Chest/Respiratory Pharmacology

where does asthma airway obstruction occur

peripheral airspaces (bronchi)

3 mechanisms that produce airway resistance in asthma

bronchospasm

mucosal edema

mucus plugging

3 mechanisms that produce airway remodeling in asthma

smooth muscle hyperplasia

goblet cell metaplasia

mucus gland hypertrophy

FEV1 % that is severe asthma classification

< 60%

COPD causes what kind of obstruction?

persistent, often progressive, airflow obstruction

reversibility of COPD

non-reversible

type A COPD is _ predominant

emphysema predominant

Type B COPD

bronchitis predominant

what spirometry data is needed to establish COPD diagnosis

FEV1/FVC ratio <0.7 post bronchodilation

is COPD persistent or non-peresistent

persistent (hence chronic)

pink puffers

emphysema

corticosteroids MOA

bind glucocorticoid receptors → inhibit transcription → decrease release of inflammatory products → INDUCE transcription of anti-inflammatory products → reduce airway hyperactivity

corticosteroids long term effect for treating obstructive disorders

reduce airway hyperactivity

what places someone in E category for COPD

2+ exacerbation

1+ hospitalization

what makes corticosteroids especially beneficial for asthma

they have DIRECT anti-inflammatory effects (by producing anti-inflam products)

preferred route for corticosteroids

inhaled

first line asthma medication tx

inhaled corticosteroids

when are systemic steroids used

ACUTE exacerbations

severe persistent

when are IV CS used

acute, SEVERE exacerbations (status asthmaticus)

unable to take PO meds

indications for inhaled CS

asthma

eosinophilic esophagitis

COPD (off label)

_ should never be used as monotherapy in COPD

inhaled corticosteroids (ICS)

adverse rx’s of ICS

hoarseness

oral thrush

cough

URIs

sore throat

adverse reactions of ORAL steroids

insomnia

increased appetitie

hyperglycemia

psychosis

edema

risk of oral steroid side effects depends on._

dosage and duration

CI’s for steroids

hypersensitivity

fungal infections

monitoring for corticosteroids

BP if taking with MAOIs/TCAs

systemic infections

sympathomimetics drug classes

alpha adrenergic stimulation

B1 agonists

B2 agonists

B2 receptors physiological effects

bronchoDILATION

vasoDILATION

enhanced mucociliary clearance

B2 agonists MOA

stimulate beta receptors → active adenyl cyclase → increase intracellular cAMP → bronchodilation, less inflamm mediator release, increased mucociliary resistance

how are B2 drugs MOA different than steroids MOA

inhibiting inflammatory products production only (no direct anti-inflammatory products produced)

SABA duration

~3 hours

SABA place in therapy for asthma

second line (PREVIOUSLY first line)

used for acute asthma exacerbations

prophylaxis for exercise induced asthma

albuterol vs levalbuterol

levalbuterol is more specifiic to B2 receptors

LABA duration

12 hours

important to give _ for patients with nocturnal symptoms

LABA

don’t use _ as monotherapy in asthma

LABA

combo LABA drugs (both asthma/COPD)

salmetrerol

formoterol

vilanterol

COPD only LABA’s

afromoterol

indacaterol

olodaterol

vilanterol/umeclidinum

SE’s of B2 agonists

heart symptoms (palpitations, HTN, HA, tachy)

paradoxical bronchoconstriction

HYPOkalemia

HYPERglycemia

B2 agonist monitoring

hypokalemia (duiretics)

blood sugar

BP if taking MAOIs or TCAs

epinephrine is what kind of molecule

catecholamine

MOA of epinephrine

quick bronchodilation + increased gas exchange

smaller doses of epinephrine have higher affinitiy for _

beta receptors

larger doses of epinephrine have higher affinity for _

alpha receptors

route of admin for epinephrine

IV

inhaled/nebulizer

epinephrine indications

bronchospasm

croup

acute asthma attack unrelieved by albuterol

anaphylaxis

SE’s of epinephrine

cerebral hemorrhage

cardiac arrythmias

pulm edema

worsening cardiac sx’s in hyperthyroidism and cocaine use

when is a lower dose of epinephrine recommeneded

hyperthyroidism or cocaine use

muscarinic antagonist MOA

block acetylcholine from binding → bronchodilation, reduced vagal tone in airways, reduced mucus gland secretion

short acting muscarinic antagonist

irpatropium bromide

long acting muscarinic antagonists

tiotropium

revenfenacin

aclidinum

glycopyrrolate

umeclidinium

ipratropium indications

combo use with SABA for acute asthma exacerbation

first line for COPD exacerbation

bronchospasm

side effects of ipratropium

chest pain, palpitation

CNS effects (anti-cholinergic)

caution groups for ipratropium

glaucoma

BPH

geriatric population

which LAMA is contrainidcated in severe renal impairment

tiotropium

which LAMA is not recommended in hepatic impairment

reverfenacin

which LAMA is used in combo with LABA and ICS

umeclidinum

long acting muscarininc antagonists indications

COPD maintenance treatment

LAMA use with caution groups

glaucoma

Myasthenia gravis

BPH

bladder neck obstruciton

renal impairement

avoid contact with _ for LAMAs

eyes (blurred vision)

adverse effect of LAMAs

paradoxical bronchospasm

what cells synthesize leukotrienes

eosinophils

basophils

mast cells

neutrophils

normal physiological effect of leukotrienes

constriction of smooth muscle

mucus secretion

leukotriene inhibitors MOA

bind to cysteinyl leukotriene receptors → inhibit actions of LTD4

where are CysLT1 receptors found

airway smooth muscle cells

macrophages

eosinophils (pro-inflam cells)

what types of effects do leukotriene inhibitors have

anti-inflammatory

bronchodilator

leukotriene inhibitor drugs

montelukast

zafirlukast

leukotriene inhibitors place in therapy

SECOND line to ICS

leukotriene inhibitors have no role in _

acute asthma exacerbations

indications of leukotriene inhibitors

chronic asthma treatment

seasonal/perennial allergic rhinitis

prevenetion of exercise induced asthma

timing of leukotriene inhibitors for exercise induced asthma

2 hours before

adverse effects of leukotriene inhibitors

HA

dyspepsia

increased LFTs

URIs

Churg-strauss syndrome (eosinophilic granulomatosis)

neuro symptoms

montelukast black box warning

neuropsychiatric effects (discontinue if occur)

NO evidence of higher suicide incidence

zafirlukast monitoring

LFTs

monitoring with montelukast

caution with CYP inducers (rifampin)

anti-IgE antibody drug

omalizumab

omalizumab MOA

inhibits IgE binding to mast cells/basophils → decreased release of allergic mediators

LESS receptors on basophils

indications of omalizumab

severe asthma (allergic)

inadequate control with ICS

AE’s of omalizumab

injeciton site rxn

HA

URI

SEVERE: anaphylaxis, churg strauss, thrombocytopenia, cancer

IgE antibody monitoring

check IgE before starting

watch for systemic infections

don’t abruptly stop corticosteroids (gradual taper better)

duplimumab drug class

anti-interleukin 4 antibodies

dupilumab MOA

bind to IL-4 subunit → inhibits IL4/IL13 signaling

decreases pro-inflammatory cytokines, NO, IgE

dupilumab indications

add on for asthma maintenance

refractory COPD

add on for eosinophilic COPD

atopic dermatitis

rhinosinusitis with nasal polyposis

dupilumab adverse rxn’s

injeciton site rxn

occular effects

dupilumab severe rxn’s

anaphylaxis

eosinophillic disorder

ensure patients are _ before starting dupulimab

up to date on all immunizaitons

anti-interleukin-5 antibody drugs (3)

benralizumab

mepolizumab

reslizumab

binding to IL-5 subunit receptor inhibits _

eosinophil recruitment and survival

what does mepolizumab bind to

IL-5 receptor on CYTOKINE

what does reslizumab bind to

IL-5 CYTOKINE

what does benralizumab bind to

IL-5 receptor on eosinophils

benralizumab MOA

binds to IL5 on eosinophils → triggers antibody-dependent cell mediated cytotoxicity → rapid eosinophil depletion

Anti-Interleukin-5 indications

severe asthma maintenance

NOT for bronchospasm

Anti-Interleukin-5 should not be used for _

acute bronchospasm

Anti-Interleukin-5 minitoring

PFTs (FEV1)

hypersensitivity rxn’s

reslizumab black box warning

anaphylaxis

Anti-thymic Stromal Lymphopoietin Inhibitor drug

tezepelumab

tezepelumab MOA

binds thymic stromal lymphopoietin (epithelial cytokine) → reduced cytokines and eosinophils

tezepelumab indications

add on therapy for severe asthma

history of asthma exacerbations

don’t use tezepelumab for _

acute exacerbations