Respiratory Drugs Flashcards
beta2 adrenergic agonists drugs
- Terbutaline
- Albuterol
- Levalbuterol
- Salbutamol
- Salmeterol (long-acting)
beta2 adrenergic agonists MOA
-beta receptors coupled to stimulatory G proteins
-activate adenyl cyclase which increases the production of cAMP (adenosine monophosphate) bronchodilation
-reduced intracellular calcium release and alters membrane conductance
Primary Effect – dilate bronchi by a direct action of b2 adrenergic receptors
-smooth muscle relaxation and bronchodilation
-inhibits mediator release from mast cells
-increase mucous clearance by action of cilia
beta2 adrenergic agonists PK/PD
- rapid onset –> within minutes
- short DOA –> 4-6 hours
- short or long acting
beta2 adrenergic agonists dose/route
Routes:
- inhalation or aerosol
- powder or nebulized
- orally or injected (SQ)
beta2 adrenergic agonists clinical uses
-good for asthma use as rescue inhaler
beta2 adrenergic agonists effects/considerations
- side effect profile minimized by inhalational delivery (bc directly at site of action)
- tremors
- tachycardia
- vasodilation
- metabolic changes - hyperglycemia, hypokalemia, hypomagnesemia
albuterol PK/PD
- DOA –> 4 hours with some relief evident up to 8 hours
- 2 isomers –> R-albuterol levalbuterol has more affinity for beta2 & S-albuterol has more affinity for beta1
albuterol dose/route
- administered via metered dose 100mcg/puff
- 2 puffs Q4-6H
- nebulizer 2.5-5 mg in 5 mL saline
albuterol clinical use
asthma rescue inhaler
albuterol effects/considerations
-additive effect with volatile anesthetics on bronchomotor tone –> get increased bronchodilation
-preferred selective beta2 agonist and used most commonly in the OR
-if patient takes albuterol for asthma, good practice to have them take a few puffs before going to OR
Common SE:
-tachycardia
-hypokalemia
-anesthetic use – 4 puffs blunt AW responses to tracheal intubation in asthmatic patients
Metaproterenol (Alupent)
- treatment of asthma
- administered via metered dose
- do not exceed 16 puffs/day
Pirbuterol (Maxair)
- treatment of asthma
- 2 puffs (400 mcg) via metered dose
- do not exceed 12 puffs/day
terbutaline dose
- administered oral, SQ, inhaled
- SQ dose 0.01 mg/kg (peds); 0.25 mg Q15min (adults)
- metered dose inhaler 16-20 puffs/day (each dose is 200mcg)
- SQ admin = similar effects to EPI
terbutaline clinical uses
- treat asthma
- tocolytic to slow down labor (smooth muscle/uterine relaxation)
Long-acting beta2 adrenergic agonists
Salmeterol (combo steroid and b2 agonist)
Formoterol
Long-acting beta2 adrenergic agonist MOA
- have lipophilic side chains that resist degradation
- salmeterol = fluticasone (steroid) + salmeterol (b2 agonist)
Long-acting beta2 adrenergic agonist PK/PD
-DOA 12-24 hours
Long-acting beta2 adrenergic agonist clinical use
-good for prevention of asthma exacerbation but not acute flare-up/rescue
Anticholinergic (Muscarinic Receptor Antagonist) drugs
- Atropine
- Ipratropium bromide
- Tiotropium
Anticholinergic (Muscarinic Receptor Antagonist) MOA
- competitive antagonists at muscarinic ACh receptors
- M1 and M3 expressed in lung and most important in mediating smooth muscle relaxation + decreased mucus gland secretions
- by antagonizing endogenous ACh broncho-relaxation + decreased mucus secretions
Anticholinergic (Muscarinic Receptor Antagonist) clinical uses
- treatment of COPD
- secondary line of treatment for asthma in patients resistant to beta agonist or significant cardiac disease
Anticholinergic (Muscarinic Receptor Antagonist) effects/considerations
Anticholinergic effects:
- tachycardia
- nausea
- dry mouth
- GI upset
atropine PK/PD
highly absorbed across respiratory epithelium
atropine dose
-1-2 mg diluted in 3-5 mL saline via nebulizer
atropine effects
-formerly 1st line treatment for asthma Anticholinergic effects: -tachycardia -nausea -dry mouth -GI upset
Ipratropium bromide MOA
- quaternary ammonium salt derivative of atropine
- antagonizes effect of endogenous ACh at M3 receptor subtypes
Ipratropium bromide PK/PD
- slow onset 30 min
- DOA 4-6 hours
- not significantly absorbed compared to atropine
Ipratropium bromide dose
-admin via metered dose inhaler 40-80 mcg in 2-4 puffs via nebulizer
Ipratropium bromide effects
-inadvertent oral absorption (when pt swallows excess med) causes dry mouth and GI upset
Tiotropium PK/PD
- long acting
- not significantly absorbed across respiratory epithelium which results in few S/E
Tiotropium clinical use
approved by FDA for COPD
Phosphodiesterase Inhibitors (Methylxanthines) drugs
Theophylline
Aminophylline
Phosphodiesterase Inhibitors (Methylxanthines) MOA
-nonspecific inhibition of phosphodiesterase isoenzymes (types III and IV) which prevents cAMP degradation in airway smooth muscle cell as well as inflammatory cells airway relaxation + bronchodilation + no histamine release from mast cells
Phosphodiesterase Inhibitors (Methylxanthines) PK/PD
- metabolized in liver
- excreted in kidney
- susceptible to drug-drug interactions due to metabolism by CYP450 (like cimetidine and antifungals or other CYP 450 inhibitors)
Phosphodiesterase Inhibitors (Methylxanthines) clinical use
- COPD
- Asthma
Phosphodiesterase Inhibitors (Methylxanthines) effects/considerations
-huge side effect profile and narrow therapeutic index ; also need to monitor for toxic blood level
-theophylline plasma level 10-20 mcg/mL (toxic at >20 mcg/mL)
-caution with halothane (combo sensitizes heart to epi and more prone to arrhythmias)
Side Effects:
-HA
-N/V
-irritability/restlessness
-insomnia
-cardiac arrythmias
-seizures
-Stevens Johnson Syndrome
Inhaled Corticosteroids drugs
Beclomethasone
Triamcinolone
Fluticasone
Budesonide
Inhaled Corticosteroids MOA
- alter genetic transcription
- increases transcription of genes for b2 receptor and anti-inflammatory proteins
- decreases transcription of genes for pro-inflammatory proteins
- induce apoptosis in inflammatory cells (eosinophils, TH2 lymphocytes)
- indirect inhibition of mast cells over time
- reverses many features of asthma
- reduce number of inflammatory cells in airways and damage to epithelium
- vascular permeability reduced which decreases airway edema
- overall reduction in airway hyper-responsiveness
Inhaled Corticosteroids PK/PD
- 25% of inhaled reaches airway
- 80-90% of inhaled dose reaches oropharynx and is swallowed (unless mouth is rinsed after using inhaler)
- higher airway concentration than same dose given PO
Inhaled Corticosteroids clinical use
- major preventative treatment for patients with asthma (considered most important drug in management of asthma)
- used as suppressive therapy, not a cure
Inhaled Corticosteroids effects/considerations
-may consider use of corticosteroid admin 1-2 hours pre-op
-prolong response of beta agonists
-may consider 5-day preop course of combined corticosteroid and albuterol to minimize risk of intubation evoked bronchospasm
-systemic effects decreased through inhalation
Side Effects:
-oropharyngeal candidiasis
-osteopenia/osteoporosis
-delayed growth in children
-hoarseness
-hyperglycemia
Mast Cell Stabilizer drug
cromolyn
Mast Cell Stabilizer MOA
- inhibits antigen-induced release of histamine
- including release of inflammatory mediators from eosinophils, neutrophils, monocytes, macrophages, lymphocytes, and leukotrienes from pulmonary mast cells
- inhibits immediate allergic response to an antigen but not the allergic response once it has been activated
Mast Cell Stabilizer PK/PD
- 8-10% enters systemic circulation
- takes 7 days to see effect
Mast Cell Stabilizer dose
- inhalation
- take 4x daily
Mast Cell Stabilizer clinical use
- prophylactic treatment of bronchial asthma
- does not relieve allergic response after initiation
- not used as rescue inhaler
Mast Cell Stabilizer effects/considerations
-side effects rare Infrequent but serious side effects include: -laryngeal edema -angioedema -urticaria -anaphylaxis
Leukotriene Inhibitors
Zileuton Montelukast -leukotrienes – synthesized from arachidonic acid when inflammatory cells activated -bronchial asthma -not effective for acute asthma attacks -few extrapulmonary effects
Zileuton MOA
-blocks biosynthesis of leukotrienes from arachidonic acid
Zileuton PK/PD
- low bioavailability
- low potency
Zileuton clinical use
-produces bronchodilation, improves asthma symptoms, shown long term improvement in PFT
Zileuton effects/considerations
- significant adverse effects
- hepatotoxic
- not widely used
Montelukast MOA
- blocks mechanism of bronchoconstriction and smooth muscle effects
- blocks ability of leukotrienes to bind to Cysteinyl-leukotriene 1 receptor
Montelukast clinical use
-improve bronchial tone, pulmonary function, and asthma symptoms
Montelukast effects/considerations
- caution with co-admin with warfarin which could result in prolonged PT
- well tolerated/few side effects
Anti-IgE Antibodies drug
Omalizumab
Anti-IgE Antibodies MOA
- humanized mouse monoclonal antibody
- binds to IgE; decreases quantity of circulating IgE and prevents binding of IgE to mast cells
- removal of IgE antibodies from circulation to mitigate acute response of inhaled allergen
Anti-IgE Antibodies dose
-given SQ for 2-4 weeks/parenterally infused
Anti-IgE Antibodies clinical use
- for IgE mediated allergenic responses
- given in early and late phase of asthmatic response
Anti-IgE Antibodies effects/considerations
- expensive and inconvenient
- down-regulation of receptors occurs in response to lower levels of circulating IgE; receptors on mast cells, basophils, and dendritic cells are down-regulated
- rare effect – triggering of immune response
