amlodipine (amlodipine, SUITAB / Amlodin OD Tablet)

Combined Calcium Channel Blocker And Angiotensin-Converting Enzyme Inhibitor Overdose.

Kahal Fares F, Guérard-Poirier Natasha N, Ji Cheng C, Gursahaney Ashvini A et al.

Combined overdoses of angiotensin-converting enzyme inhibitors and calcium channel blockers are rare but associated with more severe toxicity than either agent alone. A 48-year-old woman presented to the emergency department nine hours after intentionally ingesting 40 tablets of amlodipine (10 mg) and 40 tablets of ramipril (10 mg). On arrival, she was hypotensive and tachycardic. Initial management included fluids, intravenous calcium and insulin bolus followed by high-dose insulin euglycaemic therapy (HIET). Despite escalating vasopressor support, she developed mixed vasoplegic and cardiogenic shock complicated by acute kidney injury, fluid overload, respiratory failure and metabolic acidosis, necessitating intubation and continuous renal replacement therapy. Improvement in haemodynamics was only achieved by day 9. She was transferred from the intensive care unit (ICU) on day 20 with residual weakness from ICU-acquired myopathy and was ultimately discharged after 66 days, with a prolonged hospitalisation attributed to delirium and deconditioning. Severe combined angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) overdose may cause prolonged, refractory haemodynamic instability requiring extended high-dose insulin euglycaemic therapy (HIET), vasoactive support and fluid administration. Concentrated insulin, dextrose and vasopressor preparations may help mitigate fluid overload. Angiotensin II may be a potential treatment for refractory vasoplegia, although evidence and availability remain limited. Secondary complications can prolong recovery beyond the duration of drug toxicity. This case highlights the need for individualised, multidisciplinary management, early HIET, vasoactive support and fluid-sparing strategies in severe combined ACEI and CCB overdose. Management of severe combined calcium channel blocker and angiotensin-converting enzyme inhibitor overdose may require prolonged resuscitation with high-dose insulin euglycaemic therapy, vasoactive support and fluid administration. The cumulative fluid requirements of these therapies, combined with complications such as acute kidney injury, can contribute to severe fluid overload. The use of concentrated insulin, dextrose and vasopressor preparations may help limit the iatrogenic fluid accumulation.Clinicians should anticipate and proactively manage secondary complications, including acute kidney injury, volume overload, respiratory failure and infection, as these complications may independently prolong recovery beyond the expected duration of drug toxicity.Combined angiotensin-converting enzyme inhibitor and calcium channel blocker overdose lacks established management guidelines and requires individualised, multidisciplinary care based on clinical severity and response to therapy.

Association of metoprolol with temporal changes in SIRT1, oxidative stress, and inflammatory biomarkers.

Gupta Sandeep Kumar SK, Kalita Jayantee J, Pandey Prakash C PC, Mahajan Roopali R et al.

There is a paucity of studies on the effect of beta-blocker on sirtuins (SIRT1)-mediated inflammation and oxidative stress in ischemic stroke. We report the effect of metoprolol on the temporal kinetics of SIRT1-mediated oxidative stress markers [catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and reactive oxygen species (ROS)], proinflammatory cytokines (TNFα and IL1β), and their association with outcomes. This was a sub-analysis of our earlier study on effect of beta-blocker in acute stroke. Forty-eight patients within 3-days of ischemic stroke were included. Their demographic characteristics, risk factors for stroke, GCS/NIHSS score, hematological and biochemical parameters, electrocardiogram, echocardiography, and cranial-MRI findings were noted. SIRT1, TNFα, and IL1β mRNA fold-changes were measured by using real-time PCR, and GPx, CAT, MDA, and ROS were measured by using a spectrophotometer. These biomarkers were also measured in 59 healthy-controls. The outcome was defined at 1 and 3-months using the modified Rankin Scale. Twenty-eight patients received metoprolol, and 20 received amlodipine. There is a gradual reduction in TNFα, IL1β, ROS, and MDA and an increase in CAT level in both groups; however, more marked in the metoprolol group. On day 15, the metoprolol group had a comparable level of SIRT1, TNFα, IL1β, and CAT to those with the healthy controls. Metoprolol in acute ischemic stroke helps in upregulating SIRT1 and CAT and downregulating TNFα and IL1β; however, the overall p-value for treatment-by-time interaction was insignificant. The patients in the metoprolol group had a better outcome at 3-months. A large study is needed to confirm these findings.

Persistent systemic hypertension in a child with carbonic anhydrase II deficiency.

Arslan Bengü B, Polat Recep R, Çelakıl Mehtap M

Carbonic anhydrase II (CA II) deficiency is a rare autosomal recessive disorder classically characterized by osteopetrosis, renal tubular acidosis (RTA), and intracranial calcifications. We report a 10-year-old girl with genetically confirmed CA II deficiency who developed acute severe hypertension after previously documented normotension. Blood pressure reached 160/100 mmHg and was accompanied by headache, vomiting, and transient neurological symptoms requiring intravenous antihypertensive therapy. Hypertension persisted beyond the acute episode and was confirmed by ambulatory blood pressure monitoring (ABPM) despite treatment, requiring long-term antihypertensive therapy. Serial ABPM during follow-up subsequently demonstrated sustained blood pressure control, permitting stepwise dose reduction and eventual discontinuation of amlodipine approximately two years after presentation. Systemic hypertension has not previously been reported in CA II deficiency. This single-patient observation is hypothesis-generating and does not establish a causal relationship.

Amlodipine-associated Angioedema.

Lee Mikyung L ML, Delijani David D, Vittorio Timothy T, Lee David N DN et al.