Anti Hypertensive drugs overdose

Anti Hypertensives basics and their common side effects with the prompt management.

1. Anti Hypertensive Drugs Overdose Dr. Runal Shah MEM PGY-1, KDAH, Mumbai.

2. Case scenario 64 year male, brought to ED, in confused state, by the neighbors, complaints being generalized weakness developing over past one week, loss of appetite, easy fatigability, increased urination. Past history s/o Hypertension on oral medication. ED workup – Na-126, K-2.8, Cl-90, Creat-1.45, Bicarbs-22, Lact-2 ECG –

3. Anti Hypertensive agents Diuretics Acetazolamide Thiazides Loop diuretics K+ sparing diuretics Sympatholytics Alpha-1 blockers Central Alpha-2 agonists Nor-Epinephrine release inhibitors ACE Inhibitors ARBs Vasodilators Arteriolar dilatation – Hydralazine, Minoxidil Arteriolar + Venous dilatation – Nitroprusside

4. Diuretics Toxidrome : Tachycardia Hypotension, Hypovolemia Electrolytes Abnormality Hypo / Hyperkalemia Hypo / Hypercalcemia Hypomagnesemia ECG changes – Wide QRS, Tall T, Prolong QTc, these changes precipitates to Arrhythmias (Tachydysrhythmias)

5. Diuretics contd.. Loss of Urinary Bicarb – resulting in Metabolic acidosis most commonly seen with Acetazolamide. Loop diuretics use can cause hypomagnesemia, hypocalcemia, Hypochloremic hpokalemic alkalosis, in liver deranged pt can lead to Hepatic encephalopathy, N number of drug reactions are encountered. Thiazides – Hypercalcemia, Hyperuricemia, Fatal/ non-fatal Hyponatremia K+ sparing – Hyperkalemia is the main side effect

6. Sympatholytics Toxidrome: Hypotension Bradycardia CNS depression Hemolytic anemia ( Idiosyncratic reaction to MethylDopa)

7. Sympatholytics contd.. Alpha-1 Blockers decreases Peripheral venous resistance (PVR) – Orthostatic hypotension as 1 st dose side effect (30-90 min after taking drug) Clonidine : Central Alpha-2 agonist + Mu-receptor agonist Toxidrome mimics like opioid overdose – Bradycardia, Hypotension, Miotic pupils, Somnolence, Hypothermia, Apnea(later)

8. Vasodilators Toxidrome: Hypotension Tachycardia Increased Myocardial Oxygen demand Lupus like syndrome ( Idiosyncratic to Hydralazine) Thiocyanate and Cyanide toxicity

9. Vasodilators contd.. Lupus like syndrome – Continuous treatment can cause Auto-antibody mediated Risk factors – high dose, female sex, slow actylators Symptoms - Arthralgia/ itis, fever, pericardial effusion Manage with Anti inflammatory agents Prompt discontinuation of Hydralazine is required Cyanide and Thiocyanate toxicity – On higher infusion rates of Nitroprusside >5 mcg/kg/min Sodium Thiosulfate to administer as antidote

10. ACE-I & ARBs Toxidrome: Hypotension Hyperkalemia Cough Angioedema ( Idiosyncratic )

11. Captopril induced Hypotension & reversal with Naloxone?!

12. Management Airway (Angioedema related airway compromise) Breathing Circulation – Hypotension & Tachycardia to manage with fluid boluses of 0.9NS Refractory cases – Phenylephrine iv (100-200mcg/min iv and then maintenance 40-60mcg/min ) ?Naloxone – limited role (evidence not sufficient) Angioedema – IV Methyl-Pred 125mg iv, Diphenhydramine 50mg iv, IM Epinephrine 0.3mg sc Supportive management Charcoal – if ingestion <1hr back..

13. Workup Blood Investigations – Electrolytes, Blood gas, Renal Profile Urine routine, urine electrolytes Screening 2D echo Imaging – CT/MRI ---------------------------------------------------------------------------------------- Refractory Hypotension despite IV fluids Angioedema with airway compromise Hypo-Hyperkalemia with ECG changes / arrhythmias Hyponatremia requiring prompt correction or symptomatic Disposition

14. Thank you.. Ref : clinicalkey.com, pubmed.gov, Goodman & Gilman’s Pharmacology, Tintinalli's 7/e