A 23-year-old woman presents to the emergency department with acute onset of shortness of breath, wheezing, and chest tightness. This is her 4th visit for these symptoms in the last 5 years. She tells you she recently ran out of her normal "controller" medication. Concerned for an asthma exacerbation, you begin therapy with a short-acting beta2-agonist. What is the expected cellular response to your therapy?

Gs protein coupled receptor activates adenylyl cyclase and increases intracellular cAMP

Gq protein coupled receptor activates phospholipase C and increases intracellular calcium

Gq protein coupled receptor activates adenylyl cyclase and increases intracellular cAMP

Gs protein coupled receptor activates phospholipase C and increases intracellular calcium

Gi protein coupled receptor inhibits adenylyl cyclase and decreases cAMP

A 53-year-old man presents to the office for a routine examination. The medical history is significant for diabetes mellitus, for which he is taking metformin. The medical records show blood pressure readings from three separate visits to fall in the 130–160 mm Hg range for systolic and 90–100 mm Hg range for diastolic. Prazosin is prescribed. Which of the following are effects of this drug?

Vasodilation, bladder sphincter relaxation

Vasodilation, decreased heart rate, bronchial constriction

Vasodilation, increased peristalsis, bronchial dilation

Vasoconstriction, bladder sphincter constriction, mydriasis

Vasoconstriction, increase in AV conduction rate, bronchial dilation

A 72-year-old male presents to his primary care physician complaining of increased urinary frequency and a weakened urinary stream. He has a history of gout, obesity, diabetes mellitus, and hyperlipidemia. He currently takes allopurinol, metformin, glyburide, and rosuvastatin. His temperature is 98.6°F (37°C), blood pressure is 130/85 mmHg, pulse is 90/min, and respirations are 18/min. Physical examination reveals an enlarged, non-tender prostate without nodules or masses. An ultrasound reveals a uniformly enlarged prostate that is 40mL in size. His physician starts him on a new medication. After taking the first dose, the patient experiences lightheadedness upon standing and has a syncopal event. Which of the following mechanisms of action is most consistent with the medication in question?

Alpha-1-adrenergic receptor antagonist

Dihydropyridine calcium channel blocker

Alpha-2-adrenergic receptor agonist

Non-selective alpha receptor antagonist

A 75-year-old male arrives by ambulance to the emergency room severely confused. His vitals are T 40 C, HR 120 bpm, BP 80/55 mmHg, RR 25. His wife explains that he injured himself about a week ago while cooking, and several days later his finger became infected, oozing with pus. He ignored her warning to see a doctor and even refused after he developed fever, chills, and severe fatigue yesterday. After being seen by the emergency physician, he was given antibiotics and IV fluids. Following initial resuscitation with IV fluids, he remains hypotensive. The ED physicians place a central venous catheter and begin infusing norepinephrine. Which of the following receptors are activated by norepinephrine?

Alpha 1, Alpha 2, Beta 1, Beta 2

A 58-year-old woman presents to her physician complaining of a headache in the occipital region for 1 week. Past medical history is significant for essential hypertension, managed with lifestyle modifications and 2 antihypertensives for the previous 6 months. Her blood pressure is 150/90 mm Hg. Neurological examination is normal. A third antihypertensive drug is added that acts as a selective α2 adrenergic receptor agonist. On follow-up, she reports that she does not have any symptoms and her blood pressure is 124/82 mm Hg. Which of the following mechanisms best explains the therapeutic effect of this new drug in this patient?

Decreased peripheral sympathetic outflow

Vasodilation of peripheral arteries

Vasodilation of peripheral arteries and peripheral veins

Negative inotropic effect on the heart

Vasodilation of peripheral veins

You have been asked to deliver a lecture to medical students about the effects of various body hormones and neurotransmitters on the metabolism of glucose. Which of the following statements best describes the effects of sympathetic stimulation on glucose metabolism?

Epinephrine increases liver glycogenolysis.

Norepinephrine causes increased glucose absorption within the intestines.

Without epinephrine, insulin cannot act on the liver.

Peripheral tissues require epinephrine to take up glucose.

Sympathetic stimulation to alpha receptors of the pancreas increases insulin release.

Adrenergic receptor subtypes for USMLE Step 3: High-Yield Pharmacology Lessons

Receptor Roundup - The A-B-Cs of Sympathetics

Receptor	G-Protein Family	Second Messenger	Key Effects
α1	Gq	↑ IP₃, DAG, Ca²⁺	Vasoconstriction (↑BP), pupillary dilation (mydriasis), urinary retention, glycogenolysis.
α2	Gi	↓ cAMP	↓ Sympathetic outflow (central), ↓ insulin release, ↓ aqueous humor production.
β1	Gs	↑ cAMP	↑ Heart rate (chronotropy), contractility (inotropy), & conduction (dromotropy); ↑ renin release.
β2	Gs	↑ cAMP	Bronchodilation, vasodilation (in skeletal muscle, liver; ↓BP), uterine relaxation (tocolysis).
β3	Gs	↑ cAMP	↑ Lipolysis, relaxation of the bladder detrusor muscle.

⭐ Exam Favorite: Remember the organ count: you have 1 heart (β1) and 2 lungs (β2). This is critical for predicting effects of agonists/antagonists. For example, stimulating β1 increases heart rate, while stimulating β2 relaxes the bronchioles.

Signaling Pathways - The G-Protein Cascade

📌 Mnemonic: QISS & QIQ (α₁=Gq, α₂=Gi, β₁=Gs, β₂=Gs) and (D₁=Gs, D₂=Gi)

Gs (β₁, β₂, D₁): Receptor binding → Gs activates Adenylyl Cyclase → ↑ cAMP → activates Protein Kinase A (PKA) → specific protein phosphorylation.
Gi (α₂, D₂): Receptor binding → Gi inhibits Adenylyl Cyclase → ↓ cAMP → ↓ PKA activation.
Gq (α₁): Receptor binding → Gq activates Phospholipase C (PLC) → cleaves PIP₂.
- IP₃ → ↑ intracellular Ca²⁺ from sarcoplasmic reticulum.
- DAG → activates Protein Kinase C (PKC).

⭐ PKA, activated by the Gs pathway (β receptors), has tissue-specific effects. In cardiac muscle (β₁), it phosphorylates Ca²⁺ channels, boosting influx and contractility. In smooth muscle (β₂), it phosphorylates myosin light-chain kinase, leading to relaxation and vasodilation.

Organ Effects - Location, Location, Location!

📌 Mnemonic: You have 1 heart (β1) and 2 lungs (β2).

Cardiovascular
- Heart (β1): ↑ Heart rate (chronotropy), ↑ contractility (inotropy), ↑ conduction.
- Blood Vessels:
  - α1: Potent vasoconstriction (skin, splanchnic) → ↑ Blood Pressure.
  - β2: Vasodilation (skeletal muscle, liver) → ↓ Blood Pressure.
Pulmonary (β2)
- Relaxation of bronchial smooth muscle → Bronchodilation.
Ocular
- α1: Mydriasis (pupil dilation).
- α2/β2: Regulate aqueous humor; α2 ↓ production, β2 ↑ production.
Metabolic & Endocrine
- β1: ↑ Renin release (kidney).
- β2: ↑ Glycogenolysis, ↑ glucagon release.
- α2: ↓ Insulin release.

⭐ Epinephrine has a biphasic effect on blood pressure: at low doses, β2-mediated vasodilation dominates (↓ diastolic BP), while at high doses, α1-mediated vasoconstriction dominates (↑ systolic & diastolic BP).

High-Yield Points - ⚡ Biggest Takeaways

α1 receptors, primarily on vascular smooth muscle, mediate vasoconstriction via the Gq pathway.

α2 receptors act as presynaptic autoreceptors, inhibiting norepinephrine release through the Gi pathway.

β1 receptors are concentrated in the heart, increasing heart rate and contractility via the Gs pathway.

β2 receptors, found in the lungs and skeletal muscle vasculature, cause bronchodilation and vasodilation (Gs pathway).

D1 receptors in the renal vasculature mediate vasodilation.

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