short acting beta agonists - buterol: _alb_uterol, _leva_buterol, _pir_buterol

- terol: salmeterol formoterol _vilan_terol (always given in combination with fluticasone or umeclidinium)

the B2 receptor is a Gs GCRP the drug binds B2 receptor which activates membrane adenylate cyclase (AC) active AC cleaves ATP into cAMP cAMP --\> + PKA PKA opens K+ channel K+ effluxes along [] gradient --\> hyperpolarization of smooth muscle ells --\> smooth muscle relaxation (bronchodilation)

both: muscle tremor nervousness, excitement tachycardia / arrythmias / prolonged QT HTN hyperglycemia hypokalemia _paradoxical bronchospasm_ In LABAS: the paradoxical bronchospasm can cause death . co-administration with ICS prevents risk of these asthma-related deaths

M3 receptors are Gq GCPRs normally, ACh binds M3 receptor membrane phospholipase C (PLC) becomes activated PLC cleaves PIP2 into --\> IP3 IP3 releases Ca++ --\> bronchial smooth muscle contraction --\> bronchoconstriction LAMA/SAMA blocks M3, blocking contraction

_most common:_ (seen way more in LAMA \> SAMA) upper RTI dry mouth (xerostemia) pharyngitis systemic (rare) dizziness / blurred vision tachy / HTN abdominal pain urinary retention

COPD/Asthma Flashcards by Kara Rieth

ANS mediation of the airway

SNS - bronchodilates (B2 agonism)

PNS - bronchoconstrictions, increases mucous secretion (M3 agonism)

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what are the SABAs?

short acting beta agonists

- buterol: albuterol, levabuterol, pirbuterol

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what are the LABAs?

- terol:
- salmeterol
- formoterol
- vilanterol (always given in combination with fluticasone or umeclidinium)

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SABAS & LABAS MOA

the B2 receptor is a Gs GCRP
- the drug binds B2 receptor
- which activates membrane adenylate cyclase (AC)
- active AC cleaves ATP into cAMP
- cAMP –> + PKA
- PKA opens K+ channel
- K+ effluxes along [] gradient –> hyperpolarization of smooth muscle ells –> smooth muscle relaxation (bronchodilation)

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PDE inhibitors - MOA

PDE breaks down cAMP
- PDE inhibitors inhibit PDE, maintaining high cAMP in cell
  - cAMP –> PKA
  - PKA –> open K+ channels
  - K+ efflux –> SMC hyperpolarization –> bronchodilation

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contrast the SABAs and LABAs in terms of

drug names
speed of onset
duration of action
available formulations
metabolism

SABA: - buterol
LABA: - terol
- note that formoterol, though classified as a LABA, has a rapid onset of action (3 min)

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formoterol is

what kind of drug?

has what onset & duration of action?

is a LABA, but acts like a SABA-LABA hybrid

long duration of action: 12-24 hours - like a LABA
rapid onset of action: < 5 min (3 min) - like a SABA

can be used as an for acute asthma relief (given with ICS) for children 12 yrs +

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SABAs & LABAs- clinical uses

LABAS always given with ICS*

SABS & LABAS:

acute asthma relief
- LABAS: fomoterol + ICS only (used 12+ children)
prevention of exercise induced bronchospasm
COPD

SABAS only: asthma exacerbation

LABAS only: asthma prevention & long term control

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SABAs & LABAs AEs

both:

muscle tremor
nervousness, excitement
tachycardia / arrythmias / prolonged QT
HTN
hyperglycemia
hypokalemia
paradoxical bronchospasm

In LABAS: the paradoxical bronchospasm can cause death. co-administration with ICS prevents risk of these asthma-related deaths

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SABA & LABA drug drug interactions

non-selective B-blockers (propanolol, carvedilol): counteraction of bronchodilatory effects
SABA & LABA with eachother: worsen AEs
successive doses: can cause tachyphylaxis - a diminshing to response to B2 agonists as a result of desensitization

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SABAs & LABAs should be used in caution with what patients?

CV issues:
- arrythmias
- HF
- HTN
diabetes (risk of exacerbating hyperglycemia)
hyperthyroidism (B2 agonism cause thyroid hyperactivity)

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SAMA & LAMAs - name of drugs

short acting/long acting M3 muscarinic receptor antagonists

- tropium

SAMA: ipratropium
LAMA: tiotropium

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SAMA/LAMA MOA

M3 receptors are Gq GCPRs
- normally, ACh binds M3 receptor
- membrane phospholipase C (PLC) becomes activated
- PLC cleaves PIP2 into –> IP3
- IP3 releases Ca++ –> bronchial smooth muscle contraction
  - –> bronchoconstriction
LAMA/SAMA blocks M3, blocking contraction

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B2 agonists vs M3 blockers - efficacy in tx of asthma & COPD

asthma: B2 >>> M3

COPD: B2 < /= M3; M3 has less AEs

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contrast SAMAs and LAMAs in terms of

onset
duration of action
formulations available
metabolism
clinical uses

both: COPD

SAMA: ipratropium

for severe acute asthma exacerbation (not for maintenance)
- like SABAs
- MUST be given w/ SABAS

LAMA: tiotropium

asthma maintanence tx in patients over >/= 6 years (not for exacebation)
- like LABAs

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SAMAS/LAMAS AEs

most common: (seen way more in LAMA > SAMA)
- upper RTI
- dry mouth (xerostemia)
- pharyngitis
systemic (rare)
- dizziness / blurred vision
- tachy / HTN
- abdominal pain
- urinary retention

what is tiotroprium?

a LAMA

what is iptratropium?

a SAMA

what is theophylline?

where is found?
how does it treat airway disease (MOA)?
PK?
clinical uses?
what should it NOT be used for?
AEs?

a methylxanthine
found in tea
MOA:
- blocks PDE-3 (& PDE-4) inhibiting cAMP breakdown
- blocks adenosine A-1 recptor inhibiting bronchoconstriction
PK:
- IV/ oral
- half life - highly variable (2-40 hrs)
  - depends on age, hepatic function, lung function
- therapeutic index - narrow
clinical use:
- as an add on for long term asthma control in pts > 12 yrs
- COPD
NOT used for
- acute asthma
- children under 12
AEs:
- cardiac arrythmyias / seizures
- like other bronchodilatory drugs (B2, M3) - muscle tremor / tachy
- abdominal discomfort / peptic ulcer

what are the i_nhaled_ corticosteroids (ICS)?

- asone:

fluticasone
beclomethasone
mometasone
budesonide: formoterol + ICS*

what are the oral corticosteroids?

prednisone

what is budesonide?

formoterol (LABA) + ICS

corticosteroids MOA

drugs cross the cell membrane then bind to nuclear receptor
- they modulate transcription to decrease expression of proteins - phospholipase A2 (PLA2), COX-2, other pro-inflammatory cytokines- that are involved in the prostaglandin synthesis pathway, reducing production of:
  - prostaglandins
  - leukotrienes
    - this takes time - thus, steroids have slow onset of action

ICS

clinical uses
onset of action
PK
AEs

clinical uses:
- persistent asthma, either
  - 1. alone
  - 1. with LABAS
- acute bronchospasm relief: in combo with formoterol (budesonide)
onset of action: 24 hrs (slow, due to MOA).
- max effects really seen 1-2 weeks post starting
PK: poor bioavailability - low systemic effects
AEs:
- RTIs: rhinitis / nasal congestion , sinus infection
- oral candidiasis*

what are ICS _not_ first choice for?

COPD

what are the leukotriene modifers and their MOAs/

two classes * **Zileuton** * lipoxygenase inhibitor * inhibits an enzyme that generates luekotrienes (in arachadonic acid pathway) * **-lukast:** montelukast, zariflukast * block leukotrienes from binding receptors

leukotriene modifers - clinical uses

* alternative therapy for _mild persistent_ asthma * severe persistent: add with ICS * prevention of exercise induced asthma (**as an alternative to SABAs**) * **AERD/NERD** (aspirin induced/NSAID induced respiratory disease) * as an add on * as prevention

explain the role of leukotriene inhibirs in the treatment of AERD/NERD

**zileuton, - lukast** AERD/NERD: aspirin/nsaid induced respiriatory disease * taking aspirin blocks COX-1/COX-2 from converting AAs into prostaglandins * AA accumulates and is redirected to leukotriene synthesis pathway * excess leukotrienes cause bronchospasm / mucus secretion /nasal congestion in URT * inhibitors work by: * inhibit *5-lipooxygenase enzyme* converting AA --\> LTs (zilueton) * blocking LTs from their receptor (-lukast)

montelukast * what type of drug * clinical uses * PK * onset * duration of action * dosing * AEs

* leukotriene inhibitor * uses: persistent asthma (monotherpy in mild, + severe) / AERD (add on) / exercise induced asthma (as prevention) * PK: metabolized by **CYP-3A4**, 2C8, 2C9 * dosing: **oral once daily** * _duration \> 24 hr_s * AEs: **serious neuropsychiatric events** (behavior/mood changes)

zafirlukast * what kind of drug * clinical uses * PK * dosing * duration of action * AEs

* leukotriene inhibitor * clinical uses: uses: persistent asthma (monotherpy in mild, + severe) / _AERD (add on)_ / exercise induced asthma (as prevention) * PK * dosing: **oral 2x daily** * ****duration of action: _12 hrs_ * AES: n/a

zilueton * what kind of drug * clinical uses * PK * duration of action * dosing * AEs

* leukotriene inhibitor (*lipooxygenase inhibitor*) * clinical uses: persistent asthma (monotherpy in mild, + severe) / AERD (add on) / exercise induced asthma (as prevention) * PK * dosing: **oral 4x daily** * AEs * headache * **hepatotoxicity (elevates ALT)**

cromolyn * what kind of drug * MOA * clinical uses

* mast cell stabilizer * MOA: inhibits _degranulation_ of mast cells & response of esionophils to inhaled antigens * clinical uses: * prevention of * exercise indueed asthma * allergen indued asthma * mild persistent asthma (as an alternative) * AEs * transient cough * mild wheez * bronchospasm after cough (rare)

what are leukotriene inhibitors _not_ to be used for?

**acute asthma exacerbation**

what can be given to relieve bronchospasm secondary to use of cromolyn?

SABAs (- buterol)

omalizumab * what kind of drug? * MOA? * clinical uses? * AEs?

* a biologic * MOA: neutralizes IgE (is an anti IgE antibody) * cinical uses: as an on add on for _maintence_ of **severe allergic asthma** with **_elevated IgE_** in patients that * =/ \> 6 yrs old * are not responding to ICS + LABA * AEs * anaphylaxis

**_res_**lizumab, **_mepo_**liaumab, **_benr_**alizumab * what kind of drug? * MOA? * clinical uses

* biologics * MOA: inhibit IL-5 * reslinzumab, mepolizumab = anti- IL-5 antibodies * benralizumab = anti-IL-5 receptor antibodies * uses: add on maintenane treatment of **severe asthma** in **adults** with an **esionophillic phenotype** * AEs * reslizumab = anaphylaxis * benralizumab = antibody development

duplimumab * what kind of drug? * MOA? * clinical uses * AE

* biologic * inhibits IL-4Aa (IL4-4Ra antagonist) * clinical uses: * as add on _maintenance_ treatment of **moderate and severe** asthma in patients with an **eiosonophillic phenotype** * in severe, **corticosteroid dependent** asthma * AE: antibody development

what are the best medications to use for prevention of exercise induced bronchoconstriction?

given as prophylaxis: * **SABAS (albuterol)** * ****given 5-30 minutes before exercise * **montelukast** * give 2 hrs before exercise * _last 24 hours_ * _useful in young children_\*\*