Respiratory Drugs and Their Functions

Respiratory Drugs Overview

• Respiratory drugs include Dextromethorphan, PPA (Phenylpropanolamine), Theophylline, and Anti-inflammatory Agents.

Dextromethorphan

• Common ingredient in over-the-counter cough and cold medicines; recognized as a non-addictive opioid.
• Primarily functions as an antitussive (cough suppressant); found in products like Nyquil and Robitussin DM.
• Effective oral absorption; onset of effects within 15-30 minutes, with a duration of action of 3-6 hours.
• Toxicity generally occurs when doses exceed 10 mg/kg; symptoms can range from mild (clumsiness, hallucinations) to severe (stupor, respiratory depression).
• Contraindicated in cases of emesis (vomiting).

PPA & Related Decongestants

• PPA used as a nasal decongestant and appetite suppressant; can cause hemorrhagic stroke.
• Phenylephrine, Ephedrine, and Pseudoephedrine are common decongestants with sympathomimetic properties.
• Toxicity risks increase significantly with overdose; may lead to hypertensive crisis, confusion, and arrhythmias.
• Treatment includes vasodilators for hypertension, beta-blockers for arrhythmias, and careful monitoring in case of AV block or bradycardia.
• Urinary acidification can aid in elimination of toxic substances.

Anticholinergic/Antimuscarinic Bronchodilators

• Useful for COPD management; they include Ipratropium and Tiotropium.
• Mechanism: Block muscarinic receptors, which prevents contraction of airway smooth muscle.
• Side effects include tachycardia, constipation, and dry mouth.

Anti-inflammatory Agents

• Mast Cell Stabilizers: Prevent degranulation of mast cells which would cause bronchoconstriction.

  • Examples: Cromolyn sodium and Nedocromil; often used for allergic conditions and exercise-induced asthma.
  • Side effects may include bronchospasm; pre-treatment with beta-agonists recommended.

• Lipoxygenase Inhibitor: Zileuton inhibits leukotriene synthesis, helpful in managing inflammation in asthma.

  • Side effects include hepatotoxicity; regular monitoring of liver enzymes (ALT) is necessary during use.

Rhabdomyolysis and Myoglobin Deposition

• Rapid breakdown of damaged skeletal muscle can lead to myoglobin deposition in the kidneys, potentially resulting in kidney damage.

Theophylline Overview

• Methylxanthine used primarily for asthma treatment, administered orally or via IV infusion (aminophylline) for conditions like bronchospasm and congestive heart failure.
• Commonly prescribed in sustained-release forms such as Theo-Dur and Theobid.

Clinical Presentation of Theophylline Toxicity

• Acute overdose symptoms include tremors, anxiety, tachycardia, and seizures when serum levels exceed 100 mg/L.
• Chronic intoxication manifests as vomiting, hypokalemia, hyperglycemia, and seizures at levels around 40-60 mg/L.
• Less common symptoms: hypophosphatemia, metabolic acidosis, and ventricular arrhythmias.

Mechanism of Toxicity

• High levels inhibit phosphodiesterase, increasing cyclic adenosine monophosphate (cAMP).
• Stimulates beta-adrenergic receptors specifically in the lungs.
• Acts as an adenosine receptor antagonist, promoting the release of endogenous catecholamines.

Treatment for Theophylline Toxicity

• Supportive emergency measures are essential for management.
• Low-dose propranolol (0.01-0.03 mg/kg IV) may counteract some cardiovascular effects.

Dextromethorphan Overview

• Found in many OTC cough and cold medications; an opioid derivative that lacks analgesic properties.
• Acts as an antitussive (cough suppressant) without addictive effects, commonly combined with antihistamines or decongestants.

Clinical Presentation of Dextromethorphan Toxicity

• Toxic symptoms appear when intake exceeds 10 mg/kg; mild intoxication can lead to clumsiness, ataxia, and hallucinations.
• Severe overdose may cause stupor, coma, respiratory depression (especially when combined with alcohol), and seizures from doses of 20-30 mg/kg.

Mechanism of Dextromethorphan Toxicity

• Antagonizes NMDA glutamate receptors, leading to altered mental status and psychoactive effects.
• Increases serotonin levels, potentially causing serotonin syndrome, particularly in patients on monoamine oxidase inhibitors (MAOIs).

Treatment for Dextromethorphan Toxicity

• Emergency measures including naloxone may be needed if there's suspicion of opioid intoxication, typically administering 0.4-2 mg IV with repeat doses as necessary.
• Activated charcoal can assist in decontamination for overdose situations.

Important Considerations

• Dextromethorphan has anticholinergic properties and is well-absorbed orally, with effects observed within 15-30 minutes and a duration of 3-6 hours.
• Pediatric dosing is considerably lower than adults, up to 30 mg/d for children aged 2-5 years.

Emesis and Phenylpropanolamine (PPA)

• PPA is an appetite suppressant linked to an increased risk of hemorrhagic stroke.
• Toxic doses can occur with 2-3 times the therapeutic dose for PPA, phenylephrine, and ephedrine.
• Pseudoephedrine toxicity symptoms may arise after 4-5 times the therapeutic dose.
• Common in nonprescription nasal decongestants and cold preparations, which often combine antihistamines and cough suppressants.

Mechanism of Action

• PPA and phenylephrine act as direct alpha-adrenergic agonists and have mild beta-adrenergic stimulation effects.
• PPA enhances norepinephrine release, contributing to its sympathomimetic activity.
• Ephedrine and pseudoephedrine exhibit both direct and indirect alpha- and beta-adrenergic activities, resulting in substantial beta-adrenergic stimulation compared to PPA or phenylephrine.

Clinical Presentation of Toxicity

• Major symptoms include:
  • Hypertension due to alpha1-mediated vasoconstriction
  • Headache and confusion
  • Seizures and intracranial hemorrhage
  • Bradycardia or AV block affecting electrical conduction in the heart
  • Possible myocardial infarction

Treatment of Toxicity

• Emergency and supportive measures are critical.
• For hypertension with diastolic pressure > 100-105 mmHg, use vasodilators like phentolamine or nitroprusside.
• Do not administer beta blockers without prior vasodilator treatment; position patients upright.
• For arrhythmias, propranolol or esmolol may be given, but avoid beta blockers in bradycardia associated with hypertension.
• Ipecac-induced emesis, activated charcoal, and cathartics are used for decontamination.
• Urinary acidification enhances elimination for PPA, ephedrine, and pseudoephedrine.

Dextromethorphan and NMDA Receptor Inhibition

• Dextromethorphan and its metabolite inhibit NMDA glutamate receptors, leading to altered mental status and psychoactive effects.
• Inhibition of serotonin reuptake can lead to serotonin syndrome, characterized by confusion, agitation, tachycardia, hypertension, and mydriasis in patients using monoamine oxidase inhibitors.

Treatment for Serotonin Syndrome and Opioid Overdose

• Emergency and supportive measures are essential for serotonin syndrome cases.
• Naloxone is effective for opioid overdose; effective doses reported range from 0.06-0.4 mg, potentially requiring up to 2.4 mg if unresponsive.
• For signs of opioid intoxication, administer naloxone IV (0.4-2 mg) with repeat doses as necessary.
• Decontamination can also involve activated charcoal.

Emesis and Phenylpropanolamine (PPA)

• PPA is an appetite suppressant linked to an increased risk of hemorrhagic stroke.
• Toxic doses can occur with 2-3 times the therapeutic dose for PPA, phenylephrine, and ephedrine.
• Pseudoephedrine toxicity symptoms may arise after 4-5 times the therapeutic dose.
• Common in nonprescription nasal decongestants and cold preparations, which often combine antihistamines and cough suppressants.

Mechanism of Action

• PPA and phenylephrine act as direct alpha-adrenergic agonists and have mild beta-adrenergic stimulation effects.
• PPA enhances norepinephrine release, contributing to its sympathomimetic activity.
• Ephedrine and pseudoephedrine exhibit both direct and indirect alpha- and beta-adrenergic activities, resulting in substantial beta-adrenergic stimulation compared to PPA or phenylephrine.

Clinical Presentation of Toxicity

• Major symptoms include:
  • Hypertension due to alpha1-mediated vasoconstriction
  • Headache and confusion
  • Seizures and intracranial hemorrhage
  • Bradycardia or AV block affecting electrical conduction in the heart
  • Possible myocardial infarction

Treatment of Toxicity

• Emergency and supportive measures are critical.
• For hypertension with diastolic pressure > 100-105 mmHg, use vasodilators like phentolamine or nitroprusside.
• Do not administer beta blockers without prior vasodilator treatment; position patients upright.
• For arrhythmias, propranolol or esmolol may be given, but avoid beta blockers in bradycardia associated with hypertension.
• Ipecac-induced emesis, activated charcoal, and cathartics are used for decontamination.
• Urinary acidification enhances elimination for PPA, ephedrine, and pseudoephedrine.

Dextromethorphan and NMDA Receptor Inhibition

• Dextromethorphan and its metabolite inhibit NMDA glutamate receptors, leading to altered mental status and psychoactive effects.
• Inhibition of serotonin reuptake can lead to serotonin syndrome, characterized by confusion, agitation, tachycardia, hypertension, and mydriasis in patients using monoamine oxidase inhibitors.

Treatment for Serotonin Syndrome and Opioid Overdose

• Emergency and supportive measures are essential for serotonin syndrome cases.
• Naloxone is effective for opioid overdose; effective doses reported range from 0.06-0.4 mg, potentially requiring up to 2.4 mg if unresponsive.
• For signs of opioid intoxication, administer naloxone IV (0.4-2 mg) with repeat doses as necessary.
• Decontamination can also involve activated charcoal.

Learn about various respiratory drugs, including Dextromethorphan, PPA, Theophylline, and Anti-inflammatory Agents. Understand their functions, effectiveness, and side effects.