Pulm Drugs Flashcards
Medicates for acute exacerbations?
SABA (albuteral) Short acting anticholinergics (ipratropium) systemic corticosteroids
MEdications for maintenance treatment of asthma?
ICS LABA (+ICS) Cromolyn and nedocromil LT modifiers (Montelukast for example or Zileuton) Omalizumab (allergic asthma if all else fails)
Medications for maintenance of COPD?
Long-acting anticholinergics LABA (can see ICS too)
In general, what agents are commonly used for COPD and Asthma? Categorical
1) Bronchodilators: Beta2agonists, Anticholinergics, Theophylline 2) Anti-inflammatory agents: steroids, cromolyn and nedocromil, Leukotriene modifiers, or Omalizumab
What is the mechanism of beta2 agonists?
stimulates B2 receptors to increase cAMP and leads to SM relaxation, bronchodilation, mast cell destabalization, and skeletal muscle stimulation
What are the short acting beta agonists? What is their clinical use?
Albuterol (acute releif and treatmnent of Ashtma and COPD) Terbutaline - systemic injections and more side effects Used for acute exacerbation, Exercise-induced asthma, and Acute COPD
What are the clinical uses for LABA?
maintenance therapy for prevention of bronchospasm in asthma (MUST be used with inhaled corticosteroids) Maintenance for prevention in COPD
What are side effects of beta agonists?
Tachycardia and palpitations transient decrease in serum K Tremors Lactic acidosis at very high doses of Albuteral Increased risk of asthma-death with LABA used alone
what is the mechanism for anticholinergics?
block M1 and M3 receptor activation so blocks Ach from activating receptor to increase cellular levels of cGMP and cause bronchodilation AND block M2 activation to stop further release of Ach
How are the anticholinergics used clinically?
short acting: used for acute exacerbations of asthma and COPD and maintenance treatment of bronchospasm associated with COPD Long acting: maintenance of bronchospams in COPD only!!
What are the anticholinergics used?
Short acting = Ipratropium Bromide Long acting = Tiotropium!! (and also aclidinium bromide)
what are side effects of anti-cholinergics?
blurred vision, dry mouth, nausea, urinary retention, CNS effects, tachycardia Increased CV events!
What are the Methylxanthins?
Theophylline (PO) and Amniphylline (IV)
mechanism of Methylxanthines??
non-selective inhibitor of PDE leads to increased cAMP and cGMP for bronchodilation Has additional effects of regulating inflammatory cells and is competitive antagonist of Adenosine (so stimulates endogenous catecholamine release onto Beta 2 for additional dilation) **VERY NARROW THERAPEUTIC WINDOW
Clinical use of methylxanthines?
acute exacerbation of asthma when all else fails treatment of symptoms and reversible airflow obstruction associated with chronic asthma and COPD/Emphysema
Side Effects of Methylxanthines?
N/V and gastric upset (heartburn) Tachyarrhythmias!!!! (catecholamine release on heart) Jitteriness, insomnia, headache and seizures!
mechanism of corticosteroids?
Glucocorticoid combines with receptor and acts as a transcription factor that leads to 1) activation of IkBeta which inhibits NFKbeta to decrease signals for production of inflammatory proteins 2) binds AP1 gene and decreases transcription of pro-inflammatory mediators like TNF and IL2
what are the clinical effects and clinical uses of corticosteroids?
Effects: reduce inflammatory cell activation, recruitment, and infiltration and decrease vascular permeability Clinical use: - exacerbation of asthma/COPD - maintenance to prevent bronchospasms and symptoms of asthma and COPD -allergic rhinitis
what are the acute side effects of steroids? more chronic side effects? What effects with inhaled steroids?
Salt/water retention, hyperglucemia, HTN Chronic - HPA axis suppression, bone resporption, skel muscle myopathy, pancreatitis, cataracts, skin thinning, growth retardation, etc Inhaled - oral thrush and hoarseness
what is the mechanism of cromolyn and nedocromil?
Mast cell stabilizers inhibit degranulation in response to stimuli, activation and release of mediators, and neurally mediated bronchoconstriction as additional dilatory effect
clinical use for cromolyn and nedocromil?
long term for prevention of symptoms of asthma - good for mild asthma Preventative treatment prior to exposure to allergen or exercise
Side effects of cromolyn and nedocromil?
relatively safe! cough and wheezing and bad taste in mouth with nedocromil
What are the leukotriene modifiers?
LT receptor Antagonists: Zafirlukast and Montelukast (=singular - 1/day!) 5-LPO inhibitor (block conversion of arachadonic acit to LT) = Zileuton
clinical use for LT modifiers?
long term control and prevention of symptoms in mild-persistent asthma allergic rhinitis
Side effects of LT modifiers?
LT receptor antagonists (Zafirlukast and montelukast) = HA, nausea and abdominal pain 5-LPO inhibitor (Zileuton) = Liver toxicity and Hyperbilirubinemia
Mechanism of Omalizumab?
blocks Fc portion of IgE antibody and prevents its binding to mast cells etc blocks IgE release of mast cells and decreases levels of IgE given as subcutaneous injections
clinical use of omalizumab?
treatment of allergic asthma that’s not well controlled with use of corticosteroids Dosing depends on baseline IgE
Side effects of OMalizumab?
ANAPHYLAXIS!!!!!! given as Sub-Q injection in monitored setting
Where are the 3 different H receptors found?
H1 = lung, vascular SM, vascular endothelial cells, and nerves H2= stomach H3 = CNS
mechanism of antihistamines? Differences between generations?
competitive antagonist for H1 receptor and prevents binding of histamine First Generation = lipophilic and non-selective with anticholinergic effects (ex. anti-emetic) Second Generation = specific to peripheral H receptors
clinical use of anti-histamines?
*most effective if taken BEFORE allergen exposure allergic reactions and rhinitis, and first generation are anti-emetic
Side effects of anti-histamines?
Anti-cholinergic “mad as a hatter….” GI - nausea and ab pain CNS - sedation and drowsiness
common drugs that are anti-histamines?
Diphenhydramine = benedryl Alkylamines = anticholinergic effect so used in cough medicines Promethazine = High sedation and high anti-cholinergic Cetrizine = Zyrtec Loratidine = Clariton Fexofenatidine = Allegra
what are the classes of anti-tussives?
1) Opioids 2) Dextromethorphan 3) Benzonatate (Tesslon pearls) 4) Expectorant = Guaifenesin
Mechanism of opioids? Dextromethorphan?
[Opioids = used at lower doses than analgesics and so risk of resp distress is low] both: increases threshold to cough in respiratory cough centers in medulla and nucleus tractus solitarous
side effects of dextromethorphan?
CNS effects at high doses include confusion, excitation, nervousness, and irritability … can even see respiratory depression at high doses = bc some NMDA receptor antagonist activity DO NOT USE in patients with MAOIs or SSRIs bc can cause Serotonin Syndrome
Mechanism of Benzonatate?
anesthetic effect on stretch receptors of vagal afferent fibers in bronchi, alveoli and pleura - blocks cough reflex and stops transmission of signal of cough reflex
mechanism, use and side effects of Guaifenesin?
mechanism - loosens and thins lower resp secretions Used for symptomatic relief of productive coughs Side effects - dizziness, N/V, and diarrhea (from sugar its given with)
