NSC 830 Drugs that Affect the Respiratory Systemcourses.hs.eku.edu/nsc830/week4/pdf/respiratorymeds.pdf8/13/2015 1 Drugs that Affect the Respiratory System BROOKE BENTLEY, PHD, APRN

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Drugs that Affect the

Respiratory SystemBROOKE BENTLEY, PHD, APRN

Goals of Therapy

Asthma� Prevent symptoms

� Decrease use of SABAs

� Maintain normal pulm function & prevent loss of lung function

� Maintain QOL including attendance at school, work and physical activities

� Prevent exacerbations & minimize ED visits and/or hospitalizations

� Provide optimal pharmacotherapy with minimal or no AEs

COPD� Reduce COPD symptoms

� Reduce the frequency & severity of

exacerbations and reduce hospitalizations

� Improve health status

� Improve exercise tolerance

� Minimize the impact of the medications on

other potential co-morbid conditions

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Goals of Drug Therapy

�1. dilate the airways

�2. reduce inflammation

�3. stabilize mast cells

Delivery Methods

� Correct use of Metered Dose Inhaler (MDI) inhaler:

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Delivery Methods

� Dry-Powder Inhaler (DPI)

� Dry, micronized powder delivered directly

to the lung

� Breathe in quickly & deeply

� Dose lost if patient exhales through the

device

� Avoid moister in the device

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Delivery Methods

� DPI: Spiriva: Single-dose capsules must be inserted into the inhaler prior to use

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Delivery Route

� Nebulizer

� Converts a drug solution to a mist

� Mist is inhaled through a face mask or mouthpiece

� Face mask must have snug fit

� Good for children or patients unable to coordinate use of MDIs or DPIs

� Good for home setting

� Less portable when leaving home

Adrenergics (Sympathomimetics)

� MOA: Stimulates beta 2 receptors causing the formation of cAMP (cyclic

adenosine monophosphate) in the airway tissue which results in bronchodilation

� AE: (incidence & severity will depend on the receptor selectivity (beta 2 in

bronchial smooth muscle = bronchodilation; beta 1 in heart = increased HR &

contractility) of the drug as well as the mode of administration (oral vs. inhaled)

� Cardiac:

�Tachycardia/arrhythmias/palpitations

�Worsening of angina symptoms

� CNS:

�Nervousness/anxiety/insomnia

�Tremor

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Adrenergics (Sympathomimetics)

� Special Considerations:

� Use beta 2 selective agents whenever possible to minimize side

effects

� Use inhaled drug if possible to avoid systemic effects

� Avoid excessive use to avoid tolerance and possible increases in

mortality rate

� Use with caution in patients with angina, hypertension, diabetes

mellitus, or hyperthyroidism

Adrenergics (Sympathomimetics)

� Short-Acting Beta Agonist (SABA)

� “Rescue” inhalers

� SABA agents should always be available for episodes of shortness of

breath

� Not generally meant for regularly scheduled use:

�May increase AEs

�Decrease effectiveness

�Increase airway hyper-responsiveness

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Adrenergics (Sympathomimetics)

� Short-Acting Beta Agonist (SABA)

� Asthma: if using more than 2 days/wk for symptom relief (excluding exercise-induced bronchospasm), then poor asthma control and change in therapy is needed

� Using more than 2 canisters/month is dangerous (risk for death in asthma pts)

� Exercise-induced asthma:

� School age child: Rx - dispense 2?; school form (triggers, self-administer, nurse-administer, S/S distress)

� COPD: SABA agents may help decrease symptoms, but long acting therapy is more beneficial

Adrenergics (Sympathomimetics)

� Common Drugs:

� Short-Acting Beta Agonist (SABA)

�albuterol

� Brand names:

� Proventil HFA, Ventolin HFA, ProAir HFA

�onset 5 min & duration 4 hrs

�PRN use for acute attacks

�Available forms: MDI, nebulizer

�Writing for refills?

***HFA = hydrofluroalkane (propellant)

(chloroflurocarbon (CFC) propellant removed from market by FDA in 2008)

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Adrenergics (Sympathomimetics)

� Common Drugs:

� Short-Acting Beta Agonist (SABA)

� levoalbuterol (Xopenex)

� Less cardiac side effects

� Longer duration = 8 hrs

� More expensive

� Available forms:

� Nebulizer

� Metered Dose Inhaler (MDI)

Adrenergics (Sympathomimetics)

� Long-Acting Beta Agonist (LABA)

� “Maintenance” inhalers (maintain symptom relief)

�Help decrease exacerbations and related hospitalizations

�NEVER used as monotherapy with asthma patients

�If patient on inhaled LABA & corticosteroid, then use combo

product to increase adherence

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Adrenergics (Sympathomimetics)

� Common Drugs:

� Long-Acting Beta Agonist (LABA)

� salmeterol (Serevent Diskus)

� formoterol (Foradil Aerolizer)

� Inhaled: onset 20 min & duration 12 hrs

� Maintenance inhaler

�NOT for acute attacks

� BLACK BOX WARNING:

� LABA increase risk of asthma-related deaths

Anticholinergics

� MOA: Inhibits the effect of acetylcholine in bronchial smooth muscle when given by inhalation which results in bronchodilation

� NOT indicated for “rescue” treatment

� “Maintenance” therapy = SCHEDULED medication

� Primary use = COPD

� AEs: (systemic effects rare)

� Dry mouth/bad taste in mouth

� Blurred vision/exacerbation of narrow-angle glaucoma

� Urinary hesitancy/retention

� Cough

� Dizziness

� Sinusitis

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Anticholinergics

� Common Drugs:

� ipratropium (Atrovent)

�Maintenance medication

�NOT for “rescue”

�Onset = 5-15 min Duration = 4-6 hrs

�Available forms: inhaler & nebulizer

� Combo:

�albuterol/ipratropium (Combivent Respimat) – inhaler

�DuoNeb – nebulizer

�NOT for PRN use

Anticholinergics

� Common Drugs:

� tiotropium (Spiriva HandiHaler)

� Maintenance medication

�Onset = 30 min Peak = 1.5-3 hrs Duration = 24 hrs

� Available forms: dry-powder inhaler

� QD dosing

� aclindinium (Tudorza Pressair)

� Maintenance medication

� Slightly faster onset of action

� Available forms: dry-powder inhaler

� BID dosing

�Advantage: may have less dry mouth & urinary retention; more efficacy at night

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Mast Cell Stabilizers

� MOA: stabilize mast cells & prevent the release of bronchoconstrictive & inflammatory substances when mast cells are confronted with allergens & other stimuli

� Primary use: Prophylaxis tx for asthma (may take 3 wks to see full clinical effect)

� AEs:

� Hoarseness, coughing

� Unpleasant taste

� Common drugs:

� cromolyn inhaled nebulizer

� Use for asthma: QID

� Use for exercise induced asthma: give 10-60 min prior to exercise

Leukotriene Inhibitor

� Leukotrienes = strong chemical mediators of bronchoconstriction & inflammation;

increase mucous secretion & mucosal edema

� MOA: selectively binds to leukotriene receptors

� Primary use: asthma

� AEs:

� Nausea

� Headache

� CNS: may cause aggressive behavior, hallucinations, depression, suicidality

� Common drugs:

� montelukast (Singulair) – peds: may use at 6 mo of age (granule pkt)

� zileutin (Zyflo) – common drug interactions

� zafirlukast (Accolate) – common drug interactions

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Corticosteroids� MOA: anti-inflammatory effect; decreases airway edema &

hyperreactivity

� Primary use: Asthma & COPD

� Available forms: MDI, DPI, nebulizer, PO (tablet & liquid), IM, IV

� Must be scheduled administration; NOT for PRN use

� Inhaled route often preferred (safe, effective, less systemic effects)

� Inhaled route: rinse mouth after use with water to minimize oral candidiasis

Corticosteroids

� Available forms: MDI, DPI, nebulizer, PO, IM, parenteral

� PO:

� short-term use:

�burst therapy = same dose every day for a few days (ie, Prednisone 60 mg QD X 5 days)

�dose pack = start high dose & taper every day to lower doses

�Medrol dose pack (methylprednisolone)(24 mg day 1 then taper by 4 mg qd over 6 days)

�Dex pack (dexamethasone) (6 day, 10 day or 13 day taper)

� longer, individualized wean/taper (Prednisone 2-4 wks)

�WHY TAPER?

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HPA Axis(hypothalamus, anterior pituitary, adrenal gland)

� Based on Diurnal Rhythm:

� Evening: Hypothalamus detects low levels of corticosteroids; releases corticotropin releasing hormone (CRH)

� Increased CRH triggers anterior pituitary to release adrenocorticotropin hormone (ACTH)

� Increased ACTH stimulates adrenal gland to synthesize & release corticosteroids (peak release in early morning)

� This is a negative feedback system

� If take exogenous hormones (ie, prednisone) then suppress the release of CRH & ACTH and thus, the adrenal gland is no longer stimulated to produce & secrete hormones and the gland begins to atrophy

� Must slowly taper exogenous hormones (ie, prednisone), so HPA axis “kicks back in”

� Stopping oral corticosteroids abruptly can lead to adrenal insufficiency or adrenal crisis and death

Corticosteroids

� Available forms: MDI, DPI, nebulizer, PO, IM, parenteral

� PO:

�Pediatrics?

� prednisolone (Orapred, Prelone) – oral liquid

� long-term use: alternate day dosing to reduce adrenal suppression & AEs

� Parenteral route for emergency situations:

� Considering admission to hospital: oxygenation low, tachypneic, tri-pod position,

accessory muscles

� Hospital IV steroids or IM Solumedrol

� Nebs, pulse ox, oxygen in office for a few hours

� Emergent hump?

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Corticosteroids

Inhaled

� Candidiasis

� Hoarseness

� Cough

� Headache

� Long-term use: increased pneumonia in COPD patients

Oral

� Adrenal suppression

� Immunosuppressant effect

� Osteoporosis

� Hyperglycemia

� Muscle wasting

� Hypertension

� Possible PUD

� Integument – thinned skin

� Hypokalemia & hypernatremia

Inhaled Corticosteroids

� Common drugs:

� budesonide (Pulmicort) – flexhaler DPI, respulesfor nebulizer

�Flexhaler – minimum age of 6 yo

�Respules – minimum age of 1 yo

� fluticasone (Flovent) – MDI, DPI

� Minimum age of 4 yo

� beclomethasone (Qvar) – MDI

� Minimum age of 5 yo

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Combination Products

� LABA and Corticosteroid products:

� salmeterol/fluticasone (Advair)

� Minimum age 4 yo

� formoterol/budesonide (Symbicort)

� Age >12 yo

� formoterol/mometasone (Dulera)

� Age >12 yo

�NEVER for acute attack

�Remember adverse effects from both components

Phosphodiesterase 4 (PDE4) Inhibitor

� MOA: selectively inhibits phosphodiesterase type 4 (PDE4), leading to increased intracellular cAMP (cyclic adenosine monophosphate) levels; thus reducing inflammation

� PDE4 inhibitors are NOT direct bronchodilators

� Primary use:

� Not a first line therapy; usually with COPD not well controlled on LABAs & anticholinergics

� AEs:

� GI: nausea, diarrhea, weight loss

� CNS: insomnia, anxiety, depression

� Metabolized by CYP 3A4 substrate (careful with CYP 3A4 inhibitors – e-mycin, cimetidine, fluconazole)

� Common drug: roflumilast (Daliresp)

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Methylxanthines

� MOA: exact MOA unknown; increases cAMP and leads to bronchodilation; mild anti-inflammatory & diuretic effects

� NOT a first line therapy

� AEs:

� CNS: nervousness, insomnia, tremors

� Cardiac: tachycardia

� GI: N/V, anorexia

� Narrow therapeutic index: 5-20 mcg/ml; frequent serum levels needed

� Numerous drug-drug interactions (CYP 1A2 substrate)

� Higher doses needed with cigarette smokers (b/c tobacco is CYP 1A2 inducer)

� Common drug: theophylline (Theo-24)

Monoclonal Antibody

� MOA: inhibits IgE binding to mast cells & basophils; thus, decreasing the release of mediators of the allergic response

� Primary use: uncontrolled, severe, persistent asthma in pts over 12 yo (allergic component)

� Maxed out on high dose ICS & LABA

� Available form: SQ every 2-4 wks; (very expensive)

� AEs:

� Injection site rxns

� Headache

� Viral URI

� Common drug: omalizumab (Xolair)

� BLACK BOX WARNING: anaphylaxis can occur up to 24 hrs after any dose

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Home Oxygen

� Guidelines for insurance/Medicare/Medicaid to pay for home oxygen

� DME (Durable Medical Equipment)

� Home concentrator (pull oxygen out of the air & concentrating it)

� Portable method depending on mobility

� May need conserving device: makes the tank last longer; breath actuated or gives pulses of oxygen

� Continuous flow or just HS

� Liters per minute/nasal cannula

� Humidification

� No smoking