This document discusses angiotensin blockers and ACE inhibitors, their mechanisms and uses for treating hypertension, heart failure, and myocardial infarction. It also covers their potential adverse effects like hypotension, hyperkalemia, and angioedema. Treatment recommendations include IV fluids for hypotension and switching medications for angioedema. Guidance is provided for managing hyperkalemia and potential liver injury from these drugs.
This document discusses angiotensin blockers and ACE inhibitors, their mechanisms and uses for treating hypertension, heart failure, and myocardial infarction. It also covers their potential adverse effects like hypotension, hyperkalemia, and angioedema. Treatment recommendations include IV fluids for hypotension and switching medications for angioedema. Guidance is provided for managing hyperkalemia and potential liver injury from these drugs.
This document discusses angiotensin blockers and ACE inhibitors, their mechanisms and uses for treating hypertension, heart failure, and myocardial infarction. It also covers their potential adverse effects like hypotension, hyperkalemia, and angioedema. Treatment recommendations include IV fluids for hypotension and switching medications for angioedema. Guidance is provided for managing hyperkalemia and potential liver injury from these drugs.
This document discusses angiotensin blockers and ACE inhibitors, their mechanisms and uses for treating hypertension, heart failure, and myocardial infarction. It also covers their potential adverse effects like hypotension, hyperkalemia, and angioedema. Treatment recommendations include IV fluids for hypotension and switching medications for angioedema. Guidance is provided for managing hyperkalemia and potential liver injury from these drugs.
• The angiotensin-converting enzyme (ACE) inhibitors and
angiotensin receptor (AR) blockers are widely used for the treatment of patients with • Hypertension • Heart failure • Myocardial infarction. Mechanism of toxicity • ACE inhibitors reduce vasoconstriction and aldosterone activity by blocking the enzyme that converts angiotensin I to angiotensin II. AR blockers directly inhibit the action of angiotensin II. • Angioedema and cough associated with ACE inhibitors are mediated by bradykinin, which normally is broken down by angiotensin-converting enzyme.
• Rare cases of acute liver injury (hepatocellular and/or
cholestatic) have been associated with both ACE inhibitors and AR blockers, by unclear mechanisms. Clinical presentation
• Hypotension, bradycardia
Adverse effects reported at therapeutic doses
• Hyperkalemia
• Bradykinin-mediated effects (dry cough and angioedema)
Treatment • If hypotension occurs, treat it with supine positioning and IV fluids. Vasopressors are rarely necessary.
• Treat angioedema with usual measures (eg,
diphenhydramine, corticosteroids) and discontinue the ACE inhibitor. Switching to an AR blocker may not be appropriate as angioedema has also been reported with these agents. Treat hyperkalaemia if it occurs. A potassium level higher than 6 mEq/L is a medical emergency; a level higher than 7 mEq/L is critical. 1. Administer 10% calcium chloride or 10% calcium gluconate if there are signs of critical cardiac toxicity such as wide QRS complexes, absent P waves, and bradycardia. 2. Glucose plus insulin promotes intracellular movement of potassium 3. Inhaled beta2-adrenergic agonists such as albuterol also enhance potassium entry into cells. 4. Hemodialysis rapidly lowers serum potassium levels. 5. Sodium bicarbonate may drive potassium into cells and lower the serum level.
• Decontamination Administer activated charcoal orally if conditions are appropriate Antidiabetic drugs Mechanism of toxicity
1.Sulfonylureas Lower blood glucose primarily by stimulating endogenous pancreatic insulin secretion and secondarily by enhancing peripheral insulin receptor sensitivity and reducing glycogenolysis.
Sulfonylureas include: • First generation: tolbutamide, chlorpropamide.
• Second generation: glibenclamide (glyburide),
glimepiride, glipizide, gliclazide. 2. Meglitinides (Nateglinide, Repaglinide) Increase pancreatic insulin release in a manner similar to that of the sulfonylureas
3. Biguanides (Metformin) • Metformin acts by inhibiting gluconeogenesis and glycogen breakdown, decreasing glucose absorption and improving peripheral insulin sensitivity. Clinical presentation 1) Hypoglycemia Manifestations of hypoglycemia include Agitation, confusion, coma, seizures, tachycardia, and diaphoresis.
2) Serum potassium and magnesium levels may also be depressed.
Clinical presentation of Metformin poisoning • Nausea, vomiting, diarrhoea and abdominal pain (Most common) • Coma, seizures • Rapid, deep breathing • Hypotension, cardiac dysrhythmias • Lactic acidosis is common with serious intoxication and may be fatal. The risk increases in the presence of renal dysfunction. • Pancreatitis Treatment
• If the patient is hypoglycemic, administer concentrated glucose. In
adults, give 50% dextrose; in children, use 25% dextrose.
• Octreotide for treating refractory or recurrent hypoglycemia as a
result of sulfonylurea or meglitinide poisoning. Octreotide, a synthetic somatostatin analog that inhibits pancreatic insulin secretion.
• Lactic acidosis can be treated with sodium bicarbonate; however,
bicarbonate infusions alone are often ineffective and patients with severe acidosis may require hemodialysis. • Decontamination Administer activated charcoal orally if conditions are appropriate.
• Enhanced elimination Alkalinization of the urine increases the renal elimination of chlorpropamide. The high degree of protein binding of the sulfonylureas suggests that dialysis procedures would not generally be effective.
Hemodialysis is recommended for correction of severe acidosis and
also enhances the clearance of metformin . CNS stimulants Amphetamines • Dextroamphetamine and methylphenidate are used for the treatment of narcolepsy and for attention-deficit hyperactivity disorder (ADHD) in children.
• Several amphetamine-related drugs (benzphetamine, diethylpropion,
phendimetrazine, phenmetrazine, and phentermine) are marketed as prescription anorectic medications for use in weight reduction.
• Fenfluramine and dexfenfluramine were marketed as anorectic medications but
were withdrawn from the market in 1997 because of concerns about cardiopulmonary toxicity with long-term use. • Methamphetamine (“crank,” “speed”), 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”), paramethoxyamphetamine (PMA), and several other amphetamine derivatives are used as illicit stimulants and hallucinogens. Mechanism of toxicity • Amphetamine and related drugs induce CNS stimulation, mainly by causing release of catecholamines (epinephrine, norepinephrine, dopamine) into central synaptic spaces, inhibiting their reuptake into nerve endings, and inhibiting monoamine oxidase.
• Amphetamines, particularly MDMA, PMA, fenfluramine, and dexfenfluramine,
also cause serotonin release and block neuronal serotonin uptake. Clinical presentation Acute CNS effects of intoxication of amphetamines include • Euphoria
• Talkativeness
• Anorexia
• Agitation, psychosis, seizures
• Intracranial hemorrhage may occur owing to hypertension or cerebral vasculitis.
Acute peripheral manifestations include
• Sweating
• Tremor, muscle fasciculations and rigidity
• Tachycardia, hypertension, acute myocardial ischemia, and infarction (even with
normal coronary arteries) Death may be caused by • Ventricular arrhythmia • Status epilepticus • Intracranial hemorrhage, or • Hyperthermia.
Hyperthermia frequently results from seizures and muscular hyperactivity and may cause brain damage, rhabdomyolysis, and myoglobinuric renal failure. Treatment • Agitation: Benzodiazepines are usually satisfactory, although antipsychotic agents may be added as needed.
• Hypertension is usually controlled by sedatives alone and, if this is not effective, a
parenteral vasodilator such as phentolamine or nitroprusside are good adjuncts.
• Treat tachyarrhythmias with propranolol or esmolol.
Note: Paradoxical hypertension is postulated to occur due to unopposed alpha- adrenergic effects when beta2-mediated vasodilation is blocked; be prepared to give a vasodilator if needed. • Treat arterial vasospasm
Peripheral ischemia • IV nitroprusside or IV phentolamine. Nifedipine or other vasodilating calcium antagonists may also enhance peripheral blood flow. • Heparin
Coronary spasm • Nitroglycerin sublingually or IV. Intracoronary artery nitroglycerin may be required if there is no response to IV infusion. • Calcium antagonist • Decontamination Activated charcoal, gastric lavage
• Enhanced elimination Dialysis and hemoperfusion are not effective.
