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HY points followed by a quiz at the end
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What are α and β receptors?
- Catecholamines are hormones produced by adrenal medulla – i.e., epinephrine, norepinephrine, and dopamine.
- α and β receptors are bound by catecholamines.
- They are known as adrenergic receptors because the adrenal medulla hormones bind them.
USMLE wants you to know which receptors the catecholamines bind to:
- Epinephrine agonizes: α1, α2, β1, β2.
- Norepinephrine agonizes: α1, α2, β1, but not β2.
- Dopamine agonizes: α1, α2, β1, β2, D1.
- At low-dose dopamine, D1 is bound most strongly (makes sense); as dose increases, β and α receptors are also bound.
- If the USMLE Q tells you dopamine is used to increase someone’s BP, choose α1 as the answer.
β1 receptors
Where are β1 receptors predominantly found?
- Cardiac muscle.
- Juxtaglomerular cells of the kidney.
What HY β1 agonists do I need to know for USMLE?
Dobutamine.
What’s the main effect of β1 agonism?
↑ chronotropy (heart rate), ↑ inotropy (contractility), ↑ oxygen demand on the heart.
- Dobutamine is classically used as “dobutamine-echo” for stress tests in patients who cannot do an exercise stress test. Dobutamine will increase the heart rate, therefore increasing oxygen demand, and then the cardiac function can be evaluated using a transthoracic echo.
Causes increased renin release from the kidney.
- 22M + runs 10 miles and is dehydrated; which of the following would be expected in this patient? –> answer = “increased sympathetic nerve stimulation at the kidney.” This is because we’d have upregulation of the renin-angiotensin system to help restore blood volume, so ↑ β1 agonism via sympathetic nerve stimulation at JG cells –> increased renin release.
What HY β1 blockers do I need to know for USMLE?
Beta-blocker discussion is a bit lengthy but very HY.
Beta 1-selective blockers: A BEAM of beta-blockers –> Atenolol Bisoprolol, Esmolol, Acebutolol, Metoprolol.
- If it starts with a letter before M in the alphabet and ends in -olol, it’s beta 1-selective.
Beta 1/2 non-selective blockers: everything else –> i.e., Propranolol, Pindolol, Timolol, Nebivolol.
Beta-blockers with mixed alpha-blocking effect (i.e., mostly block beta, but also block alpha to a lesser degree): labetalol, carvedilol.
- Beta-blockers end with -olol. If the ending is not -olol (as with labetalol + carvedilol), that’s how you can remember it’s mixed.
What HY things do I need to know about β1 blockers?
The four beta-blockers that decrease mortality in heart failure: metoprolol XR, bisoprolol, carvedilol, nebivolol.
- USMLE will only ever write “metoprolol.” But some cardiologists on the ward will freak the fuck out if you don’t specify “extended release” as the metoprolol formulation when discussing mortality reduction in heart failure. “Regular” metoprolol is used for atrial fibrillation.
Hierarchy for drugs in heart failure (simplified but HY for USMLE):
- Start with ACE inhibitor or an angiotensin II receptor blocker (ARB) to improve ejection fraction (normal is 55-70%).
- If the patient is fluid overloaded (i.e., peripheral edema or pulmonary edema), attempt to achieve euvolemia by adding furosemide (loop diuretic).
- If insufficient ejection fraction with the ACEi or ARB, add a beta-blocker (metoprolol XR, bisoprolol, carvedilol, or nebivolol).
- If insufficient ejection fraction with ACEi/ARB + beta-blocker, add spironolactone (aldosterone receptor antagonist).
- If insufficient ejection fraction, add the combination of hydralazine + nitrates. Only the combo decreases mortality in HF. It is especially efficacious in African Americans (tend to have stiffer vessels).
- If insufficient ejection fraction when already on ACEi/ARB + beta-blocker + spironolactone + hydralazine + nitrates, add digoxin.
- If pharmacologic therapy insufficient, use implantable device.
- 68M + shortness of breath on exertion + peripheral edema + JVD + echo shows EF of 35%; what drug should be initiated to improve EF? –> answer = ACEi or ARB; beta-blocker is the wrong answer on USMLE.
Metoprolol is used for rate control in atrial fibrillation.
- When treating AF, we need to address both blood viscosity and the actual AF arrhythmia.
- For blood thinning: if low 0-1 CHADS2 score, give aspirin; if 2+ CHADS2 score, give warfarin or NOAC. Variations of the score exist, but the hyper-simple CHADS2 always works for USMLE Qs. CHF; HTN; Age 75+; Diabetes; Hx of Stroke/TIA. The latter is worth is worth 2; the others are all worth 1. It’s to my observation students tend to forget the age (they always say 70 or 65).
- For the actual AF, do rate control before rhythm control. For rate control, use “regular” metoprolol (in contrast to metoprolol XR for HF).
- If contraindication to beta-blocker (discussed below), verapamil (non-dihydropyridine CCB) is frequently used.
- If rate control insufficient, go to rhythm control.
- Flecainide (type Ic Na channel blocker) is used if the patient has AF with no LVH, structural heart disease, or coronary artery disease.
- If patient has LVH, structural heart disease, or coronary artery disease, other anti-arrhythmics, e.g., amiodarone or dofetilide (type III K channel blockers) can be used.
HY contraindications to beta-blockers:
- Hx of depression (beta-blockers can cause depression).
- Diabetes –> epinephrine is responsible for symptoms of hypoglycemia; with beta-blockade, symptoms can be masked. Diabetics on beta-blockers require diligent monitoring.
- COPD.
- Asthma (can use beta 1-selective, but cannot use non-selective) –> should be noted that a Q on one of the 2CK psych forms has benzo as the answer for social phobia, over propranolol, in a patient with simple asthma, so for USMLE purposes, asthma period, equals no beta-blocker).
- 2nd or 3rd-degree heart block.
- Unstable heart failure resulting in hemodynamic instability.
- Peripheral vascular disease no longer a contraindication.
Propranolol has many HY uses for USMLE:
- Can be used to treat essential or idiopathic tremors.
- 22F + bilateral resting tremor + mom also has tremor + self-medicates with alcohol to decrease tremor; Tx? –> answer = propranolol.
- Essential tremor is a bilateral resting tremor; it’s autosomal dominant; patients frequently self-medicate with alcohol, which decreases tremor.
- Tachycardia in hyperthyroidism.
- Beta-blockade decreases the conversion of T4 to T3.
- Prophylaxis for esophageal varices bleeding.
- 59M + alcoholic + vomits copious bright red blood that requires banding; what could be given to help prevent future episodes? –> answer = “beta blockade” (propranolol) –> decreases portal blood flow and, therefore, pressure.
- Treatment is banding and sometimes octreotide. But prophylaxis for a bleed is propranolol.
- Hypertrophic obstructive cardiomyopathy (HOCM).
- 20F + 2/6 mid-systolic murmur in upper chest + murmur worsens with Valsalva; what could be given to this patient to reduce risk of death? –> answer = propranolol –> slows heart rate –> increases time for diastolic filling –> lessens chance of low preload state where the murmur (LV outflow tract obstruction) worsens.
- Akathisia secondary to anti-psychotic use.
- 39M + schizophrenia + started taking olanzapine a week ago + feels constantly restless; Tx? –> answer = propranolol.
- Social phobia.
- 29M + needs to speak in front of large audience in upcoming presentation for work; Tx? –> propranolol.
- 2CK psych form gives two near-identical Qs – one mentions Hx of asthma; the other doesn’t – if patient has asthma, use benzo instead of beta-blocker for social phobia.
- Atenolol can be used for stage fright instead of propranolol (both are correct).
- Migraine prophylaxis
- 40F + high BP after lifestyle modification + Hx of migraines; which new medication do we start? –> answer = “beta blockade” (propranolol). This is on one of the 2CK FM forms.
- Treatment for migraines is NSAIDs followed by -triptans; prophylaxis is beta-blocker.
- Cluster headache prophylaxis is verapamil; beta-blocker is the wrong answer for cluster (low-30s%-correct Q in Qbank IIRC).
Topical timolol can be used for glaucoma.
- Beta-blockade decreases aqueous humor production.
- USMLE just wants you to know that beta-blockade, in general, can be used for glaucoma and reduces aqueous humor production.
- Propranolol is not used for glaucoma.
Any other weird factoids about β1 receptors I should know?
- Lower yield, but rarely they will ask about G-proteins (if you want >260 on Step 1).
- β1 receptors are G-α-s G-proteins, which means that agonism causes ↑ cAMP and antagonism ↓ cAMP.
- 34M + long Hx of migraines + started on new drug for HTN; what’s the molecular effect of this agent? –> answer = ↓ cAMP (propranolol).
β2 receptors
Where are β2 receptors predominantly found?
- Bronchiole smooth muscle (cause dilation).
- Peripheral arterioles (cause dilation).
- Uterus (cause relaxation).
What HY β2 agonists do I need to know for USMLE?
Beta 2-selective agonists: Albuterol, Salmeterol, Ritodrine.
Beta 2 non-selective agonists: Terbutaline, Isoproterenol.
What’s the main effect of β2 agonism?
Dilates bronchioles.
- Albuterol is a short-acting beta 2 agonist (SABA) used as the initial Tx in asthma.
- Whereas with asthma, albuterol is always the first med, in COPD it is sometimes chosen as the first med. Ipratropium, a muscarinic receptor antagonist, can also be used first-line in COPD (answer on one of the 2CK IM forms).
- Salmeterol is a long-acting beta 2 agonist (LABA) used after inhaled fluticasone in outpatient asthma management.
- For a more detailed post on asthma management, see here.
- Epinephrine is used as the Tx for anaphylactic shock because the β2 agonism functions to open the lungs.
Dilates peripheral arterioles.
- Selective β2 agonists can decrease BP in theory, but are not used for this purpose.
- If epinephrine is administered alone, BP will go up. However BP will decrease with epinephrine if alpha 1 is blocked first.
- “What do you mean? That’s confusing.” I know. Chill the fuck out. I’ll explain:
- If we give epinephrine (which agonizes α1, α2, β1, and β2), the strong vasoconstrictive effect of α1 on arterioles overpowers the peripheral vasodilatory effect of β2, so BP goes up with epinephrine administration alone.
- That is: effect of α1 outpowers β2, where effect of constriction > dilation, so BP goes up.
- But if we first block alpha 1 with phentolamine, then give epinephrine, the effect on β2 is no longer countered by α1, so we get dilation and BP decreases.
- “But Michael, how does the USMLE actually assess that?”
- Scientist is running an animal model experiment. Drug X is given and BP goes up. He then performs the experiment a second time. In this case, Drug Y is administered before drug X. BP goes down slightly with Drug Y. It then decreases further with Drug X. What are Drug X and Y? –> Answers: Drug X = epinephrine. Drug Y = phentolamine.
Can be used for tocolysis (cause relaxation of the uterus).
- Tocolytic agents (i.e.., ritodrine) delay labor and buy the expectant mother time in certain delivery situations.
- Woman at 32 weeks gestation is in labor + steroids have not yet been administered for fetal lung maturity + a β2 agonist is given as a tocolytic; which of the following agents is best described here? –> answer = ritodrine.
What HY things do I need to know about β2 blockers?
- There’s no such thing as a “beta 2 blocker.” It’s more that: of the standard β1 blockers we use for a variety of reasons, some are non-selective and also antagonize β2 (e.g., propranolol). But we don’t use selective β2 antagonists in medicine.
- According to Wikipedia, butaxamine is a select β2 blocker, but its use is limited to experimental research rather than actual medicine.
- The effect on G-proteins is the same as β1 – i.e., β2 activates G-α-s G-proteins, which means that agonism causes ↑ cAMP and antagonism ↓ cAMP.
β3 receptors
- Yeah. Weird and esoteric. But you need to know there’s a drug called mirabegron, which is a β3 agonist used for urge incontinence.
- Classic Tx for urge incontinence (overactive detrusor muscle) is oxybutynin, a muscarinic receptor antagonist. But mirabegron has been showing up on students’ USMLEs and shelf exams as well.
- So I want you to say: “Treatment for urge incontinence is almost always oxybutynin, a muscarinic receptor antagonist. But mirabegron is a beta 3 agonist that is newer and now shows up on the USMLE.”
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