exam 2 pulm

What class of beta blockers are used in COPD patients?

Selective (BMEAN), lower mortality

What is primarily effected by chronic bronchitis?

goblet cells and the glands, hyperactivity will lead to overproduction of mucus and narrowing of the airways

With emphysema there is destruction of ___

alveoli

What naturally activates the M3s?

acetylcholine (bronchial constrict the airways)

In COPD, ____ are not very effective

SABAs

ACh activation of M3 receptors most likely has what effect?

bronchial constriction

COPD is characterized by what?

chronic inflammation of the small airways

What are the two classes of COPD?

1. emphysema (alveolar wall destruction)

2. chronic bronchitis (airflow and mucus production)

What immunemediators attribute to COPD?

neutrophils

macrophages

cytotoxic T-lymphocytes

T helper 17 cells

Key points of COPD

irreversible and progressive

largely corticosteroid resistant

COPD pts have many comorbidities (IHD, HTN, CHF, Diabetes, depression)

COPD definition

airflow limitation that is not fully reversible, it is progressive and associated with abnormal inflammatory response

COPD patients typically present with what symptoms?

dyspnea

chronic cough

sputum production

COPD precipitating factors

Tobacco smoke (85-90%) --> vaping is also an issue but less evidence as of right now

Occupational

Genetic

Cigarettes inhibit what?

ciliary movement

How does smoking cause COPD?

fibrosis/airway remodeling (makes it harder to breathe/dilate)

alveolar wall destruction (Emphysema)

Mucus overproduction (chronic bronchitis)

What is the main difference between asthma and COPD?

asthma is reversible, COPD is not

Blue bloaters

chronic bronchitis patients (increased mucus production)

Pink puffers

Emphysema (alveolar wall destruction)

Chronic bronchitis definition

a persistant cough with sputum production for at least 3 months in 2 consecutive years

How is chronic bronchitis characterized?

inflammation of airways

hypertrophy of large airway mucous glands

increase mucous secretion

mucus obstruction of airways

ventilation/perfusion mismatching (decreased O2 and increased PC) that can lead to respiratory acidosis and polycythemia --> cyanosis

Emphysema

destruction of septa (decreased elastic recoil) --> work to breathe in and breathe out

less mucus production

smooth muscle hypertrophy

red and pink

What two SABAs are used in COPD?

albuterol (Ventolin) and levalbuterol (Xopenex)

B2 agonists are the most potent what?

bronchodilators

What is the most effective drug in COPD patients?

LAMAs, anticholinergic drugs may be as effective as or even superior to B2 agonists by inhibiting PNS

LAMAs have what effect?

Improve lung function

Reduce exacerbations

Reduce mortality

LAMAs decrease ___ and increase ___

mucus production and dilation

Anoro Ellipta

vilanterol + umeclidinium (LABA + LAMA)

Stiolto Respimat

olodaterol + tiotropium (LABA + LAMA)

Duaklir Pressair

formoterol + aclidinium (LABA + LAMA)

Bevespi Aerosphere

formoterol + glycopyrrolate (LABA + LAMA)

Trelegy Ellipta

fluticasone furoate/umeclidinium/vilanterol (LABA/LAMA/ICS)

Breztri Aerosphere

budesonide + formoterol + glycopyrrolate (LABA + LAMA + ICS)

Atrovent

Ipratropium (SAMA)

Spiriva

Tiotropium (LAMA)

Tudorza

Aclidinium (LAMA)

Incurse Ellipta

Umeclidinium (LAMA)

Glycopyrrolate

LAMA

Revefenacin

LAMA (nebulizer)

Major complaint of antimuscarinics

dry mouth

Combivent

ipratropium/albuterol (LABA/SABA)

ICS are ____ in the treatment of COPD than asthma

far less effective, resistant to therapy

When are ICSs effective in COPD?

reducing exacerbations in severe patients, increased blood eosinophils (over 300)

ICSs are more effective as __

triple therapy (ICS + LABA + LAMA)

Corticosteroids decrease __ and indirectly decrease __

inflammation and hyper-responsiveness, airway flow

In COPD, ICSs do not what?

address the underlying cause of the disease

Which steroids are systemic?

Dexmethasone

Prednisone

Prednisolone

Methylprednisolone

QVAR

Beclomethasone (most potent)

Nasonex

Mometasone

Asmanex

Mometasone

Flonase

fluticasone

Beconase

beclomethasone

Rhinocort

budesonide

Pulmicort

budesonide

Alvesco

ciclesonide

Arnuity

fluticasone furoate

Flovent

fluticasone propionate

Airsupra

budesonide/albuterol

Dulera

mometasone/formoterol

Major steroid side effects

hoarseness and dysphonia

thrush

Theophylline

Xanthine derivative

Narrow TI

Substrate 1A2, 2E1, and 3A4

Weak PDE antagonist

Causes some bronchial dilation and anti-inflammatory response

What affect does blocking the PDE4 have?

increases levels of cAMP and decreases degranulation

Roflumilast. brand name

Daliresp

Roflumilast (Daliresp) MOA

selective PDE4 antagonist --> less degranulation and inflammation but not as potent so cannot be used as monotherapy

Dupilumab brand name

Dupixent

Dupilumab (Dupixent) MOA

monoclonal antibody directed against the IL-4a co-receptor for both IL-4 and IL-13

When is Dupilumab (Dupixent) used?

As adjunct therapy to reduce rate of exacerbation in COPD with high eosinophil levels

Azithromycin MOA

Inhibitor of bacterial protein synthesis by reversibly antagonizing the 50S ribosomal subunits which terminates protein synthesis by interfering with transpeptidation and translocation, also has anti-inflammatory properties

Bacterial infections can ___

precipitate COPD exacerbation

Azithromycin side effects

GI distress (may cause loss of potassium)

QTc prolongation (potassium channel blockade)

COPD is a ___

progressive abnormal inflammatory response to airborne chemicals

What problem is associate with COPD?

chronic inflammation with lung damage

What is the long term management of COPD?

LABAs/LAMAs/ICS combos, antibiotics, and PDE-4 inhibitors

B2 selectivity is driven by what?

aryl and bulky R groups

Lipophilicity is driven by what?

bulky R groups

Why is albuterol short acting?

direct conjugation metabolism by sulfotransferases (STs)

Which isomer of albuterol is metabolized faster?

R isomer is metabolized faster than S-isomer (so the S isomer lingers around longer than the R isomer)

S-isomer has what effects?

inflammatory

COMT =

catechol

Why are LABAs long acting?

non catechol aryl groups resist COMT

bulky N-R groups resist MAO

slower metabolism = longer duration of action

Formoterol is a ___ mixture

racemic

Arformoterol

R-R isomer and is 1000x more potent than S,S and 2 fold more potent than racemic mixture

What groups impart B2 selectivity in formoterol?

m-Formamide-OH-phenyl and Isopropyl-p-methoxy phenyl group

major formoterol metabolism

UGT, O-Glucoronidation

Salmeterol

Serevent Diskus

Athletes can abuse __

salmeterol

Vilanterol is a __

ante-drug --> when it becomes systemic it is deactivated

Olodaterol

Striverdi Respimat

Olodaterol is a ___

hydroxybenzoxazine

Olodaterol pharmacological category

Ultra long acting beta adrenergic

Why is olodaterol long acting

resistant to COMT and MAO

Accumulates in lung tissue due to lipophilicity

Olodaterol metabolism

2C8/2C9, UGTs

Catechol replacements for COPD

:)

SABA/LABA SAR summary

:)

Muscarinic antagonists are derived from what?

atropine and scopolamine (wears and epoxide hat)

What promotes local activity in anti muscarinics?

ionized quarternary amine or ionizable N

M3 antagonists block __

cholinergic bronchoconstriction

Ipratropium (Atrovent) can be classified as a ___

amino alcohol ester, SAMA

What aspect of metabolism will minimize anticholinergic effects?

esterase hydrolysis

Ipratropium + Albuterol

Combivent

Tiotropium (Spiriva) and Aclidinium (Tudorza) are both ___

LAMAs and amino alcohol esters