Drugs for treating asthma & COPD Flashcards
Leukotriene modifiers used to treat asthma & COPD
Leukotriene receptor antagonist:
Montelukast
5-LO inhibitor:
Zileuton
Antiinflammatory drugs used for asthma & COPD
Steroids:
Beclomethasone
Prednisone
Histamine modulators:
Cromolyn
Omalizumab
PDE4 inhibitors:
Roflumilast
Bronchodilators used to treat asthma & COPD
B2 agonist:
Albuterol
Salmeterol
Methylxanthines:
Theophylline
Aminophylline
Muscarinic receptor antagonists:
Ipratropium
Tiotropium
Factors causing bronchoconstriction in asthma
M3 receptors
Mediators released from inflammatory cells:
Histamine
Leukotrienes
Iatrogenic: Beta blockers NSAIDS Muscarinic receptor agonists Anticholinesterases
Glucocorticoids MOA
Glucocorticoids- suppress inflammation, decrease bronchial hyper responsiveness, most effective antiasthmatic
Used to treat mild to severe persistent asthma
Steroids used in asthma
Inhalation: Beclomethasone, Fluticasone
Oral: Prednisone
Inhaled steroids used in asthma MOA
Delivered to site of action-smaller doses- decrease side effects
Rapidly inactivated when absorbed
Inhaled steroids used in asthma side effects
Oral candidiasis
Hoarseness
The small risk of other effects (altered bone metabolism) are outweighed by risks of not controlling severe asthma
Oral or parental steroids used in asthma
Prednisone
Methylprednisolone (oral & parenteral)
Roflumilast MOA
PDE4 metabolized cAMP in inflammatory cells
Roflumilast is a selective inhibition of PDE4; inhibition of PDE4 leads to increased intracellular levels of cAMP and a reduction in inflammation
Not a bronchodilator
Roflumilast administration & elimination
Good oral bioavailability
Metabolized to an N-oxide which is active
Metabolized in the liver
Roflumilast adverse effects
Nausea
Diarrhea
Weight loss
Headache
Roflumilast drug interactions
Inhibitors of P450 enzymes will increase blood levels of drug
Inducers of P450 enzymes will decrease blood levels of drug
Zileuton MOA
Blocks the enzyme 5-lipoxygenase- decreasing leukotriene synthesis
Blocks infiltration of inflammatory cells & prevents bronchoconstriction
Zileuton adverse effects
Hepatitis- monitor liver function; contraindicated in patients w/ liver disease or increased liver enzymes
Upset stomach
Zileuton drug interactions
Inhibits P450 so increases Warfarin, Propanolol, and Theophylline conc.
Albuterol administration
Bronchodilator Inhaled for acute relief (present in slower onset oral form) Onset: 5-15min. Peak: 30min. Duration: 6 hours
Salmeterol administration
Bronchodilator Inhaled Preventative; not used for acute bronchospasm Onset: 30-50min. Peak: 3hrs. Duration: 12+hrs.
Bronchodilator MOA
Activation of B2 receptors- increase adenylyl cyclase activity- increase intracellular cAMP levels- bronchodilation
Bronchodilator adverse effects
Anxiety, tremor, restlessness, tachycardia, & hypokalemia more common with oral & parenteral administration
Regular use can lead to drug tolerance & an increase in exacerbations; corticosteroids enhance response to B2 agonists
Bronchodilator indications
Asthma & COPD
Prevention of exercise-induced asthma
Emergency treatment (status asthmaticus) together with systemic glucocorticoids (NOTE: Not Salmeterol)
Methylxanthines
Theophylline
Caffeine
Theobromine
Aminophylline (theophylline ethylenediamine)- contains 85% theophylline- more soluble// rapid infusion of aminophylline causes cardiac arrest & death
Methylxanthines MOA
Smooth muscle relaxation; important in bronchi
CNS stimulation- decrease drowsiness (low doses); convulsions (high doses)// increased sensitivity of medullary respiratory centers to CO2// nausea & vomiting mediated by CNS actions
Cardiovascular- tachycardia (high conc.)// decreased peripheral vascular resistance
Diuretic actions- similar to thiazides
Phosphodiesterase inhibition- increased cAMP
Adenosine receptor blockade
Methylxanthines indications
Reversible airway obstruction due to asthma or other chronic lung disease
Methylxanthines adminstration & elimination
Dose based on serum levels & patient response
Absorption- rapid and complete orally// sustained release preparations- decreased fluctuations between doses & increased compliance
Elimination- first order but at high conc. ZERO order// eliminated primarily by hepatic metabolism (90%)
Factors affecting Theophylline half-life
Factors that increase:
Cimetidine, macrolide antibiotics, hepatic cirrhosis, premature infants, oral contraceptives
Factors that decrease:
Cigarette smoking, phenytoin, barbiturates
Methylxanthines adverse effect
Mild- nausea, vomiting, headache, nervousness, insomnia
Moderate- mild symptoms with sinus tachycardia & occasional PVCs
Severe- serious arrhythmias, seizure, death
Methylxanthines contraindications
Hepatic or cardiac dysfunction
Seizure disorders
Peptic ulcer disease
