Ch. 7 Pharmacology & Therapeutics Flashcards
How long does cat allergen remain in the home after cat removal?
4-6 months
Indications for AIT?
allergic rhinitis/conjunctivitis, allergic asthma, atopic dermatitis with aeroallergen sensitization, venom hypersensitivity
With regard to asthma, AIT improves what?
bronchial hyper responsiveness only, there is NO effect on pulmonary functions tests
With regard to AR, AIT improves what?
symptom scores, quality of life, and medication reduction
What happens to allergen-specific IgE in the first few months of AIT?
allergen-specific IgE increases (decreases later).
What immunologic changes are expected with completion of AIT?
Increase: IgG4, IgA in respiratory secretions, Tregs, CD8+ T cells, Th1 cytokines (IFNgamma, IL-12), Th1/Th2 ratio, IFNg/IL-4 ratio
Decrease: allergen-specific IgE (initially increases), early-late response to allergen, FcERII (CD23 - low affinity receptor), basophil hyperactivity, recruitment of eos/baso/mast cells, allergen-specific lymphocyte proliferation
What are the standardized extracts?
cat, dust mite, grass (northern grasses and Bermuda), ragweed
What color vial is 1:10,000 vol/vol (1:1,000,000 w/v)
silver
What color vial is 1:1000 vol/vol (1:100,000 w/v)
green
What color vial is 1:100 vol/vol (1:10,000 w/v)
blue
What color vial is 1:10 vol/vol (1:1000 w/v)
yellow
What color vial is 1:1 vol/vol (1:100 w/v)
red (maintenance)
Name the 7 northern grasses
timothy, orchard, kentucky blue, perennial rye, sweet vernal, red top, meadow fescue
Which two southern grasses cross-react?
bahia and johnson
What does glycerin in allergen extracts do?
inhibitor of proteolytic activity that can be irritating/painful (NOT associated with local reactions)
What does phenol in allergen extracts do?
antibacterial
Which allergen extracts contains proteolytic enzymes that degrade pollen?
mold and cockroach
Note: can mix mold and cockroach together
T or F, can you mix dust mite (in >10% glycerin) with cockroach and mold?
T
Note: Can also mix dust mite with pollen, dog/cat
Which venoms can be mixed together?
Mixed vespid (yellow jacket, white hornet, yellow hornet)
What is the maintenance dose for a single venom?
100ug
What is the maintenance dose for mixed vespid
300ug
What is the effective BAU for cat allergen?
1000-4000 BAU
What is the effective dose for dog allergen Can f 1?
15ug Can F 1
What is the effective AU for dust mites (Der f1, Der p1)?
500-2000 AU
What is the effective BAU for Bermuda?
300-1500 BAU
What is the effective BAU for grass
1000-4000 BAU
What is the effective dose of Amb a1 and AU?
6-12 ug Amb a 1; 1000-4000 AU
In general, what is the range of the effective maintenance dose for most inhalant allergens?
5-20 ug per 0.5mL maintenance dose
What are the 5 grasses in the SLIT tablet and when do you start?
timothy, orchard, kentucky blue, perennial rye, sweet vernal; 16 weeks before grass season
(age 10-65)
What is the grass pollen in the single SLIT tablet and when do you start?
timothy grass; start 12 weeks before grass season
age 5-65
What allergen is in the ragweed tablet and when do you start?
Amb a 1; 12 weeks before ragweed season
age 18-65
Which anti-histamines need dose adjustment if there is hepatic impairment, i.e. exclusively cleared by the liver?
1st generation: diphenhydramine, doxepin, hydroxyzine
2nd generation: loratadine
Which anti-histamines need dose adjustment for renal impairment, i.e. exclusively cleared by the kidney?
fexofenadine
Which anti-histamines are both cleared by the kidney and liver and need adjustment for renal and hepatic impairment?
cetirizine, desloratadine, levocetirizine
Which anti-histamines are pregnancy class B?
1st gen: chlorpheniramine, diphehydramine
2nd gen: cetirizine, levocetirizine, loratadine
topical: emedastine
Adverse effect of dry mouth and urinary retention are due to H1 antihistamine effects on which receptor?
muscarinic / cholinergic receptors
Cyproheptadine can cause increased appetite due to its effect on which receptor?
serotonin receptor
What is the mechanism of action of albuterol?
binds to B2 receptor (GPCR), activates adenylate cyclase, increases cAMP, activating PKA, leading to phosphorylation and muscle relaxation (bronchodilation)
What accounts for salmeterols longer/slower onset of action compared to formoterol?
greater lipophilicity
Increasing the bulk of the B agonist side chain results in what pharmacologic property?
increased selectivity for B2 receptor, prolonged duration of action, and protects from catceholamine-O-methyltransferase (COMT) degradation
Increasing the size of the terminal amino group of B agonists results in?
protection from degradation by monamine oxidase
What genetic polymorphism has been shown to result in B2 agonist receptor down regulation resulting in resistance to smooth-muscle relaxing effect of B2 agonists?
B16 Arg/Arg homozygosity
Name the 5 non-selective B blockers
propanolol, timolol, pindolol, nadolol, labetalol (also blocks alpha 1)
Note: associated with blunted response to B2 agonists
Name the 2 cardioselective B blockers
metoprolol and atenolol
Note: >20 times more affinity for B1 receptors
What are the effects of leukotriene antagonists in AERD?
- Improves FEV1
- Less need for rescue B agonist
- decrease in asthma exacerbations
Which leukotriene antagonist can have liver toxicity and can interact with warfarin leading to increased PT time?
zafirlukast Note: Pregnancy class B
Which leukotriene antagonist can increase ALT (liver transaminases), inhibits CYP1A2, and affects the levels of theophylline, warfarin, and propranolol?
Zileuton (5-LO inhibitor) Note: Pregnancy class C
Antileukotriene therapy has been associated with what disease due to unmasking with corticosteroid taper?
eosinophilic granulomatosis with polyangiitis (EGPA aka Churg-Strauss)
What is the function of the M2 (muscarinic) receptor?
inhibitory receptor on parasympathetic nerves, decreases Ach release
Which muscarinic receptor is the primary mediator of smooth muscle contraction in human airways?
M3 receptor - increases intracellular Ca, causing bronchoconstriction
Ipratropium is recommended in the 2007 EPR3 to be used in combination with B agonists in mod-severe asthma exacerbations because it has been shown to decrease…?
hospitalization rates
Ipratropium blocks M2 and M3 receptors with equal affinity, blocking of M2 receptors can lead to?
bronchoconstriction (blocking M2 receptors leads to increase Ach release, thus why you can see paradoxical bronchoconstriction with ipratropium)
Theophylline is metabolized by cytochrome P450, what medications can INCREASE its serum levels?
macrolide antibiotics, cimetidine, cipro, verapamil, zileuton, allopurinol
Theophylline is metabolized by cytochrome P450, what medications can DECREASE its serum levels?
carbamazepine, phenobarbital, phenytoin, rifampin, ethanol
Adverse effects of theophylline are seen at plasma levels greater than…?
> 20 mg/L
Steroids cause what type of cataracts?
sub capsular posterior cataracts
Which phase of antigen challenge do steroids inhibit?
late phase only
Relative anti-inflammatory potency of ICS
mometasone > fluticasone > budesonide = beclomethasone
Where does omalizumab bind?
CH3 domain (Fc portion) of IgE
What happens to total and free IgE with omalizumab?
free IgE decreases, total IgE increases
What is the difference between the FcERI receptors on mast cells and basophils compared to other cells?
FcERI on mast cells & basophils has 4 chains (one alpha, one beta, two gamma chains)
FcERI on other cells has 3 chains: NO BETA CHAIN (one alpha, two gamma chains)
Note: IgE binds to alpha chain
What infection has been reported in patients taking mepolizumab?
herpes zoster (shingles)
What is the dose for omalizumab in asthma?
based on weight and total IgE (between 30 - 700 IU/ml)
What is the dose for omalizumab in CIU?
150mg or 300mg subq every 4 weeks
What is the dose for mepolizumab in asthma?
100mg subq every 4 weeks
blood eos>150 cells/uL, or 300 in last 12 months
What is the dose for reslizumab in asthma?
3mg/kg IV every 4 weeks
blood eos >400
What is the most common adverse event with reslizumab?
oropharyngeal pain
Medications that decrease glucocorticoid metabolism
OCPs, macrolide antibiotics, ketoconazole
What is the incidence of anaphylaxis with omalizumab?
0.20%
Cyclosporine binds to…?
cyclophilin (immunophilin)
Tacrolimus binds to…?
FK-binding protein (immunophilin)
Which interferon is approved for clinical use for CGD and malignant osteopetrosis?
IFNgamma-1b
Which TNF inhibitor binds both TNFa and TNFb?
etanercept (enbrel)
all others bind TNFa only (infliximab, adalimumab, certolizumab pegol, golimumab)
A screen for which infectious organism is needed prior to starting TNF inhibitors and annually while on therapy?
mycobacterium tuberculosis (PPD test)
COX-2 inhibitors
celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib, valdecoxib
AERD patients typically tolerate acetaminophen at what dose?
<1000 mg
COX-1 inhibition results in decreased production of?
PGE2 - inhibitor of 5-LO
When should leukotriene inhibitors be started prior to aspiring challenge/desensitization for AERD?
1 week prior
At what dose do reactions to aspirin desensitization typically occur?
40mg
In children or infant CPR, if there are 2 rescuers, what is the compression: breath ratio?
15:2
Note: 30:2 for adults or child with 1 rescuer
Patient is on b-blocker, first drug given for anaphylaxis?
Epinephrine
0.01 mg/kg SC/IM of 1:1000 dilution; 0.01 mg/kg IV of 1:10,000 dilution
Name the live vaccines
MMR, Nasal flu, Oral polio, Rotavirus, Smallpox (Vaccinia), Varicella, Zoster
Live vaccines must be separated by how many days if not given the same day?
28 days
If a patient does not have a functioning spleen, how should you administer PCV13 and Menactra?
administration should be separated by 4 weeks
After IVIG or packed RBCs, how long to wait before giving live vaccine?
> 3 months for live vaccine
After packed RBCs, how long to wait before giving non-live vaccine? After IVIG?
6 months after RBC, 8 months after IVIG
If a live vaccine is given, how long to wait to give IVIG?
2 weeks
exception: no issue with pavlizumab and live vaccine
Which vaccines contain egg?
Influenza, Yellow fever
What are the gelatin containing vaccines?
MMR. Varicella-zoster, rabies, and yellow fever
Which vaccine causes a delayed urticaria and angioedema?
Japanese encephalitis virus (JEV) vaccine
Which vaccine can cause eczema vaccinatum?
smallpox vaccine
If not given the same day, TB skin test and MMR should be spaced by?
4 weeks
Contraindications to live vaccines
pregnancy, immunosuppression
Contraindication to vaccination
severe allergic reaction (anaphylaxis) to vaccine, encephalopathy <7 days after pertussis vaccine, hx of Guillain-Barre
Indications for tympanostomy tubes
OME with structural damage Recurrent OME (3 or more in 6 months, 4 or more in 1 year) Persistent OME (3 months bilateral, 6 months unilateral) Hearing loss
Type IVa - cytokines, cells involved, skin findings
Th1 (IFNg), monocyte, eczema
Type IVb - cytokines, cells involved, skin findings
Th2 (IL-4, IL-5), eosinophil, maculopapular or bullous
Type IVc - cytokines, cells involved, skin findings
CTL (perforin, granzyme), CD4 and CD8, maculopapular/bullous/pustular
Type IVd -cytokines, cells involved, skin findings
T lymphocytes (IL-8), PMNs, pustular
Which MHC marker is associated with abacavir reaction?
HLA-B*5701
MHC marker associated with carbamazepine reaction?
HLA-B*1502
What is the major determinant for Penicillin?
benzylpenicilloyl polylysine (Prepen)
What is the NPV of PCN skin testing?
97%
Aztreonam cross reacts with what B-lactam?
ceftazidime
IgE mediated reactions to sulfa antibiotics are due to which determinant?
N4-sulfonamidoyl
Risks for radio contrast adverse reactions?
female, asthma/atopy, CV disease, prior hx of reaction
Treatment for SJS/TEN?
supportive, IVIG may be helpful.
Note that steroids are contraindicated in TEN
Vancomycin is associated with what skin condition?
linear IgA bullous dermatitis
Mechanism of HIT (heparin induced thrombocytopenia)?
IgG to heparin platelet factor 4 immune complexes
Most common drug causing serum sickness in kids?
cefaclor
autoAb in drug induced CUTANEOUS lupus? Most common drugs to cause?
anti-Ro (SSA) or anti-La (SSB);
HCTZ, CCB, ACE-I, antifungals
AutoAb in drug induced lupus (systemic)? Common offending agents?
antihistone;
procainamide, hydralazine, phenytoin, isoniazid
