A 67-year old man is admitted to the hospital for exacerbation of his chronic obstructive pulmonary disease. He is currently intubated and receiving high dose albuterol therapy by continuous nebulization. Which of the following is serious adverse effect that can develop with this treatment?
A. Miosis B. Constipation C. Bradycardia D. Hypoglycemia E. Hypokalemia
Hypokalemia-the pharmacology of b2-adrenoceptor agonistschemistry o chemical derivatives of the catecholamines norepinephrine and epinephrine o levalbuterol is the r-isomer of albuterol; arformoterol is the r,r-isomer of formoterol pharmacokinetics o oral, parenteral, and inhalational administration drugs are best delivered inhalationally because this route leads to the greatest local effect in airway smooth muscle with the least toxicity typically, 80-90% of the total aerosol dose is deposited in the mouth or pharynx bronchial deposition is increased by slow inhalation of a nearly full breath and by more than 5 seconds of breath-holding at the end of inspiration duration of action ranges from 3-12 hrs depending on the chemical modifications present in the drug molecule (prevents degradation of the drug by catechol-o-methyl transferasecomt) pharmacodynamics o mechanism of action b2-adrenoceptor agonist especially on airway smooth muscle cells receptor activates adenylyl cyclase and stimulates formation of intracellular camp o this results in numerous biochemical changes in target cells lowering of [ca2+]intracellular by active removal from the cytosol into intracellular stores and out of the cell potent inhibition of the phospholipase c-inositol triphosphate (plc-ip3) pathway inhibition of myosin light chain kinase activation activation of myosin light chain phosphatase opening of large conductance ca2+-activated k+ channels (kca), which repolarizes the smooth muscle cell act as functional agonists reverse bronchoconstriction irrespective of the contractile agent o extremely important fact in asthma, which has numerous bronchoconstriction-promoting agents pharmacological actions/effects relaxes airway smooth muscle rapidly decreases airway resistance inhibits release of bronchoconstricting mediators from mast cells inhibits microvascular leakage increases mucociliary transport by increasing ciliary activity reduces neurotransmission in human airway cholinergic nerves by inhibiting acetylcholine release (action on presynaptic 2-adrenoceptors) major therapeutic moa in copd clinical pharmacology o clinical uses bronchodilator treatment of choice in asthma inhaled short-action drugs are the most widely used and effective due to their functional antagonism of bronchoconstriction o albuterol is the prototype of this group o drugs of choice in treatment of acute severe asthma o should be used on an as needed basis for the relief of symptoms in cases of mild asthma o when inhaled from pressurized metered-dose inhalers (pmdi) or dry powder inhalers (dpi) they are convenient, easy to use, rapid in onset, and without significant systemic adverse effects o effective in protecting against various challenges, such as exercise, cold air, and allergens inhaled long-acting drugs (laba) improve asthma control and provide sustained bronchodilator action (>12 hrs) and bronchoprotection o salmeterol is the prototype of this group o should never be used alone because they do not treat the underlying chronic inflammation should be used in combination with inhaled corticosteroids (ics), preferably in a fixed-dose combination inhaler bronchodilator treatment in copd laba are used for these cases o used as needed in mild copd, or daily in severe copd o they are used alone or in combination with anticholinergics or ics o adverse effects/toxicity most are dose related and due to stimulation of extrapulmonary b2-adrenoceptors especially common with oral and parenteral administration possible development of tolerance (desensitization, subsensitivity) seen with continuous therapy due to down-regulation of b2-adrenoceptors can be prevented by corticosteroids albuterol serious reactions o hypersensitivity reactions, paradoxical bronchospasm, htn, angina, mi, hypokalemia, arrhythmias, metabolic acidosis (nebulized use) common reactions o tremor, nervousness, headache, nausea, tachycardia, muscle cramps, palpitations, insomnia, dizziness, throat irritation, uri symptoms, cough, bad taste, salmeterol serious reactions o paradoxical bronchospasm, asthma exacerbation, asthma-related death, anaphylaxis, angioedema, laryngospasm, arrhythmias, htn common reactions o headache, throat irritation, nasal congestion, rhinitis, tracheitis/bronchitis, pharyngitis, urticaria, rash, palpitations, tachycardia, tremor, nervousness carries a black box warning regarding asthma-related death risk and appropriate use in pediatric/adolescent patients o contraindications albuterol drug combinations o phenothiazines pregnancy/lactationcategory c/precaution (probably safe) salmeterol asthma monotherapy, acute asthma drug combinations o phenothiazines pregnancy/lactationcategory c/precaution (safety unknown)