Pharmacology - Renal & Endocrine Systems Flashcards

Question 1

Loop Diuretics: Drug Names & Mechanism of Action

Accepted Answer

**Drugs:** Furosemide, Bumetanide, Torsemide, Ethacrynic acid.

**MOA:** Inhibits the $Na^+/K^+/2Cl^-$ cotransporter ($NKCC2$) in the thick ascending limb of the loop of Henle. Abolishes the corticomedullary osmotic gradient, preventing urine concentration.

Question 2

Loop Diuretics: Key Side Effects & Pearls

Accepted Answer

**Side Effects (OH HALE):**
- **O**totoxicity (especially with Ethacrynic acid)
- **H**ypokalemia & Metabolic Alkalosis
- **H**ypocalcemia (loops lose $Ca^{2+}$)
- **A**llergic reactions (sulfa drugs, except ethacrynic acid)
- **L**ow $Mg^{2+}$ (hypomagnesemia)
- **E**xcess uric acid (hyperuricemia/gout)

Question 3

Thiazide Diuretics: Mechanism of Action & Site of Action

Accepted Answer

**Drugs:** Hydrochlorothiazide, Chlorthalidone, Indapamide, Metolazone.

**MOA:** Inhibits the $Na^+/Cl^-$ cotransporter ($NCCT$) in the **early distal convoluted tubule (DCT)**, decreasing $Na^+$ and $Cl^-$ reabsorption.

Question 4

Thiazide Diuretics: Adverse Effects profile

Accepted Answer

**HyperGLUC:**
- **Hyper**glycemia
- **Hyper**lipidemia
- **Hyper**uricemia
- **Hyper**calcemia (thiazides save $Ca^{2+}$)

**Other:** Hypokalemic metabolic alkalosis, hyponatremia, sulfa allergy.

Question 5

Potassium-Sparing Diuretics: Two Subclasses & MOA

Accepted Answer

1. **Aldosterone Receptor Antagonists:** Spironolactone, Eplerenone. Directly block aldosterone receptors in cortical collecting duct cells.
2. **ENaC Blockers:** Amiloride, Triamterene. Directly block Epithelial $Na^+$ Channels ($ENaC$) in the cortical collecting duct.

**Clinical Effect:** Prevents $K^+$ and $H^+$ excretion while causing mild natriuresis.

Question 6

Carbonic Anhydrase Inhibitors: MOA & Clinical Uses

Accepted Answer

**Drug:** Acetazolamide.

**MOA:** Inhibits carbonic anhydrase in the **proximal convoluted tubule (PCT)**, blocking $HCO_3^-$ reabsorption and $Na^+$ transport.

**Indications:** Glaucoma, idiopathic intracranial hypertension, acute mountain sickness, metabolic alkalosis.

Question 7

Osmotic Diuretics: Mannitol

Accepted Answer

**MOA:** Expands extracellular volume and increases tubular fluid osmolarity, causing water retention in the PCT and descending limb of Henle.

**Indications:** Increased intracranial pressure (cerebral edema), intraocular pressure (glaucoma).

**Contraindications:** Anuria, severe heart failure / pulmonary edema.

Question 8

Insulin Therapy: Classification by Action Duration

Accepted Answer

- **Rapid-acting:** Lispro, Aspart, Glulisine (15 min onset; postprandial control).
- **Short-acting:** Regular insulin (30 min onset; IV for DKA).
- **Intermediate-acting:** NPH (2-4 hr onset).
- **Long-acting (Basal):** Detemir, Glargine, Degludec (peakless; provides 24 hr baseline).

Question 9

Metformin (Biguanide): Mechanism of Action & Adverse Effects

Accepted Answer

**MOA:** Activates AMP-activated protein kinase (AMPK) $\rightarrow$ suppresses hepatic gluconeogenesis and increases peripheral insulin sensitivity.

**Adverse Effects:** GI distress (diarrhea, cramps), $B_{12}$ deficiency, **Lactic Acidosis** (rare, but severe; hold prior to IV contrast media and in severe renal dysfunction).

Question 10

Sulfonylureas: Mechanism of Action & Common Drugs

Accepted Answer

**Drugs:** 1st Gen: Chlorpropamide, Tolbutamide; 2nd Gen: Glipizide, Glyburide, Glimepiride.

**MOA:** Inhibits $K_{ATP}^+$ channels on pancreatic $\beta$-cells $\rightarrow$ cell depolarization $\rightarrow$ $Ca^{2+}$ influx $\rightarrow$ endogenous insulin exocytosis.

**Adverse Effects:** **Hypoglycemia** (highest risk in elderly/renal failure) and **weight gain**.

Question 11

SGLT2 Inhibitors (-gliflozins): MOA & Unique Toxicities

Accepted Answer

**Drugs:** Empagliflozin, Dapagliflozin, Canagliflozin.

**MOA:** Inhibits sodium-glucose cotransporter 2 ($SGLT2$) in the PCT $\rightarrow$ blocks glucose reabsorption $\rightarrow$ glucosuria.

**Side Effects:** Genital mycotic infections, urinary tract infections (UTIs), osmotic diuresis/hypotension, **euglycemic DKA**.

Question 12

GLP-1 Receptor Agonists (-tides): Mechanism & Benefits

Accepted Answer

**Drugs:** Liraglutide, Semaglutide, Exenatide.

**MOA:** Mimics incretin hormone GLP-1 $\rightarrow$ increases glucose-dependent insulin release, decreases glucagon secretion, delays gastric emptying.

**Clinical Benefits:** Promotes significant **weight loss** and cardiorenal protection.

**Risk:** Pancreatitis, thyroid C-cell tumor risk (in rodents).

Question 13

DPP-4 Inhibitors (-gliptins): Mechanism of Action

Accepted Answer

**Drugs:** Sitagliptin, Saxagliptin, Linagliptin.

**MOA:** Inhibits dipeptidyl peptidase-4 ($DPP-4$) enzyme $\rightarrow$ prevents degradation of endogenous incretins ($GLP-1$ and $GIP$).

**Key Characteristics:** Weight-neutral, low risk of hypoglycemia, minimal GI side effects.

Question 14

Thiazolidinediones (TZDs / -glitazones): MOA & Risks

Accepted Answer

**Drugs:** Pioglitazone, Rosiglitazone.

**MOA:** Agonist at $PPAR-\gamma$ (peroxisome proliferator-activated receptor gamma) $\rightarrow$ upregulates GLUT4 and adiponectin $\rightarrow$ increases peripheral insulin sensitivity.

**Risks/Adverse Effects:** Weight gain, fluid retention/edema, **contraindicated in NYHA Class III/IV Heart Failure**, increased fracture risk.

Question 15

Levothyroxine: Indication, MOA & Monitoring

Accepted Answer

**Indication:** First-line therapy for hypothyroidism and TSH suppression post-thyroidectomy.

**MOA:** Synthetic form of thyroxine ($T_4$), converted intracellularly to active triiodothyronine ($T_3$).

**Monitoring:** Serum **TSH level** (checked 6–8 weeks after dose adjustment due to long half-life of ~7 days).

Question 16

Antithyroid Drugs: Propylthiouracil (PTU) vs. Methimazole

Accepted Answer

**Both:** Inhibit thyroid peroxidase ($TPO$), blocking organification and coupling of iodine.

**PTU Specifics:** Also blocks peripheral $T_4 \rightarrow T_3$ conversion by 5'-deiodinase. Used in **1st trimester of pregnancy** and **thyroid storm**.

**Methimazole:** Preferred in **2nd & 3rd trimesters** due to lower risk of severe hepatotoxicity.

Question 17

Antithyroid Drugs: Shared Severe Adverse Effect

Accepted Answer

**Agranulocytosis:** A sudden, life-threatening drop in granulocytes ($ANC < 500/\mu L$).

**Clinical Management:** Patients presenting with fever, sore throat, or stomatitis must immediately stop the drug and obtain a complete blood count (CBC) with differential.

Question 18

Glucocorticoids: Mechanism of Anti-inflammatory Action

Accepted Answer

**Drugs:** Prednisone, Dexamethasone, Hydrocortisone, Methylprednisolone.

**MOA:** Binds intracellular glucocorticoid receptors $\rightarrow$ inhibits $NF-\kappa B$ transcription factor $\rightarrow$ decreases production of pro-inflammatory cytokines ($IL-2, TNF-\alpha$) and phospholipase $A_2$ (via lipocortin induction).

Question 19

Systemic Corticosteroids: Long-Term Adverse Effects

Accepted Answer

**Cushingoid Manifestations:**
- Hyperglycemia / steroid-induced diabetes
- Central obesity, moon facies, buffalo hump
- Osteoporosis & avascular necrosis of femoral head
- Skin thinning, striae, impaired wound healing
- Adrenal cortical atrophy (via HPA axis feedback suppression)

Question 20

Fludrocortisone: Profile & Primary Indication

Accepted Answer

**Class:** Synthetic mineralocorticoid with high mineralocorticoid-to-glucocorticoid potency ratio.

**MOA:** Mimics aldosterone by activating mineralocorticoid receptors in renal distal tubule $\rightarrow$ increases $Na^+$ reabsorption and $K^+/H^+$ excretion.

**Indication:** Replacement therapy in **primary adrenal insufficiency (Addison's disease)**.

Question 21

Desmopressin (DDAVP): Indications & Mechanism

Accepted Answer

**MOA:** Selective agonist for $V_2$ vasopressin receptors in the cortical collecting duct $\rightarrow$ increases cAMP $\rightarrow$ translocates Aquaporin-2 channels to the luminal membrane.

**Indications:** Central Diabetes Insipidus, nocturnal enuresis, von Willebrand Disease (stimulates release of vWF/Factor VIII from endothelial cells).

Question 22

Vasopressin Receptor Antagonists (-vaptans)

Accepted Answer

**Drugs:** Conivaptan ($V_1A / V_2$ blocker), Tolvaptan ($V_2$ selective blocker).

**MOA:** Blocks $V_2$ receptors in collecting tubules $\rightarrow$ promotes aquaresis (free water clearance without solute loss).

**Indication:** Syndrome of Inappropriate Antidiuretic Hormone ($SIADH$), hypervolemic or euvolemic hyponatremia.

Pharmacology - Renal & Endocrine Systems

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