Asthma Drugs Clinical Pharmacology

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inhaled corticosteroids direct MOA

inhibit (cytokine-induced) production of inflammatory proteins

2.

pharm agents causing

ASA, Beta blockers

3.

physical triggers

cold air, exercise

4.

physiologic triggers (4)

stress, GERD, URI, rhinitis

factors influencing dev/exp - host

genetic, gender, obesity

6.

inflam cells in asthma

mast, eosino/baso/neutrophils, platelets, TH2

7.

mediators

histamine LTE Kinins, endothelin, prosanoids

8.

diagnosis

>12% reversibility or increase in FEV1 of 200c

9.

obstructive pattern

reduced FEV1/FVC ratio w/ albuterol

10.

restrictive pattern

reduced FVC (normal ratio) w/ albuterol

11.

methacholine challenge

bronchoprovocative test; 20% or more decrease in FEV1

12.

Severe asthmatic episode - ABG

pH down paCo2 down pa02down HCO3 way down

1.

5.

13.

sputum

eosinophils, charcot-leyden crystals, inc IgE

14.

chest xray

inc AP diam, dark (translucent) fields, depressed/flat diaphragm

15.

Step 1 - 4; symptom freq

1; 2x per week 3; daily 4; continual

21.

mast cells

filled w/ basophil granules

22.

short acting beta agonists

relax smooth muscle, inc airflow in 30 sec; DOC for attacks

23.

indicates inadequate control

> 1 canister/mth SABA

24.

dosing positive response is

200 ml increase or 12% increase in FEV1

25.

Beta2 agonists SE

tremor heart palps hypokal O2 sat reduction

26.

SABAs - ALPMT (short goats on alp mountains)

Albuterol Levalbuterol Pirbuterol Metaproterenol Terbutaline

27.

dosing levalbuterol (Xopenex) - only R isomer/active

half of racemic albuterol - 0.63 mg, 1.25 mg (3X cost)

28.

LABAs - AFAS

Albuterol ER Formoterol Aformoterol, Salmeterol,

29.

LABA's considerations

not monotherapy; only if cannot be controlled otherwise shortest duration & taper off

30.

LABAs - COPD only

Formoterol Aformoterol

31.

combo LABA & corticosteroids (3)

Symbicort, Dulera, Advair

32.

Symbicort

Formoterol & Budesonide

33.

Advair

Salmeterol & Fluticasone

16.

Zone mgmnt green/yellow/red

patient self monitoring system

34.

Dulera

Formoterol & Mometasone (asthma only)

17.

asthma classifications

allergic, exercise induced, nocturnal

35.

Dulera

18.

non drug treatment, avoid triggers & treat aggravating

allergies, GERD, rhinitis, viral RI

combo LABA & steroid for asthma only

36.

inhaled corticosteroids direct MOA

inhibit cytokine (induced prod of pro-inflamm proteins)

19.

drug types for asthma (6)

beta agonists, corticosteroids, mast cell stabilizers, LTE modifiers, theophylline, anti IgE ab's

37.

inhaled corticosteroids indirect MOA (4)

20.

Beta 2 agonists MOA

G-protein receptors activates adenylyl cyclase/cAMP - > intercellular Ca -> bronchodiliation & mast cell stabilization

alter m-RNA prod suppress inflam produce anti-inflam mediator increase B2 receptors, decrease mucous

38.

mild asthma - once a day inhaled steroid options

budesonide ciclesonide mometasone furoate

39.

corticosteroids SEs

thrush; hypergly adrenal suppress osteoporosis elev WBC

52.

cromolyn (intal) - class nedocromil (tilade)

mast cell stabilizer (no inherent bronchodilation)

53.

cromolyn MOA

blocks Cl channels blocks histamine release from mast cells

54.

cromolyn SE

bad taste; GI

55.

Montelukast (Singulair) class Zafirlukast (Accolate)

LTE receptor antagonists

56.

Zileuton (zyflo) - class

LTE receptor antagonists 5-lipoxygenase inhibitor reduces synthesis

57.

Zileuton (zyflo) interaction

inhibits metabolism of theophylline & warfarin (increases levels)

58.

LTE antagonists - not indicated for

acute attacks

blockade adenosine receptors

59.

Montelukast vs Zafirlukast

Montelukast more favorable; can be used in kids 2-5 yrs

Ca+ released from sarcoplasm

60.

Ipratropium - class

antimuscarinic (atropine - like)

61.

Ipratroprium - indication

quick relief; additive to beta agonists

62.

Omalizumab (xolair) - class

IgE antibody inhibitor

63.

Omalizumab MOA

binds IgE on mast cells/basophils; prevents release

64.

Omalizumab - indication

persistent, mod-severe allergic asthma not controlled on oral steroids

65.

Omalizumab dosage

every 2-4 weeks; half-life 26 days

66.

Omalizumab concern

very expensive

67.

Omalizumab dosage based on

IgE serum levels -but 1+ yr post treat

68.

Omalizumab SE

HA injection site rxn URI arthralgia

69.

MOA of Omalizumab (Xolair)?

Inhibits binding of IgE to the high affinity IgE receptor on surface of mast cells and basophils

70.

Which type of patient should use Omalizumab (Xolair)?

Patient with moderate-severe persistant allergic asthma not controlled by inhaled steroids

71.

When prescribing Inhibitors of IgE antibodies, what should the dosing be based on?

IgE serum levels and body weight

40.

corticosteroids dosing therapy

oral or IV "burst" therapy

41.

corticosteroids dosing strategy long term

step down: after controlled dec 25% every 2 wks (8wks min)

42.

methylxanthines include

caffeine, theophylline, theobromine

43.

methylxanthine indication

adjuvant to inhaled steroids alt to LABA to control nocturnal symptoms

methylxanthines MOA (3)

phosphodiesterase inhib, inc CAMP-> inhibits LTE broncho/vasodilate, cardiac stim, vasodilate

44.

45.

theophylline SE's 7 NITSCHA

N/V insomnia tremors seizures confusion HA arrhyth

46.

theophylline concern

narrow therapeutic window; monitor conc

47.

theophylline interaction

is a Cyp 450 substrate; many interactions

theophylline CYP450 interaction causes

inhibitors inhibit liver metabolism; increase Theo levels inducers enhance ......cause decreased Theo

theophylline avoid CY450 INHIBITORS (inhibited hide FACE Very well)

Fluvoxamine Amiodarone Cipro Erythromycin Verapamil

theophylline avoid CY450 INDUCERS (PCPR - induce halluc)

Phenytoin Phenobarbital CBZ Rifampin

theophylline disease state interactions

smoking, hyperthy - dec Theo CHF, liver disease - inc Theo

48.

49.

50.

51.

72.

T/F: Inhibitors of IgE antibodies are cost effective for the patient

False: They are about $600 per 1 150mg. vial

73.

Intermittent Asthma - Step 1 Tx

SABA as PRN

74.

Intermittent Asthma - Step 1, w/ mod/sev viral inf Tx

SABA PRN short course systemic steroids

75.

mild persistent asthma - Step 2 Tx

daily long term control inhaled steroids or (cromolyn or nedocromil) Zafirlukast or zileuton in adults (12+YOA)

76.

mod persistant asthma - Step 3 Tx

increased inhaled steroids or add LABA or add nedocromil

77.

mod persistant asthma - Step 3 not controlled Tx

increase to high dose inhaled steroids add LABA (servent or theophylline)

78.

severe persistent asthma - Step 4 Tx

Add oral systemic steroids monitor closely

79.

LABA black box warning

inc risk for asthma-related deaths; only for uncontrolled (w/ inhaled corticosteroid or 2+ maintenance meds)

80.

Acute asthma exacerbation; FEV1 or PEF < 50% Tx

O2 90-95% sat inhaled SABA or cont albuterol oral systemic steroids (prednisone) anti-cholinergics (never alone)

81.

which drugs specifically not recommended for acute asthma

methylxanthine/theophylline mucolytic sedation abx

82.

aggressive hydration in acute asthma

not reco'd adults; maybe infants/children