Term
|
Definition
| chest tightness, wheezing, dyspnea and cough |
|
|
Term
| 2 COMPONENTS OF HYPERRESPONSIVENESS & definitions |
|
Definition
1. Hypersensitivity: A normal response to abnormally low levels of stimulation. (i.e. airways of asthmatics constrict too readily)
2. Hyperreactivity: An exaggerated response to normal or high levels of stimulation. (i.e. the airways respond too vigorously) |
|
|
Term
| Why give asthmatic drugs using aerosol delivery? |
|
Definition
| achieve high local concentrations of the drug in the lung with minimal amount of drug being delivered systemically (dec systemic side effects) |
|
|
Term
| Possible effects of B1 agonists? |
|
Definition
| INC heart rate, contractility of heart, renin release, lipolysis |
|
|
Term
| Possible effects of B2 agonists? |
|
Definition
INHIBITS bronchoconstriction
Vasodilation
INC heart rate, contractility, lipolysis, insulin release
DEC uterine tone |
|
|
Term
| What does stimulating B2 receptors on cholinergic terminals do? |
|
Definition
DEC ACh
This is good b/c during resting state, parasympathetics cause BRONCHOCONSTRICTION. So.. dec ACh causes dec bronchoconstriction --> inc bronchodilation! |
|
|
Term
| Do you use B2 agonists in prophylactically or in an SOS situation? |
|
Definition
SOS!
Prophy --> tachyphylaxis (a decrease in the response to a drug due to previous exposure to that drug) |
|
|
Term
| Problem with HIGH dose B2 agonists? |
|
Definition
| Lose selectivity... start to work on B1's also! |
|
|
Term
| Main mechanisms of B2 agonists |
|
Definition
Goal: Keep bronchioles from contracting
1. Inactivates MLCK (myosin can't be P'd)
2. Activates Ca2+ pumps (sequesters all Ca2+)
3. Activates Ca2+-sensitive K+ channels --> Hyperpolarization and relaxation |
|
|
Term
| Effect of B2 agonists on mast cells |
|
Definition
| Inhibit degranulation --> DEC histamine |
|
|
Term
| Name the Short Acting Beta Agonists (SABA) -- B2 Selective |
|
Definition
Albuterol
Levalbuterol
Metaproterenol
(Leave Me Alone) |
|
|
Term
|
Definition
|
|
Term
| Which SABA has a pediatric formulation available? |
|
Definition
|
|
Term
|
Definition
Nebulized Mg2+ inc bronchodilation
HOW???
-Keeps cells from moving Ca2+ across membranes
-Dec depolarizing action of ACh (remember.. PS=bronchoconstriction)
-stabilizes mast cells and T-lymphocytes |
|
|
Term
| Which SABA can delay labor? |
|
Definition
Albuterol
(I would think all B2 agonists could potentially do this since one of the actions of B2 = dec uterine tone) |
|
|
Term
| Most selective of SABAs? Why? |
|
Definition
Levabuterol
Tighter binding to B2 receptors |
|
|
Term
| Least selective of SABAs? |
|
Definition
Metaproterenol
Expect more cardiac stimulation (B1) |
|
|
Term
| Name the Long Acting Beta Agonists (LABA) -- B2 Selective |
|
Definition
Formoterol
Arformoterol
Salmeterol
Indacaterol
(FArSI) |
|
|
Term
| Which LABA has a RAPID ONSET??? |
|
Definition
|
|
Term
| Which LABA is NOT for acute attacks? |
|
Definition
Salmeterol
20 min onset.. too slow |
|
|
Term
| Which LABA is metabolized by CYP3A4? |
|
Definition
Salmeterol
CYP3A4 inhibitors --> inc risk for CV SE |
|
|
Term
| General warning for ALL B2 Agonists (SABAs & LABAs) |
|
Definition
Paradoxical bronchospasm
Unknown cause |
|
|
Term
| _______ MUST be used with an inhaled corticosteroid/glucocorticoid. Why? |
|
Definition
LABAs
Will inc the risk of asthma episodes/asthma-related death w/o the concomitant use of ICS
ALSO glucocorticoids INC the # of B2 receptors (I think this means that if there are more B2R's then the drug's likelihood of binding to B1R's dec..) |
|
|
Term
|
Definition
Palpitations, tachycardia, BP changes
Tremors
Muscle cramps
Hypokalemia |
|
|
Term
| Why do you get hypokalemia w/ B agonists? |
|
Definition
| B2 stimulation drives K+ into muscles in exchanges for Na2+ --> low K+ plasma levels |
|
|
Term
| Name the inhaled corticosteroids |
|
Definition
TRIAMCINOLONE (Azmacort®)
CICLESONIDE (Alvesco®)
BECLOMETHASONE (Qvar®)
MOMETASONE (Asmanex®)
BUDESONIDE (Pulmicort®)
FLUTICASONE (Flovent Diskus®) |
|
|
Term
| Why do we give corticosteroids to ppl with asthma? |
|
Definition
|
|
Term
|
Definition
Bind to glucocorticoid reponse elements of DNA --> regulates transcription!
1. DEC genes for pro-inflam cytokines
2. INC annexin-1 (inhibits PLA2 --> dec arachidonic acid)
3. Induces apoptosis of Th2 lymphyocytes
4. DRC binds and inactivates AP-1 and NFKB (activate during inflam) |
|
|
Term
| Which inhaled corticosteroid could you give to a 3 yo w/ asthma? |
|
Definition
Budesonide (12 mo+)
TRIAMCINOLONE (doesn't say)
CICLESONIDE (12 yo+)
BECLOMETHASONE (5 yo+)
MOMETASONE (4 yo+)
FLUTICASONE (4 yo+) |
|
|
Term
| Effect of liver problems for someone on Budesonide? |
|
Definition
| Cleared by liver --> build up, potentially double the systemic availabilty |
|
|
Term
| HIGHLY protein bound inhaled corticosteroids? |
|
Definition
Mometasone (98-99%)
Ciclesonide (active form >99%)
Triamcinolone -- only moderately bound (67%) |
|
|
Term
| What makes ciclesonide a relatively safer drug? |
|
Definition
The fact that the drug is so extensively bound to the plasma proteins that only a very small fraction (<1%) would be available in the unbound state. Only the unbound form is pharmacologically active.
(Would this apply to Mometasone too..? It's 98-99% PB) |
|
|
Term
| All the drugs in this lecture metabolized by CYP3A4 |
|
Definition
Salmeterol - LABA
Mometasone - ICS
Zileuton - Leukotriene synthesis inhibitor |
|
|
Term
|
Definition
1. Suppression of HPA
2. Oral candidiasis
3. Dec bone mineral density
4. Reduction of growth velocity in kids |
|
|
Term
| Name the oral corticosteroids |
|
Definition
|
|
Term
| How are prednisone and prednisolone related? |
|
Definition
Prednisone = pro-drug
Prednisolone = active form |
|
|
Term
| What/where converts prednisone to prednisolone? |
|
Definition
| 11β- hydroxysteroid dehydrogenase I enzyme in the liver |
|
|
Term
| Which corticosteroid is safe to give to pregnant women? |
|
Definition
Prednisone
because the fetal barrier converts the prednisolone back to inactive prednisone |
|
|
Term
|
Definition
| DEATHS have occurred when switching from chronic systemic steroids to inhalationals! If tx > 7 days, wean systemic drug gradually. |
|
|
Term
| SE's oral corticosteroids have that inhaled don't? |
|
Definition
1.Osteonecrosis – femoral head most often, can involve hip, shoulder, knee. Early Sx include joint pain, stiffness.
2.↑’d opportunistic infections
3.Mental disturbances, weight gain, Cushing’s like features (moon facies and buffalo hump). |
|
|
Term
|
Definition
Theophylline
Aminophylline |
|
|
Term
|
Definition
1. Inhibits PDE III & IV --> inc cAMP --> bronchodilation (IV --> anti-inflam by inhibiting T lympho and eosinophils)
2. Adenosine R antagonist -- adenosine normally bronchoconstricts and releases histamine
3. Activates histone deacetylases -- dec transcription of pro-inflam genes |
|
|
Term
| Besides methylxanthines, what other drug inhibits PDE IV? |
|
Definition
Roflumilast
SELECTIVE inhibitor |
|
|
Term
| What disease(s) can you give methylxanthines? |
|
Definition
Chronic airflow obstruction diseases
(Chronic asthma, emphysema, chronic bronchitis) |
|
|
Term
| How could low albumin --> theophylline toxicity? |
|
Definition
40% binds to albumin -- if someone has LOW albumin, then you have more FREE drug in the blood
Pt can show toxicity even if drug concentrations (bound+unbound) are within therapeutic range
ALSO, unbound drug could be in therapeutic range even if TOTAL drug conc is below therapeutic range |
|
|
Term
| When theophylline is above therapeutic conc, why is the elimination prolonged? |
|
Definition
| it saturates its metabolic enzymes and follows zero-order kinetics |
|
|
Term
| Why does CHF and liver dysfunction lead to inc risk of theophylline toxicity? |
|
Definition
1. CHF - Dec O2 --> can't metabolize drug b/c metabolism involves oxidation
2. Metabolized in the liver by P450 isoenzyme CYP3A |
|
|
Term
| Types of drug-drug interactions theophylline is susceptible to? |
|
Definition
Drugs that inhibit (cimetidine, azole antifungals) or induce (barbiturates, phenytoin) P450 levels
(It's metabolized by P450 isoenzyme CYP3A) |
|
|
Term
| Anhydrous v. dihydrate forms of aminophylline |
|
Definition
Anhydrous = 86% theophylline
Dihydrate = 79% theophylline |
|
|
Term
|
Definition
1. Arrhythmias, convulsions, sudden death
2. NV, tremors, HA, tachycardia
3. Drug drug interactions |
|
|
Term
| Name the anticholinergic drugs from this lecture |
|
Definition
|
|
Term
| MOA of anticholinergic drugs? |
|
Definition
Blocks M3R's so ACh can't bind
(Remember.. PS at rest state causes bronchoconstriction) |
|
|
Term
| Which anticholinergic drug is more selective at the MR's? |
|
Definition
Tiotropium
Ipratropium poorly discriminates b/t the MR's |
|
|
Term
| What diseases are the anticholinergic drugs used for? |
|
Definition
Treats bronchospasms!
Ipratropium
COPD, chronic bronchitis, emphysema
Tiotropium
COPD |
|
|
Term
| Longer acting of the 2 anticholinergic drugs? |
|
Definition
|
|
Term
| How does Ipratropium compare to B2 agonists in terms of bronchodilation in asthmatics? |
|
Definition
| Ipratropium produces slower & less intense bronchodilation |
|
|
Term
| Of the drugs from this lecture, which one do you have to be careful when giving to ppl w/ narrow angle glaucoma? |
|
Definition
Ipratropium (anticholinergic drug)
Relaxation of ciliary muscle --> INC intra-ocular pressure in the eye |
|
|
Term
| What is a potential SE for COPD pts using anticholinergic drugs for 1-6 months? |
|
Definition
|
|
Term
| Which anticholinergic drug should you not give to pts w/ renal problems/failure? |
|
Definition
Tiotropium
Renally excreted |
|
|
Term
| Name the leukotriene receptor antagonists |
|
Definition
|
|
Term
| Which groups of drugs ARE NOT to be used for acute asthma attacks? |
|
Definition
Corticosteroids
leukotriene receptor antagonists
Cromolyn sodium (mast cell stabilizer)
(I only listed the ones that were STATED to be not used for acute attacks from the HO) |
|
|
Term
| MOA of leukotriene receptor antagonists? |
|
Definition
Blocks cyteinyl LT-1 receptors
This prevents the following:
plasma exudation
mucus secretion
bronchoconstriction
eosinophil recruitment |
|
|
Term
| Which leukotriene receptor antagonists can you use in 1 yo? |
|
Definition
Montelukast (12 mo+)
Zafirlukast (5 yo+) |
|
|
Term
| What are leukotriene receptor antagonists prescribed for? |
|
Definition
| Prophy and chronic tx of asthma |
|
|
Term
|
Definition
Liver dysfunction --> inc drug levels by 50-60%
**Drugs that induce liver metabolism will also dec montelukast lvls |
|
|
Term
| Don't give Zafirlukast with what drugs from this lecture? |
|
Definition
Salmeterol - LABA
Mometasone - ICS
Zileuton - Leukotriene synthesis inhibitor
Zafirlukast inhibits CYP3A4 (and CYP2C9) and these drugs are metabolized by CYP3A4
ALSO!!! Theophylline dec Zafirlukast lvls by 30% |
|
|
Term
| Precautions when administering leukotriene receptor antagonists? |
|
Definition
| Administered orally.. high fat/protein meal can dec bioavailability |
|
|
Term
| What type of drug is Zileuton? |
|
Definition
| leukotriene synthesis inhibitor |
|
|
Term
|
Definition
Inhibits 5-lipoxygenase
NOT 5-lipoxygenase activating protein |
|
|
Term
| Precautions when administering Zileuton? |
|
Definition
Given orally
Cmax and AUC ↑ in presence of food with delay in Tmax |
|
|
Term
| Drug interactions of Zileuton? |
|
Definition
•Can significantly alter (double) theophylline drug concentration when co-administered.
•Co-administration could significantly ↑warfarin prothrombin times.
•Can double systemic exposure of propranolol → ↑ β-blocker activity |
|
|
Term
| FDA warning about drugs that affect leukotriene synthesis (Zileuton)? |
|
Definition
neuropsychiatric events
(agitation, aggression, insomnia, depression, hallucinations, suicidality et al.) |
|
|
Term
|
Definition
Cromolyn Sodium
Nedocromil |
|
|
Term
| MOA of mast cell stabilizers |
|
Definition
Keeps histamine from being released
Inhibits Cl- transport required for Ca2+-induced histamine released |
|
|
Term
| Mast cell stabilizers uses |
|
Definition
| Asthma, bronchospasms, allergic rhinitis |
|
|
Term
| Which mast cell stabilizer is for ophthalmic use only? |
|
Definition
|
|
Term
| What type of drug is Omalizumab? |
|
Definition
|
|
Term
|
Definition
recombinant humanized monoclonal antibody targeted against IgE
Binds to the Fc region of IgE so that IgE can't bind to FcεRI of mast cells --> no degranulation --> dec stimulation of TH2 |
|
|
Term
| How is Omalizumab administered? |
|
Definition
| Given SC q 2-4 wks for asthma due to an allergen identified by a (+) skin test |
|
|
Term
| What is Omalizumab used for? |
|
Definition
| allergies and moderate-to-severe persistent asthma |
|
|
Term
| Can you give Omalizumab to a 10 yo? |
|
Definition
|
|
Term
|
Definition
| Risk of acute delayed onset anaphylaxis despite inhibiting cross-linking of IgE. Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue |
|
|
Term
| What's the big deal concerning asthmatics and aspirin? |
|
Definition
1 in 5 are SENSITIVE to aspirin
Inhibiting COX might shift arachidonic acid metabolism from PGs to LTs → exacerbation of asthma symptoms (Remember.. we have all those drugs preventing LTs from doing their job.. they aren't good for ppl w/ asthma) |
|
|
