PHARM: Drugs for Asthma/COPD Flashcards
What do adrenergic agonists do? (broad)
Bronchodilator
List 3 non-specific adrenergic agonists.
Epinephrine (beta1, beta2, alpha)
Ephedrine (beta1, beta2, some alpha)
Isoproterenol (beta1, beta2)
List 2 beta-2 specific agonists with quick onset/short duration.
Albuterol
Xopenex
Terbutaline (IV)
List 2 beta-2 specific agonists with slow onset/long duration.
Salmeterol
Formoterol (used with steroids)
What do cholinergic antagonists do? (broad)
bronchodilator
Name 2 cholinergic antagonists.
Atropine
Ipratropium
What are methylxanthines?
bronchodilators with anti-inflammatory activity
Name 2 methylxanthines.
Aminophylline
Theophylline
Name 4 classes of drugs used for inflammation associated with asthma.
1) Cromolyns
2) Corticosteroids
3) Leukotriene receptor blockers
4) Leukotriene synthesis inhibitors
Name an example of a cromolyn.
Cromolyn sodium
Name some examples of corticosteroids.
Budesonide
Fluticasone
Prednisone (oral)
(ones, ides, or compined with “ols”)
Name 2 leukotriene receptor blockers.
Monteleukast
Zafirlukast
Name a leukotriene synthesis inhibitor.
Zileuton
What is the anti-IgE antibody used for asthma/COPD treatment?
Omalizumab
Which class of drugs are used as “rescue medication”? How long is the duration?
selective, quick-onset beta-2 agonists with intermediate duration (3-6 hours)
What class of drugs are used only in combination with inhaled steroids? How long is the duration?
LABAs (long-acting beta2 agonists) that last for over 12 hours
List some LABA + steroid combinations.
Advair (salmeterol + fluticasone)
Symbicort (formoterol fumarate + Budesonide)
How do beta agonists lead to bronchodilation (help asthma)?
- Increase levels of cAMP
- Inhibit release of mediators from mast cells
- Inhibit microvascular permeability
- promote some mucociliary transport
How does increasing cAMP lead to bronchodilation?
Gs Pathway: cAMP activates PKA which inhibits myosin light chain kinase (along with decreased levels of calcium from activation of calcium-activated K+ channels) leading to relaxation
What is the “alternative signaling” pathway of beta2 agonists?
Gq pathway: Increased phospholipase C and input from beta-arrestin2 leads to increased inflammation
What are some adverse reactions to beta agonists?
- N/V
- Headache
- Decreased BP, Increased HR (cardiac arrhythmias)
- Decreased PaO2
- CNS effects (coma, convulsions, agitation, etc)
What is the MOA of antimuscarinics?
Block Ach receptors to reduce airway muscle constriction, decrease mucus secretion, and enhance beta2-mediated bronchodilation
What are some adverse effects of antimuscarinics?
Pupillary dilation
Cycloplegia (on contact)
What is interesting about ipratropium?
it is a tertiary compound (antimuscarinic) that is poorly absorbed and has no significant systemic effects
What is combivent?
combined anti-cholinergic and beta-2 agonist (albuterol + ipratropium bromide)
What is the indication for combivent?
COPD
Methylaxanthines are related to what chemical?
caffeine
What are the major actions of methylaxanthines?
- Increase levels of cAMP (bronchodilation)
- Decrease release of inflammatory mediators
- Block muscle adenosine receptors (prevent bronchoconstriction)
How do methylxanthines increase levels of cAMP?
they block the conversion of cAMP into AMP (breakdown)
The adverse effects of methylxanthines depend on what?
the serum levels
What adverse reactions occur with 5-10 microgram/mL serum levels of methylxanthines?
N/V
Nervousness
Headache
Insomnia
What adverse reactions occur with over 20 microgram/mL serum levels of methylxanthines?
Vomiting Hypokalemia Hyperglycemia Tachycardia Tremor Seizures
Cromolyns may alter the activity of what type of channels?
chloride channels
What are the 4 major actions of cromolyns?
- Inhibit mast cell degranulation
- Inhibit inflammatory response (act on eosinophils)
- Inhibit cough (act on airway nerves)
- Reduce bronchial hyperactivity
What is a reason people may not be adherent to cromolyns?
they taste bad
List some adverse reactions to cromolyns.
COUGH and bronchospasm after inhalation (irritation of trachea) Chest pain (rare) Restlessness (rare) Hypotension (rare) N/V (rare)
List 4 actions of glutocorticoids.
1) Decrease production of inflammatory cytokines
2) Reduce mucus secretions
3) Reduce bronchial hyperactivity
4) Enhance effect of Beta-2 agonists (by increasing transcription of the receptors)
Which syndrome can result from use of glucocorticoids? List some symptoms.
Cushingoid Syndrome
- Weight gain (abdomen, buffalo hump, moon face)
- Thinning and leg/arm muscle weakness
- Thin skin
- Increased acne, facial hair growth, scalp hair loss in women
- Ruddy complexion
- Acanthosis (neck skin darkening)
- Child obesity and poor growth
- High BP
What is the role of LTB4?
neutrophil chemoattractant
Which leukotrienes mimic asthma symptoms (bronchial hyper-reactivity and constriction, mucosal edema, increased mucus secretion)?
LTC4
LTD4
What leukotriene receptor do Zafirlukast and Monteleukast block?
LTD4 receptors
Leukotriene receptor blockers are “effective in some patients” of what subtype of asthma?
aspirin-induced asthma
What are some adverse effects associated with zafirlukast?
GI problems
headache
elevation of liver enzymes (liver and bladder cancer in rodents)
What are some adverse effects associated with monteleukast?
GI problems laryngitis/pharyngitis nausea otitis/sinusitis viral infections increased possible suicidal ideation*
What is the effect that leukotriene synthesis blockers have in asthma patients?
- Decrease smooth muscle contraction
- Decrease blood vessel permeability/leukocyte migration to damaged area
Which CYP is inhibited by (and a substrate for) Zileuton?
CYP1A2 (interacts with theophylline!)
What must be checked when on Zileuton?
LFTs are required, because it causes hepatic enzyme elevation
Use of Zileuton could be connected to what sort of conditions?
inflammation-related conditions like RA and acne
Omalizumab is used for what?
- Reduce severity/frequency of asthma attacks by decreasing the allergic response to triggers
- Reduce requirement for inhaled corticosteroids
What are some adverse effects of omalizumab?
- Serious allergic RXN
- Redness, warmth, itching, bruising in injection site
- Sore throat/cold symptoms
- Increase CV complications
How does the treatment approach differ for asthma and COPD?
corticosteroids do not help and bronchodilators are only partially helpful
What are the 3 main-lines of treatment for COPD?
1) Smoking cessation
2) Bronchodilators
3) Antimuscarinics
What 5 drug classes are contraindicated in airway diseases?
1) Sedatives
2) Beta-blockers
3) Aspirin
4) ACE Inhibitors
5) Local anesthetics with EPI
What is doxapram?
a short-acting respiratory stimulant given IV
What is the MOA of doxapram?
activates peripheral carotid receptors to increase respirations to treat acute hypercapnia in COPD or post-anesthesia respiratory depression
What is the “best” glucocorticoid? Why?
Ciclesonide
- High lipophilicity
- Rapidly cleared from mouth
- Good binding to receptor
- Good brinding to protein
