $D_2$ receptors strongly, giving high extrapyramidal symptoms (EPS) and hyperprolactinemia. Atypicals (risperidone, olanzapine, clozapine) block $D_2$ plus $5-HT_{2A}$, causing fewer EPS but more metabolic effects (weight gain, diabetes, dyslipidemia).

15. List the extrapyramidal symptoms of antipsychotics in their typical order of onset.

    Acute dystonia (hours to days), akathisia (days to weeks), parkinsonism (weeks to months), and tardive dyskinesia (months to years, often irreversible). Neuroleptic malignant syndrome (rigidity, hyperthermia, autonomic instability, elevated CK) is a separate, life-threatening reaction.

16. What unique benefit and unique risk are associated with clozapine?

    Clozapine is uniquely effective for treatment-resistant schizophrenia and reduces suicidality. Its major risk is agranulocytosis, requiring regular white cell count monitoring; it also lowers the seizure threshold and can cause myocarditis.

17. Match these antiepileptic drugs to their principal mechanisms: phenytoin, valproate, ethosuximide, benzodiazepines.

    Phenytoin blocks voltage-gated $\ce{Na+}$ channels (use-dependent). Valproate blocks $\ce{Na+}$ channels, enhances GABA, and blocks T-type $\ce{Ca^2+}$ channels (broad spectrum). Ethosuximide blocks T-type $\ce{Ca^2+}$ channels (absence seizures). Benzodiazepines enhance $GABA_A$ (status epilepticus).

18. Which antiepileptic is first-line for status epilepticus and which for absence seizures?

    Status epilepticus: intravenous benzodiazepine (lorazepam or diazepam) first, followed by a longer-acting agent such as phenytoin/fosphenytoin or levetiracetam. Absence seizures: ethosuximide (or valproate if generalized tonic-clonic seizures coexist).

19. Why is phenytoin difficult to dose, and what is its kinetic hallmark?

    Phenytoin exhibits zero-order (saturable) kinetics at therapeutic doses, so small dose increases can cause disproportionate rises in plasma concentration and toxicity (nystagmus, ataxia, gum hyperplasia). It also has a narrow therapeutic range and is a strong CYP450 inducer.

20. Differentiate the mechanisms of NSAIDs and opioids as analgesics.

    NSAIDs inhibit cyclooxygenase (COX-1/COX-2), reducing prostaglandin synthesis and peripheral sensitization (anti-inflammatory, antipyretic). Opioids act as agonists at $\mu$, $\kappa$, and $\delta$ receptors (GPCRs), inhibiting ascending pain pathways and altering pain perception centrally.

21. Describe the classic triad of opioid overdose and its antidote.

    The triad is CNS depression (coma), respiratory depression, and pinpoint (miotic) pupils. The antidote is naloxone, a competitive opioid receptor antagonist; because it is short-acting, repeated doses or infusion may be needed to prevent re-sedation.

22. Classify oral antidiabetic drugs by mechanism with an example of each key class.

    Biguanides (metformin)—decrease hepatic gluconeogenesis, increase insulin sensitivity; sulfonylureas (glibenclamide)—close $\ce{K_{ATP}}$ channels to stimulate insulin release; thiazolidinediones (pioglitazone)—PPAR-$\gamma$ agonists improving sensitivity; DPP-4 inhibitors (sitagliptin) and GLP-1 agonists (liraglutide)—incretin pathway; SGLT2 inhibitors (empagliflozin)—increase urinary glucose excretion.

23. Why is metformin first-line for type 2 diabetes, and what is its most serious adverse effect?

    Metformin is first-line because it lowers glucose without causing hypoglycemia or weight gain, and has cardiovascular benefit. Its most serious (rare) adverse effect is lactic acidosis, so it is avoided in significant renal impairment, hypoxia, or severe hepatic disease.

24. Compare the mechanisms of carbimazole/methimazole and propylthiouracil in hyperthyroidism, and name the drug preferred in first-trimester pregnancy and thyroid storm.

    Both are thioamides that inhibit thyroid peroxidase, blocking iodination and coupling of thyroglobulin. Propylthiouracil additionally inhibits peripheral conversion of $T_4$ to $T_3$. Propylthiouracil is preferred in the first trimester of pregnancy (less teratogenic) and in thyroid storm; carbimazole/methimazole is preferred otherwise.

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