PBL #6 - Asthma/PE Flashcards
1
Q
What are common clinical presentations of asthma?
A
- expiratory wheezing
- dyspnea
- coughing
- Symptoms may be worse at night, and patients typically awake in the early morning hours
- nonproductive cough (cough-variant asthma)
2
Q
What are common clinical presentations of venous thromboembolism?
A
- Unilateral lower extremity swelling
- History of Risk factors:
- Hospitalization with confinement to bed for > 3 days
- Surgery or general anesthesia in last 3 months
- Trauma in last 3 months
- Pregnancy/recent childbirth
- Oral contraceptives (estrogen)
- Travel for more than 4 hours
3
Q
What are common clinical presentations of pulmonary emboli?
A
- Sudden onset chest pain that is worse with inspiration, dyspnea, SOB, tachycardia
- History of Risk factors:
- Hospitalization with confinement to bed for > 3 days
- Surgery or general anesthesia in last 3 months
- Trauma in last 3 months
- Pregnancy/recent childbirth
- Oral contraceptives (estrogen)
- Travel for more than 4 hours
4
Q
What is the PERC Rule or Pulmonary Embolism Rule-out Criteria?
A
- A “rule-out” tool and ALL variables must receive a ‘no’ to be negative.
- Ask the questions: Age>50, HR > 100, O2 stat on room air <95%, prior history of venous thromboemolism, trauma/surgery within 4 weeks, hemoptysis, exogenous estrogen, unilateral leg swelling?
- Pretest probability is < 1% if all are answered as no.
- Sensitivity 97%
- Specificity 23%
5
Q
Diphenhydramine:
- MOA
- Relate drug distribution to physiologic effects
A
- H1 antagonist (1st gen)
- PK: crosses blood-brain barrier → can cause drowsiness
6
Q
Chlorpheniramine:
- MOA
- Relate drug distribution to physiologic effects
- Side effects
A
- MOA: H1 antagonist (1st gen)
- PK: crosses blood-brain barrier
- **1st generation H1 antagonists also have some anti-muscarinic effects→ drying of secretions, GI disturbances, etc.
7
Q
Fexofenadine:
- MOA
- Relate drug distribution to physiologic effects
A
- MOA: H1 antagonist (2nd gen)
- PK: substrate for P-glycoprotein, actively pumped out of blood-brain barrier → less drowsiness
8
Q
Cetirizine:
- MOA
- Relate drug distribution to physiologic effects
A
- MOA: H1 antagonist (2nd gen)
- PK: substrate for P-glycoprotein, actively pumped out of blood-brain barrier (less drowsiness)
9
Q
Loratadine:
- MOA
- Relate drug distribution to physiologic effects
A
- MOA: H1 antagonist (2nd gen)
- PK: substrate for P-glycoprotein, actively pumped out of blood-brain barrier (less drowsiness)
10
Q
Theophylline
- Class
- MOA
- Relate drug distribution to physiologic effects
- Toxicities
A
- Class: Methylxanthine (caffeine is also a member of this class)
- MOA: Controversial. May be an adenosine antagonist. In high doses it’s a phosphodiesterase inhibitor, increases cAMP → AMP. This may cause bronchodilation.
- PK: Very narrow therapeutic index
- Tox: Arrhythmias, nervousness, GI bleeding, tremors, insomnia
11
Q
Cromolyn sodium:
- Class
- MOA
- Relate drug distribution to physiologic effects
- Toxicities
A
- MOA: (may) block Ca2+ receptors in mast cells → no Ca2+ release into cytoplasm → no degranulation of histamine (according to Dynamed)
- (Dr. Trachte mentioned it might be stabilizing K+ channels?)
12
Q
Epinephrine:
- Class
- MOA
- Relate drug distribution to physiologic effects
- Toxicities
A
- Class: Nonselective adrenoceptor agonist
- MOA: beta-1, beta-2, alpha-1 agonist
- Route: inhalant or subcu
- Tox: Because of beta-1 action, cardiac effects include tachycardia, arrhythmias, angina exacerbation
13
Q
Albuterol:
- Class
- MOA
- Relate drug distribution to physiologic effects
- Toxicities
A
- Class: Short-acting beta-2 adrenoceptor agonist (SABA)
- MOA: beta-2 agonist
- Important to not overuse beta agonists because tolerance can develop
- Overuse of beta agonist causes downregulation of the body’s beta receptors
- Tox: Skeletal muscle tremor
14
Q
Salmeterol:
- Class
- MOA
- Toxicities
A
- Class: Long acting beta-2 adrenoceptor agonist
- MOA: beta-2 agonist, slower onset and longer duration than SABAs
- Tox: overuse can lead to tolerance, downregulation of systemic beta receptors. Skeletal muscle tremor.
15
Q
Zileuton
- Class
- MOA
- Toxicities
A
- Class: Leukotriene receptor antagonist
- MOA: 5-lipoxygenase inhibitor, prevents leukotriene synthesis, less leukotriene B4
- Side effect: hepatotoxicity
16
Q
Zafirlukast
- Class
- MOA
A
- Class: Leukotriene Receptor Antagonist
- MOA: blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors
17
Q
Montelukast:
- Class
- MOA:
A
- Class: leukotriene receptor antagonist
- MOA: block cys-LT1-receptors
18
Q
Prednisone:
- Class
- MOA
A
- Class: Corticosteroid.
- MOA: transcriptionally induces lipocortin to inhibit PLA2; thus inhibiting synthesis of cytokines, especially NF-kappaB.
- An important mechanism is recruitment of HDAC2 to the inflammatory gene complex, which reverses the histone acetylation associated with increased gene transcription of Beta 2 receptors.
19
Q
Triamcinolone:
- Class
- MOA
A
- Class: Glucocorticoid
- MOA: Transcriptionally induces lipocortin to inhibit PLA2; thus Inhibiting synthesis of cytokines, especially NF-kappaB
20
Q
Flunisolide:
- Class
- MOA
A
- Class: Glucocorticoid receptor agonist
- MOA: binds to cytoplasmic glucocorticoid receptors → initiates the transcription of glucocorticoid-responsive genes such as lipocortins.
- Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes
21
Q
What are the NINE Glucocorticoids that can be used in the treatment of asthma?
A
- Prednisone
- Methylprednisolone
- Dexamethasone
- Betamethasone
- Beclamethasone
- Budesonide
- Triamcinolone
- Flunisolide
- Fluticasone
22
Q
What is the MOA of Omalizumab?
A
- Binds specifically to circulating IgE and blocks its binding with the high-affinity IgE receptor (FcεRI) on the surface of mast cells and basophils.
- Reduces the number of FcεRI receptors on basophils and submucosal cells in atopic patients
23
Q
What is the MOA of Formoterol?
A
Direct acting beta-2 selective agonist;
slow onset of action but long duration of action
24
Q
What is the MOA of Pirbuterol?
A
- MOA: Short acting beta agonist
- Uses: acute bronchospasm attack
- Duration of action is 4 hrs or less
- Just like albuterol
25
Why don't we treat asthma with antihistamines?
* Giving histamine will directly mimic asthma
* BUT histamine is NOT the cause of asthma, because antihistamines are **ineffective** in treating it.
* Leukotrienes are the cause.
26
What are the first generation antihistamines?
* Diphenhydramine (Benadryl)
* Meclizine
* Chlorphenamine
27
What are the second generation antihistamines?
* Cetirizine
* Loratidine
* Fexofenadine
28
How should you treat Step 1 - Intermittent asthma?
A controller medication is not indicated. The reliever medication is a short-acting beta-agonist (SABA) as needed for symptoms.
29
How should you treat Step 2 - Mild persistent asthma?
The preferred controller medication is a low-dose inhaled corticosteroid. Alternatives include sodium cromolyn, nedocromil, or a leukotriene receptor antagonist (LTRA).
30
How should you treat Step 3 - Moderate persistent asthma?
* The preferred controller medication is either:
* a low-dose inhaled corticosteroid plus a long-acting beta-agonist (LABA) (combination medication preferred choice to improve compliance)
* or an inhaled medium-dose corticosteroid.
* Alternatives include an inhaled low-dose ICS plus either a leukotriene receptor antagonist, theophylline, or zileuton (Zyflo).
31
How should you treat Step 4 - Moderate-to-severe persistent asthma?
The preferred controller medication is an inhaled medium-dose corticosteroid plus a leukotriene receptor antagonist (combination therapy). Alternatives include an inhaled medium-dose corticosteroid plus either a leukotriene receptor antagonist, theophylline, or zileuton.
32
How should you treat Step 5 - Severe persistent asthma?
The preferred controller medication is an inhaled high-dose corticosteroid plus a leukotriene receptor antagonist.
Consider omalizumab for patients who have allergies.
33
What nonpharmacologic interventions can help manage asthma?
* **Breathing exercises**
* Buteyko technique: aims to correct breathing patterns by reducing hyperventilation and thus resetting CO2 levels. Involves periods of breath holding interspersed with periods of shallow breathing, accompanied by physical activities to further increase the buildup of CO2.
* Papworth Method of integrated breathing and relaxation techniques - focuses on dysfunctional breathing including hyperventilation and hyperinflation common in patients with asthma and reducing anxiety associated with breathlessness and wheezing.
* **Yoga**
* **Activity**: aerobic training may reduce symptom frequency and improve asthma-related quality of life in adults with asthma. It is also associated with reduced frequency of exacerbation.
34
What is the effect of a competitive antagonist on a dose response curve?
* Competitive antagonist:
* bind to the receptor in a reversible way without activating the effector system for that receptor
* will shift an agonism dose-response curve to the right
* same maximal effect is reached
35
What is the effect of an inverse agonist on a dose response curve?
* Inverse agonist:
* binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist
* decreases the activity below the basal level
36
What is the mechanism of aspirin-induced hypersensitivity asthma?
Decreased prostaglandin E2 (PGE2) synthesis → Overproduction of Leukotrienes at baseline (LTC4 in particular)→ bronchoconstriction, mucus secretion, nasal mucosal swelling, and airway edema, and also attract eosinophils into the airways → + COX inhibitors (aspirin, NSAIDs) → more Leukotriene pathway → exacerbates symptoms → Boom, you got the triad
37
What is the triad of symptoms in Aspirin-exacerbated asthma or Aspirin-Exacerbated Respiratory Disease (AERD)?
1. asthma
2. aspirin induced bronchospasms
3. nasal polyps
38
What is the impact of a V/Q mismatch on gas exchange?
* V/Q = the ratio of the amount of air reaching the alveoli to the amount of blood reaching the alveoli
* "V" = ventilation: air that reaches the alveoli
* "Q" = perfusion: blood that reaches the alveoli
* In PE:
* blood circulation is impaired by an embolus
* Ventilation is wasted, as it fails to oxygenate any blood
* high V/Q ratio decreases PACO2 and increases PAO2
39
What does "Allelic heterogeneity" mean?
Different mutations in the same locus produce the same phenotype.
40
What is the value of treating allergic rhinitis as appropriate for asthma management?
* Locally applied (topical) corticosteroid sprays given to improve rhinitis symptoms can also improve symptoms of asthma and reduce the underlying hyperreactivity (the heightened sensitivity of the lungs to inhaled stimuli)
* Things that may help with both:
* corticosteroid nasal sprays
* Antihistamines
* antihistamine plus pseudoephedrine
* Antibiotic therapy in sinus infection
* sinus surgery
41
What is the MOA of Heparin?
Cofactor for the activation of antithrombin, decreases activity of thrombin and factor Xa.
Will increase your PTT. Reverse effects with Protamine.
42
What is the MOA of LMW Heparin (enoxaparin, dalteparin)?
Similar to Heparin but act more on factor Xa. Have longer half-life and not as easily reversible.
43
What is the MOA of Warfarin?
Interferes with the normal synthesis and gamma-carboxylation of Vitamin K-dependant clotting factors II, VII, IX, and X and proteins C and S.
Has effect on SEXtrinsic pathway thus increasing you PT.
\*\*\*Remember to bridge with heparin because it will inhibit protein C first, making you more susceptible to clotting.
44
What are the Direct factor Xa inhibitor anticoagulants that we need to know?
* Apixaban
* Rivaroxaban
* anything with an "xa" in the name!
45
What are the Direct thrombin inhibitors that we need to know?
* Bivalirudin
* Argatroban
* Dabigatran
