In this episode, we discuss the evidence, safety, and place in therapy of Journavx® (suzetrigine), a newly approved analgesic with a unique non-opioid mechanism of action and additional considerations for its use.

Key Concepts

1. Suzetrigine is a first in its class NaV1.8 sodium channel blocker approved for short-term (14 days or less) pain relief in adults with moderate-to-severe pain. Unlike opioids, suzetrigine is non-sedating and non-dependence forming.
2. Suzetrigine is taken as a whole pill without cutting, crushing, or chewing following a particular dosing schedule where the first dose is taken on an empty-stomach.
   The most common side effects of suzetrigine include pruritus, muscle spasms, increased CPK, rash, and transient (reversible) eGFR decrease.
3. Suzetrigine goes through CYP3A metabolism and therefore has significant interactions with CYP3A inducers and inhibitors. Use with strong inhibitors and moderate to strong inducers is not recommended. Dose reduction of suzetrigine is required if used with moderate inhibitors of CYP3A.
4. Although not formally adopted in a guideline recommendation, suzetrigine’s current place in therapy can be moderate-to-severe acute pain relief in adult patients after NSAIDs/APAP options are exhausted, but before or in place of opioid therapy.

References

• Bertoch T, D'Aunno D, McCoun J, et al. Suzetrigine, a Nonopioid Na V 1.8 Inhibitor for Treatment of Moderate-to-severe Acute Pain: Two Phase 3 Randomized Clinical Trials. Anesthesiology. 2025;142(6):1085-1099. doi:10.1097/ALN.0000000000005460

In this episode, we review the pharmacology, indications, adverse effects, monitoring, and unique drug characteristics of angiotensin receptor blockers (ARBs).

Key Concepts

1. ARBs are equally efficacious as ACE inhibitors when used for hypertension, heart failure with reduced ejection fraction (HFrEF), chronic kidney disease (CKD) with proteinuria, and post-MI care. Some limited evidence suggests that they might be better in reducing albuminuria in patients with diabetes. ARBs are generally better tolerated than ACEi due to a lower risk of angioedema and dry cough.
2. While most ARBs are comparable to each other, small differences exists regarding hepatic metabolism (CYP metabolism for losartan, telmisartan, and azilsartan), degree of blood pressure lowering (generally better with azilsartan, olmesartan, valsartan, and candesartan), and additional pharmacological effects (telmisartan with PPAR-Y agonism, losartan with uricosuric effect).
3. ARBs are contraindicated in pregnancy, those with bilateral renal artery stenosis, and those with previous angioedema to ARBs. The most common adverse effects include hypotension and hyperkalemia, but in rare cases acute renal impairment can also occur.
4. Baseline serum creatinine and potassium should be monitored in patients taking ARBs. After initiation or dose adjustment, blood pressure, serum creatinine, and potassium should be repeated in 1-2 weeks. Signs and symptoms of hypotension as well as angioedema should be monitored throughout the treatment period.

In this episode, we discuss the diagnosis and treatment of resistant hypertension, including a newer endothelin receptor antagonist (ERA) called aprocitentan (Tryvio®).

Key Concepts

1. The diagnosis of true resistant hypertension is based on requiring more than 3 antihypertensives (ACE inhibitor or ARB + calcium channel blocker + diuretic) to achieve goal BP, ruling out inaccurate BP readings, and ensuring patient adherence to their antihypertensive therapy.
2. Non-pharmacologic therapy (especially dietary sodium restriction), medication adherence, and lifestyle changes are critical to the treatment of resistant hypertension.
3. The preferred 4th line option for most patients with resistant hypertension is spironolactone.
4. After adding spironolactone, additional therapies are based on expert opinion and patient-specific factors. These additional therapies may include beta blockers, alpha-2 agonists, alpha-1 blockers, hydralazine, minoxidil, and aprocitentan.

References

• Carey RM, Calhoun DA, Bakris GL, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72(5):e53-e90. doi:10.1161/HYP.0000000000000084
• Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874-2071. doi:10.1097/HJH.0000000000003480