mdunk12's 2016-04-11 18:32
1a: Asthma Medications/MOA
1a: Asthma Medications/MOA = Section
Monoclonal AB against serum IgE Omalizumab -- used in allergic asthma with elevated serum IgE
What is theophylline Methylxanthine derivative that effectively blocks the action of phosphodiesterase to inhibit cAMP breakdown --> bronchodilation
What are some of the inhaled anticholinergics used for asthma? Ipratropium, tiotropium, indacaterol
What are the various beta-2 agonists used in asthma (SABAs and LABAs) The short-acting beta agonists (SABAs) are albuterol, levalbuterol, and pirbuterol. The long-acting beta agonists (LABAs) are salmeterol, formoterol, and arformoterol. The ones to remember are albuertol and salmeterol, fomoterol.
What are the mechanisms of the leukotriene modifiers? CysLT1 (leukotirene receptor) receptor antagonists (montelukast, zafirlukast) and lipooxygenase inhibitors (zileuton). CysLT1 is the site of action of leukotrienes C4/D4/E4 and can cause bronchoconstriction.
What is Zileuton 5-liopoxygenase pathway inhibitor; blocks conversion of arachidonic acid to leukotrienes (C4, D4, E4)
What are Monelukast and Zafirlukast used for Leukotriene receptor (CysLT1) inhibitors used for all types of asthma --> particularly good in Aspirin-exacerbated respiratory disease
How do Ipratoprium or Tiotropium work competitively block M3 receptors on bronchiolar smooth muscle cells to inhibit bronchoconstriction
What are the effects of inhaled steroids in asthma Inhibit production of nearly all cytokines, particularly target NF-kB pathway and production of TNF-alpha, which stimulates many inflammatory cytokines
When are inhaled steroids indicated in asthma 1st line therapy for chronic asthma, particularly with chronic beta agonist use
What is the potentiating effect of steroids used with beta agonists Steroids are believed to increase expression of beta 2 receptors and thus potentiate the effects of LABAs
What are the (3) perceived effects of inhaled steroids in asthma (1) Anti-inflammatory; (2) Block phospholipase A2 in arachadonic acid metabolism; (3) Potentiate beta 2 agonists
MOA of Cromyln Stabilize the plasma membrane of mast cells and eosinophils to prevent degranulation and release of histamine & leukotrienes (note that this mechanism does NOT involve bronchodilation)
When is Cromyln used? NOT used acutely. Largely used prophylactically for asthma
Name (5) glucocorticoids used in asthma Fluticasone, budesonide, beclomethasone, mometasone, ciclesonide
When are inhaled glucocorticoids used in asthma? Prophylaxis, and NOT typically during acute exacerbations
When are inhaled muscarinic antagonists used? Asthma and COPD (particularly to manage acute bronchoconstriction)
When are systemic steroids used in asthma Parenteral administration during severe acute asthma attacks (status asthmaticus) --> avoided in children whenever possible
What are the clinical uses of Theophylline slow release for control of nocturnal asthma, COPD
How is methacholine used in asthma assessment Methacholine challenege test is used to assess "reactivity" of airways --> administer inhaled methacholine, observe for 20% reduction in FEV1
1b: Asthma Medications ADR
What are the most common ADR of short and long acting beta2 agonists Skeletal muscle tremors, tachycardia (high doses), arrhythmia (high doses); NOTE -- long acting agents have higher risk of CV events, particularly in COPD patients
What patients are more susceptible to beta2 agonists ADR COPD patients
What asthma drug is not widely used due to extremely narrow therapeutic index Theophylline
What are the major ADR of Theophylline Arrhythmia, Neurotoxicity (seizures, insomnia, tremor), Hypotension
What are the notable drug interactions of Theophylline metabolized by and inhibits CYP450, blocks adenosine receptors (effective for SM dilation)
What are the ADR of inhaled glucocoritcoids? Oral/pharyngeal candidiasis; minimal systemic ADR but can cause adrenal supression
What are the ADR of leukotriene receptor antagonists Montelukast and zafirlukast are well tolerated with minimal ADR
What is the celebrated ADR of Zileuton hepatotoxicity with elevated LFTs
2a: Pulmonary Hypertension Pharmacology
Role of prostacyclins in pulmonary hypertension Inhibit platelet activation and have some anti-proliferative properties (patients with pulmonary hypertension seem to make less of this)
Role of nitric oxide (NO) in pulmonary hypertension Inhibits platelet activation, has anti-proliferative properties, and is vasodilatory (again, pulmonary hypertension patients seem to make less of this)
Role of endothelin-1 in pulmonary hypertension Potent vasoconstrictor, inducer of vascular smooth muscle proliferative, and promotes inflammation (pulmonary hypertension patients seem to have MORE of this)
Role of endothelin-A receptor vs. endothlin-B receptor ET-A receptor promotes vasoconstriction, whereas ET-B receptor promotes vasodilation.
Name of the prostacyclin analog EpoPROSTanol (others include trePROSTinil and iloPROST)
Major concerns about the prostacyclin analogs Expensive, must be given by IV pump, and cannot be interrupted in dose (with risk of death if there is a sudden interruption)
Names of the endothelin receptor antagonists Bosentan and ambrisentan
Mechanism of the endothelin receptor antagonists Bosentan blocks ET-A and ET-B, whereas ambrisentan blocks ET-A only
What concerns might the metabolism of endothelin receptor antagonists create for people on other drugs? They act as P450 substrates and inducer, which can make oral contraceptives less effective.
Major ADRs of endothelin receptor antagonists Liver damage, highly teratogenic (damaging to a fetus), can cause sexual problems (testicular atrophy.
Names of the PDE-5 inhibitors Sildenafil and tadalafil
Mechanism of the PDE-5 inhibitors Inhibit cGMP breakdown (by inhibiting phosphodiesterase), which potentiates nitric oxide (NO).
Problems with giving PDE-5 inhibitors and endothelin receptor antagonists TOGETHER Bosentan can induce P450 enzymes and lower the concentration of PDE-5 inhibitors.
Major ADRs of PDE-5 inhibitors Visual disturbances (sudden loss of vision; blue vision).
When are PDE-5 inhibitors contraindicated Do NOT give this with nitrates, alpha blockers (worries about hypotension), and other drugs that affect P450 enzymes
Major ADRs of prostacylcin analogs Flushing, jaw pain
3a: Cough, cold, and allergy pharmacology
What are the differences between the first- and second-generation antihistamines? First generations pass the blood-brain barrier and may cause sedation (reduce ACh release). Second generations have less sedation because they do not traverse the BBB as well.
Names of the first-generation antihistamines (IMPORTANT) Diphenhydramine, hydroxyzine, promethazine, doxylamine, chlorpheniramine, meclizine, dimenhydrinate, diphenhydramine, promethazine
Names of the second-generation antihistamines (IMPORTANT) Terfenadine, fexofenadine, loratadine, desloratadine, cetirizine, levocetirizine
Mechanism of the decongestants Alpha-adrenergic agonists, which constrict mucosal vessels
Names of the decongestants Pseudoephedrine, phenylephrine, oxymetazoline, naphazoline, tetrahydroxoline
Mechanism of guaifenesein Increases respiratory tract fluid secretions and helps loosen phlegm/bronchial secretions
Important Pulm Facts
ARDS criteria (1) Acute onset, (2) PaO2/FiO2 < 200mmHg, (3) bilateral infiltrates, (4) no evidence of heart failure (PCWP/pulmonary capillary wedge pressure < 18).
Major diagnostic feature of COPD FEV1/FVC < 70%
Chronic bronchitis Daily sputum production for at least 3 months a year for 2 consecutive years.
What are the important numbers when considering the initiation of oxygen therapy? PaO2 < 55mmHg, O2 saturation < 88%, hematocrit > 55%
What is the role of D-dimer in pulmonary embolism management? D-dimer helps RULE OUT PE if there is low suspicion. Do NOT test for this if there is high suspicion of PE.
When would an IVC filter be used in PE management? Used to prevent transmission of thromboembolic material from reaching the lung, typically when anticoagulation is contraindicated.
Treatment in PE Immediate anticoagulation (heparin-related drugs). Remember that you must bridge to warfarin from heparin, so you would NOT begin with warfarin alone.
Pages linking here
(main versions and versions by same user)