Drugs Used to Treat Lower Respiratory Tract Disorders PART 1

what are some lower respiratory tract disorders?

- asthma

- COPD

- bronchitis

- pneumonia

what is the pathophys of asthma?

chronic inflammatory condition of the airways, can lead to remodeling of lungs

what are some triggers of asthma?

- respiratory infections

- allergens

- environment

- emotions

- exercise

- chemicals

what is the clinical presentation of asthma?

Wheezing, SOB, chest tightness, laboratory signs

what are some laboratory signs of asthma?

PFTs, FEV1, IgE, FEV1/FVC, Eosinophils

what are recommended vaccinations for those with asthma?

pneumococcal and influenza

what 3 steps does GINA suggest for asthma management?

assess, adjust, review

how can asthma control be assessed?

- symptoms

- inhaler use

- activity limitations over last 4 weeks

how can risk factors for exacerbations be assessed for asthma?

- Recent exacerbations

- inadequate ICS use

- other co-morbidities

how can asthma severity be assessed?

Level of treatment (STEP 1, 2, 3, 4, 5, or 6) needed to control sx and exacerbations

what are the goals in treatment adjustment of asthma?

- Minimize chronic sx

- prevent recurrent exacerbations

- reduce ER visits

- maintain normal pulm

function

when should periodic lung function testing be done for asthma?

- Serial spirometry at dx

- 3-6 months after treatment started

what are the components of asthma control?

- Daytime asthma symptoms > 2 x a week

- Nighttime awakening due to asthma

- Interference with normal activity due to asthma

- Reliever medication needed for asthma

symptoms > 2 X a week

what does the level of control mean for asthma?

how many of the components of asthma control have you had in last 4 weeks?

how many components would mean well controlled?

0 components

how many components would mean partly controlled?

1-2 components

how many components would mean not controlled controlled?

3-4 components

what is the goal of aerosol therapy for asthma?

Delivers drug to inflamed or constricted airways

how do you choose the device for aerosol therapy for asthma?

based on the where you want the particles to go

what are some types of devices for aerosol therapy for asthma?

- MDI

- Spacers

- DPI

- Nebulizers

what is an MDI?

meter dose inhaler, pressurized canister with metering valve

what is the propellant in MDIs?

HFA

what are spacers useful for?

pediatrics, promote airway penetration by decreasing the particle speed

what is a DPI?

dry powder inhaler

what are some cons of DPI?

- require more time and work

- can be irritating

- less popular

- no propellant so need to be able to take a deep breath

what are nebulizers useful for?

good for acute exacerbations or someone with less effective technique

how do nebulizers work?

liquid is placed in a machine and aerosolized, require minimal effort

what are some important tips for inhaler use?

- shake well before use

- exhale before use

- inhale slowly and hold it, and then slowly exhale

what receptor type are is the airway tissues?

- β2

- α

what is the response in the airways to β2 Sympathomimetic Agonists?

- Smooth muscle relaxation (bronchodilation)

- increased ciliary beat

- increased serous secretion

- inhibition of mast cell degranulation

what is the response in the airways to α Sympathomimetic Agonists?

Smooth muscle contraction (bronchoconstriction?)

what receptor types are in the heart?

- β1

- β2

what is the response in the heart to β1 Sympathomimetic Agonists?

Inotropic and chronotropic

what is the response in the heart to β2 Sympathomimetic Agonists?

Chronotropic

what receptor types are in the vasculature?

- β2

- α

what is the response in the vasculature to β2 Sympathomimetic Agonists?

- Vasodilation

- decreased microvascular leakage

what is the response in the vasculature to α Sympathomimetic Agonists?

Vasoconstriction

what receptor types are in the skeletal muscle?

β2

what is the response in the skeletal muscle to β2 Sympathomimetic Agonists?

Increased neuromuscular transmission (tremor and

increased strength of contraction)

what receptor types are in the uterus?

β2

what is the response in the uterus to β2 Sympathomimetic Agonists?

Relaxation (tocolysis)

what receptor types are in the metabolic tissue?

- α1, β1

- β2

what is the response in the metabolic tissue to α1, β1 Sympathomimetic Agonists?

- Glyconeolysis

- lipolysis

what is the response in the metabolic tissue to β2 Sympathomimetic Agonists?

Chronotropic

what is bronchodilation promoted by?

cAMP

what does the stimulation of β2 receptors result in?

bronchodilation, tachycardia, skeletal muscle tremor

what do beta agonists stimulate?

adenylyl cyclase, enhances cAMP formation and bronchodilation

what do Theophylline stimulate?

theophylline increases intracellular cAMP levels by inhibiting the enzyme phosphodiesterase (PDE), which normally breaks down cAMP, it allows for bronchodilation

what do muscarinic antagonists do?

inhibit bronchoconstriction -> bronchodilation

what stimulates bronchoconstriction?

- acetylcholine

- adenosine

what are some examples of bronchodilators?

- Methylaxthines

- Anticholinergics

- Sympathomimetics (beta-adrenergic agonists)

what is an example of Methylaxthines?

- Theophylline (TheoDur) (oral)

- Aminophyilline (injectable)

what is Theophylline rarely used?

decreased efficacy and side effects

what is the MOA of Methylaxthines?

- Inhibit PDE results in sustained elevated levels of cAMP and cGMP

- Mild anti-inflammatory action

- Increase the force of contraction of diaphragmatic muscles

what is PK metabolism of Methylaxthines?

aminophylline → theophylline → caffeine (why cardiac stimulation)

what is the excretion of Methylaxthines?

renal

describe therapeutic index of Methylaxthines

NARROW therapeutic index

who is the clearance of Methylaxthines highest?

adolescents and smokers

who is the clearance of Methylaxthines slowest?

those with heart disease, liver disease, severe respiratory disease

what are some adverse effects of Methylaxthines?

- GI

- Headache

- Anorexia, tachycardia, jitteriness

- tachyarrhythmias, respiratory arrest, seizures

what are some contraindications of Methylaxthines?

- Hepatic/renal disease

- Seizures

- Cardiovascular/ cerebrovascular disease

- Thyroid disorders

why is Hepatic/renal disease a contraindication of Methylaxthines?

affects the biotransformation and increases toxic levels

why are seizures a contraindication of Methylaxthines?

decreases seizure threshold

why are thyroid disorders a contraindication of Methylaxthines?

related to potential to HTN with thyroid issues

what are some special notes regarding Methylaxthines?

- Smoked or grilled foods can alter metabolism

- AVOID tea, coffee, chocolate, caffeinated pop

- Beta-blockers may reduce efficacy

- Dosing - theophylline ≠ aminophylline

- Aminophylline used to reverse effects of adenosine

- DDI with St. John's Wort

what are examples of anticholinergics?

- Ipratropium (Atrovent)

- Tiotropium (Spiriva)

- Aclidinium (Tudorza)

- Umeclidinium (Ellipta)

What is the MOA of anticholinergics?

Competitively inhibits acetylcholine at various muscarinic receptors

at smooth muscle in airways leading to bronchodilation

which anticholinergic requires more frequent use 3-4x daily and has a max result in 5-10 minutes?

Ipratropium (Atrovent)

which anticholinergics are dosed twice daily and have max result in 30 min - 2 hrs?

- Tiotropium (Spiriva)

- Aclidinium (Tudorza)

- Umeclidinium (Ellipta)

which anticholinergics block muscarinic receptors 1-3 ?

- Tiotropium (Spiriva)

- Aclidinium (Tudorza)

which anticholinergics block muscarinic receptors 1-5 ?

Umeclidinium (Ellipta)

what are some adverse effects of anticholinergics?

Dry mouth & anticholinergic (anti SLUDGE)

what are some contraindications of anticholinergics?

- Glaucoma

- Urinary retention/BPH

which anticholinergics is contraindicated with soy/peanut allergy?

Ipratropium (Atrovent)

which anticholinergics is contraindicated with milk allergy?

Umeclidinium (Ellipta)

what do beta-agonist binding to B1 receptors affect?

cardiac tissue

what do beta-agonist binding to B2 receptors affect?

bronchial and uterine tissue

what does a B2 adrenergic agonist cause?

bronchodilation, tremor,

tachycardia, hypotension

Patients with _________ are VERY SENSITIVE TO NON-CARDIO SELECTIVE beta blockers

asthma

what are the indications of short acting beta agonists?

management of acute episodes

what are the indications of long acting beta agonists?

prophylaxis

what is the MOA of beta-agonists?

Stimulate intracellular enzyme that catalyzes ATP to cAMP . Increased

cAMP causes relaxation of smooth muscle (bronchial)

what is monitored with beta-agonists?

- BP, HR

- IOP

- Blood glucose

what is the black box warning of beta-agonists?

avoid in acute asthma attack due to increased risk

of asthma related death (LABA)

what are some adverse effects of beta-agonists?

- Metabolic acidosis (increased lactic acid concentration)

- Tremors (due to cardiac stimulation)

what is the recommendation for those using MDI formulations?

wait 3 to 5 minutes between inhalations and shake the inhaler before use

what can epinephrine be used for?

Older agent used for asthma

what receptors can epinephrine affect?

β1 and β2 and α properties

what effect does epinephrine have?

increased vasocontriction, tachycardia

what is the inhaled epinephrine called?

racepinephrine or racemic epinephrine

what are examples of Long-acting beta-agonists (LABA's)?

- Salmeterol (Serevent Diskus)

- Formoterol (Foradil)

- Indacaterol (Arcapta)

- Olodaterol (Striverdi)

what is the MOA of LABAs?

Cause relaxation of bronchial, vascular smooth muscle (increases cAMP levels)

what are indications for LABAs?

- Prevention of bronchospasm in COPD

- Emphysema

- asthma

what are contraindications of LABAs?

- preexisting arrhythmias, angina, palpitations, chest pain

- narrow angle glaucoma

- hypersensitivity

what are some adverse reactions of LABAs?

- palpitations, tachycardia

- heartburn, diarrhea, nausea

- hyperglycemia, hypokalemia

- cough, dry throat

- Headache, anxiety

what are some conscientious considerations of LABAs?

- excessive use = tolerance

- NOT appropriate for

monotherapy

- Dosing is critical in children

- Use with beta-blockers (can reduce duration of LABA)

what is the onset of action time for formoterol?

5 mins

what is the onset of action time for salmeterol?

2-45 mins

what is the onset of action time for indacaterol?

15 mins

what is the onset of action time for olodaterol?

20 mins