Telmisartan (Micardis)

Drug Class

Mechanism of Action

• Causing vasoconstriction
• Stimulating aldosterone secretion
• Promoting sodium and water retention

Pharmacokinetics

• Goodman & Gilman's Pharmacological Basis of Therapeutics; Brenner and Rector's The Kidney

Dosing

• Starting dose: 40 mg once daily
• Usual dose: 40-80 mg once daily
• Onset of action: ~3 hours (dose-dependent)
• Duration: 24 hours; the drug's effect may persist up to 7 days after stopping
• The uniquely long half-life makes telmisartan one of the most effective ARBs for 24-hour BP control, including nocturnal blood pressure.

Indications

1. Hypertension - first-line treatment; once-daily dosing provides full 24-hour coverage
2. Cardiovascular risk reduction - the landmark ONTARGET trial showed telmisartan had similar efficacy to ramipril (an ACE inhibitor) in reducing cardiovascular events (MI, stroke, cardiovascular death) in high-risk vascular patients, with less angioedema
3. Diabetic nephropathy / kidney protection - the INNOVATION trial showed ARB-based regimens (including telmisartan) reduced progression from micro- to macroalbuminuria in type 2 diabetes
4. ACE inhibitor intolerance - preferred alternative when ACE inhibitors cause cough or angioedema
5. Antipsychotic-associated hypertension - Maudsley Prescribing Guidelines note specific evidence for telmisartan in this setting

Comparison with ACE Inhibitors (ONTARGET)

• Telmisartan = ramipril for cardiovascular and kidney outcomes in high-risk patients
• ARBs cause no cough (unlike ACE inhibitors) and rarely cause angioedema
• Both drug classes show similar efficacy in type 2 diabetic nephropathy
• Combination of ARB + ACE inhibitor is NOT recommended - increases adverse effects (hypotension, renal failure, hyperkalemia) without adding benefit

Adverse Effects (Class Effects)

Key Contraindications

• Pregnancy (Category D/X - absolute contraindication in 2nd and 3rd trimesters)
• Bilateral renal artery stenosis
• Concurrent use with aliskiren in patients with diabetes or renal impairment
• Combination with another RAAS blocker (ACE inhibitor or aliskiren)

Special Points

• Hepatic disease: Use with caution - telmisartan is cleared almost entirely by the liver/bile; hepatic insufficiency raises plasma levels
• Renal disease: No dose adjustment required, making it convenient in CKD patients
• Telmisartan is not dialyzable, so no supplement dose is needed after dialysis
• Among ARBs, azilsartan is superior to telmisartan for BP lowering at equivalent doses, but telmisartan's long half-life gives it an edge in nocturnal/early-morning BP control

Recent Evidence (2024-2026)

Management of Diabetic Ketoacidosis (DKA)

Diagnostic Criteria (ADA - Adults)

DKA Treatment Algorithm

1. Initial Assessment & Monitoring

• IV access, continuous cardiac monitoring (ICU/HDU admission)
• Hourly blood glucose, q2-4h electrolytes, VBG
• Catheterize if oliguria/no urine output
• Check for precipitating cause (infection, missed insulin, MI, etc.)
• Typical deficits: 5-10 L fluid, 5-10 mmol/kg sodium, up to 7 mmol/kg potassium

2. IV Fluid Resuscitation

• First choice: 0.9% Normal Saline (even if serum osmolality is high - NS is relatively hypotonic)
• Rate: 2-4 L in the first 2-4 hours in DKA
• Once glucose falls to <250 mg/dL, add 10% dextrose as a substrate for continued insulin infusion
• Alternate with 0.45% NS as guided by sodium levels
• Caution: Slow the rate in ischemic heart disease, heart failure, or renal impairment

Large volumes of 0.9% NS can cause hyperchloremic normal anion gap acidosis - this is expected and self-corrects over days as the kidneys restore bicarbonate. - Goldman-Cecil Medicine

3. Insulin Therapy

• Do NOT start insulin if K+ <3.5 mEq/L - correct potassium first to avoid fatal hypokalemia
• Once glucose falls to <250 mg/dL AND ketones <1.0 mmol/L, reduce insulin infusion to 0.05 units/kg/hour
• If patient was already on background long-acting insulin subcutaneously, continue it alongside IV insulin
• Transition to subcutaneous insulin: Once patient can eat. Overlap SC and IV insulin by 1-2 hours before stopping the infusion to prevent rebound ketosis

Blood glucose falls ~10% per hour; acidosis corrects more slowly. - Goodman & Gilman's

4. Potassium Replacement

5. Bicarbonate

• Generally NOT recommended - risks paradoxically worsening CNS pH, volume overload, hypernatremia, and rebound alkalosis
• Consider only if:
  • pH <7.0 (some guidelines use <7.1) AND
  • Patient not responding to insulin and fluids
• If given: 100 mmol NaHCO3 in 400 mL water + 20 mEq KCl over 2 hours

6. Phosphate & Magnesium

• Measure and monitor levels
• Routine IV replacement is not recommended
• Replace only if phosphate <1.0 mg/dL with profound muscle weakness or respiratory compromise

7. Identify & Treat the Precipitating Cause

• Infection (most common - pneumonia, UTI, cellulitis)
• Insulin omission/non-compliance
• Ischemia (MI, stroke)
• Intoxication
• Iatrogenic (steroids, SGLT2 inhibitors)
• Initial presentation of new T1DM

Note: Elevated WBC and amylase in DKA do NOT necessarily indicate infection or pancreatitis - these are often direct effects of metabolic acidosis. - Goldman-Cecil Medicine

8. Resolution Criteria

• Blood glucose <200-250 mg/dL
• Serum bicarbonate ≥15 mmol/L
• Venous pH >7.3
• Anion gap closed (<12)
• Serum/capillary beta-hydroxybutyrate <1.0 mmol/L

9. Complications to Watch For

Recent Evidence (2024-2026)

• A 2026 meta-analysis (PMID: 41208563) found that adding early subcutaneous basal insulin alongside IV insulin infusion in DKA management reduces time to DKA resolution and facilitates earlier transition off IV insulin without increasing hypoglycemia risk.
• A 2025 consensus report (PMID: 40032308) reviewing the 2024 ADA/EASD consensus on hyperglycemic crises highlights updated guidance on fixed-rate IV insulin, ketone monitoring using beta-hydroxybutyrate, and expanded SGLT2-inhibitor-associated euglycemic DKA recognition.