PHCT Respiratory Drugs Reviewer PDF

PHCT MIDTERMS Week 6: Respiratory Drugs Respiratory Drugs: Dextromethorphan PPA and related decongestants Theophylline Anti-inflammatory Agents Dextromethorphan Found in many over-the-counter cough and cold preparations. Opioid without analges...

PHCT MIDTERMS Week 6: Respiratory Drugs Respiratory Drugs: Dextromethorphan PPA and related decongestants Theophylline Anti-inflammatory Agents Dextromethorphan Found in many over-the-counter cough and cold preparations. Opioid without analgesic effect, no addictive properties Often found in combination products containing antihistamines, Examples: Nyquil, Robitussin DM, Triaminic DM, and Vick decongestants, or acetaminophen. Pediatric Formula 44. Antitussive, cough suppressant Characteristics: Toxic Dose: Dextromethorphan is the d-isomer of 3-methoxy-N- Symptoms usually occur when ingested exceeds 10mg/kg. methylmorphinan, a synthetic analogue of codeine. (The l-isomer Usual recommended adult daily dose: 60-120 mg/d; in children is the opioid analgesic levorphanol) aged 2-5 years, up to 30 mg/d. Has no apparent analgesic or addictive properties and produces Clinical Presentation: relatively mild opioid effects in overdose. Mild intoxication: Clumsiness, Ataxia (lack of muscle Also has anticholinergic properties. coordination), Nystagmus (involuntary movement of eyes), Well-absorbed orally, and effects are apparent within 15-30 Restlessness, Visual and auditory hallucinations. minutes. Severe poisoning: Stupor (reduced responsiveness), Coma, Duration of effect is normally 3-6 hours. Respiratory depression (co-ingestion with alcohol), Pupils may be dilated or constricted, Seizures after ingestions of 20-30 mg/kg. Mechanism of Toxicity: With therapeutic doses taking MAOI (increased level of NE, Both dextromethorphan and its o-demethylated metabolite Epinephrine, Dopamine, Serotonin): Severe hyperthermia, appear to antagonize N-methyl-D-aspartate (NMDA) glutamate Muscle rigidity, Hypertension (excessive vasoconstriction) related receptors. (excitatory neurotransmitter) (inhibit - dissociative & to serotonin syndrome. psychoactive effects → altered mental status, hallucination, and neuro psychotic affects) Treatment: Inhibits reuptake (increased level neurotransmitter) of serotonin, Emergency and supportive measures. may lead to serotonin syndrome (increased level of serotonin Specific drugs and antidotes: Although naloxone (opioid overdose confusion, agitation, tachycardia, hypertension, mydriasis) in antidote) has been reported effective in doses of 0.06-0.4 mg, patients taking monoamine oxidase inhibitors. other cases have failed to respond to as much as 2.4 mg. If the Serotoninergic effects, as well as NMDA glutamate receptor patient exhibits signs of opioid intoxication (CPR → coma, inhibition, may explain the acute and chronic abuse potential of pinpoint pupil, respiratory depression), administer 0.4-2 mg dextromethorphan. naloxone IV, with repeat doses as needed. Decontamination: Activated Charcoal. C/I: emesis PPA & Related Decongestants Phenylpropanolamine (PPA) - also used as an appetite Toxic Dose: suppressant. causes hemorrhagic stroke PPA, phenylephrine, and ephedrine have low toxic ratios. Phenylephrine, Ephedrine, Pseudoephedrine - available in Toxicity after ingestion of 2-3 times the therapeutic dose; nonprescription nasal decongestants and cold preparations. pseudoephedrine: symptoms after 4-5 times the therapeutic Usually also contain antihistamines and cough suppressants dose. Sympathomimetic Drugs (Sympathetic Agonist enhances Patients with autonomic insufficiency or on MAOI may develop sympathetic effects - alpha and beta and dopamine receptor) severe hypertension after subtherapeutic doses. Mechanism of Toxicity: Clinical Presentation: PPA and phenylephrine: Direct alpha-adrenergic agonists. PPA Hypertension (alpha1 - BV - constriction major toxic effect), produces mild β1-adrenergic stimulation and acts in part Headache, Confusion, Seizures, Intracranial hemorrhage, indirectly by enhancing norepinephrine release Bradycardia or AV block (atrioventricular block delay or Ephedrine and pseudoephedrine: Both direct and indirect alpha- interruption in electrical conduction in the atria), Myocardial and beta-adrenergic activity. They clinically produce more beta- infarction. adrenergic stimulation than PPA or phenylephrine 1 PHCT MIDTERMS Treatment: Emergency and supportive measures. Specific drugs and antidotes: o Hypertension: Treat hypertension if the diastolic pressure is higher than 100-105 mm HG. Use phentolamine or nitroprusside (vasodilators) o Caution: do not use beta blockers alone w/o first giving a vasodilator place the patient in an upright position o Arrhythmias (irregular heartbeat): Give propranolol or esmolol (betablockers) o Caution: do not treat AV block or sinus bradycardia associated with hypertension (If the patient has bradycardia, do not administer beta blockers.) Ipecac-induced emesis, activated charcoal, and cathartic for decontamination. Enhanced elimination: Urinary acidification for PPA, ephedrine, and pseudoephedrine. But may also aggravate myoglobin deposition in the kidney if the patient has rhabdomyolysis (damaged skeletal muscle breaks down rapidly) Theophylline Methylxanthine (oral) used for asthma treatment. Clinical Presentation: IV infusions of aminophylline for bronchospasm, congestive heart Acute single overdose (1 take, excessive amounts): Tremor, failure, and neonatal apnea. Anxiety, Tachycardia, Hypokalemia, Hypophosphatemia, Hyperglycemia, Metabolic acidosis, ventricular arrhythmias, Orally used in sustained-release preparations (Theo-Dur, Slo- Status Epilepticus (continuous prolonged seizure without phyllin, Theobid). regaining consciousness), seizures (serum levels > 100 mg/L). Mechanism of Toxicity: Chronic intoxication: Vomiting, Tachycardia, Hypokalemia, Inhibit phosphodiesterase at high levels, increasing cAMP. (Cyclic Hyperglycemia, Hypotension (rare), Seizures (serum levels, 40-60 adenosine monophosphate) mg/L). Stimulate beta-adrenergic receptors. (Beta 2 – lungs) Treatment: Release endogenous catecholamines. Emergency and supportive measures. Antagonist of adenosine receptors. Specific drugs and antidotes: Toxic Dose: o Use low dose propranolol, 0.01-0.03 mg/kg IV (non- Acute single dose of 8-10 mg/kg produces therapeutic level of 15- selective beta blocker) 20 mg/L. o Esmolol, 25-50 µg/kg/min (non-selective beta blocker) Acute oral overdose of more than 50 mg/kg can result in levels o Use beta blockers cautiously in patients with a prior history above 100 mg/L and significant toxicity. of asthma or wheezing Ipecac-induced emesis, activated charcoal, and cathartic for decontamination. Bronchodilators - Β2 agonists Mechanism of action: Stimulate ß2-receptors → activating adenylyl cyclase → increases intracellular production of CAMP → bronchodilation, improved mucociliary clearance, and reduced inflammatory cell mediator release suffix –”terol” Uses Bronchodilators–non-selective Short acting rapid onset first line in the Tx of acute o reserved for special situations (cardiac stimulation) Salbutamol (Albuterol) exacerbation of BA primary reliever medication Drugs Dose Long-acting slow onset prophylactic agent (acute Epinephrine SC (0.4 mLof Onset: 15 minutes attacks) for controlling nocturnal 1:1000 solution) Duration: 60–90 attacks controller medication inhaled -320 g per mins Long acting with rapid onset controller usually given through puff inhalation Ephedrine Lower potency Isoproterenol Inhaled: 80–120 g Onset: 5 minutes Duration: 60–90 mins Selective B2 agonists Drugs Route Remarks Albuterol Oral, MDI metered dose inhaler Terbutaline SC inj. (0.25 mg) For severe asthma Metaproterenol Oral, MDI Salmeterol& Formoterol long-acting DOA: (Long-acting beta 12 hours agonist) 2 PHCT MIDTERMS Anticholinergic/Antimuscarinic Bronchodilators o Clinical characteristics: Useful in COPD, better safety profile Anticholinergic: tachycardia, constipation, flushing, urinary compared to β2 agonists. retention, dry mouth Drugs Characteristics Duration of Action o Ipratropium, Tiotropium. ipratropium bromide quaternary ammonium 3-5 hrs derivative of atropine → o Datura stramonium/ D. metel prototype of anticholinergic drug o Mechanism: Block muscarinic receptors, preventing acetylcholine binding, blocking airway smooth muscle tiotropium longer-acting selective 24 hrs contraction. antimuscarinic agent Anti-inflammatory Agents Mast cell stabilizers Class Examples Uses Mast cell stabilizers Cromolyn sodium (disodium cromoglycate) Also used in allergic rhinoconjunctivitis storage of histamine activation → degranulation prophylaxis of Exercise Induced asthma → bronchoconstriction Nedocromil o Side effects: bronchospasm (acute administration) o Management: pre administration of β2 agonist o Mechanism: Stabilizes mast cell membrane by increasing chloride ion conduction thus inhibiting cellular activation Class Example/s Mechanism of action Adverse effect/s Lipoxygenase inhibitor Zileuton inhibits 5 lipoxygenases thereby Hepatotoxic preventing leukotriene synthesis Check ALT (liver enzyme) (inflammatory mediator) initiation monthly (3months) 2-3 months for 1 year annually HA, abdominal pain, asthenia, nausea, dyspepsia and myalgia. Leukotriene receptor blockers Montelukast Zafirlukast prevents the binding of LTD4 to Churg-Strauss syndrome (hepatotoxic) cysteinyl leukotriene 1 (CysLT1) (Inflammation of small to medium- Used in NSAID induced asthma receptor thus inhibiting its effects sized blood vessels) on airways. (Prevent leukotriene receptors from binding.) Corticosteroids o Mechanism of Action: Corticosteroids bind to glucocorticoid receptors on the cytoplasm of cells. The activated receptor regulates transcription of target genes. o For prevention of nocturnal asthma: oral or inhaled corticosteroids are most effective when given in the late afternoon. o Aerosol treatment: is the most effective way to decrease the systemic adverse effects of corticosteroid therapy o Side effects: inhaled topical corticosteroids can cause oropharyngeal candidiasis. o Management: gargle water and spit after each inhaled treatment. ▪ Budesonide ▪ Oral: Prednisone ▪ Fluticasone ▪ Beclomethasone 3