Drugs for Pulmonary Disorders Flashcards
What is the main advantage of drug delivery by the respiratory system?
- Rapid, efficient delivery
What is aerosol drug administration?
- Suspension of liquid and fine solid particles
What is the advantage of aerosol drug administration?
- Delivered to site of action with limited side effects
Can aerosolized drugs produce systemic effects?
Yes. If high enough dose is administered, it will reach systemic circulation
What are the 3 types of aerosolized drug administration?
- Nebulizers
- Dry Powder Inhaler
- Metered dose inhalers
Which type of aerosolized drug administration converts a liquid to a fine mist?
Nebulizer
Which type of aerosolized drug administration is a propellant?
Metered dose inhaler
Which type of aerosoloized drug administration is a powder used for inhilation?
Dry Powder Inhaler
What are 3 common problems with aerosol drug administration?
- Difficulty self-administering drug leads to incorrect dosage
- Altered breathing patterns affect administration
- Deposition of the drug into the oral mucosa
Which type of aerosol administration most negates incorrect dosing due to altered breathing patterns?
- Nebulizer
What is a downside to a nebulizer?
- Takes a long time to administer
- Cleaning after every session is time consuming
What is a common pulmonary chronic disease that affects millions worldwide?
Asthma
What are the 4 features of asthma?
- Airway inflammation
- Airway hyperresponsiveness
- Bronchoconstriction
- Hypersecretion of mucus
What is atopy?
- Inherited predisposition to allergic diseases such as asthma, allergic rhinitis, or eczema
What condition does atopy underlie in almost all children, and most adults?
- Asthma
What immunoglobin is typically elevated in patients with asthma?
- Immunoglobin E (IgE)
What white blood cells are more common in inflamed airways than in normal airways?
Eosinophils
What glands hypertrophy in inflamed airways?
Mucus
Where does edema occur in inflamed airways?
Space between smooth muscles cells and epithelium
What are the 3 goals of therapy in reducing airway inflammation?
- Terminate acute bronchial constriction
- Reduce inflammation
- Reduce hypersecretion of mucus
What is the distinguishing feature of COPD?
- Airflow limitation is not reversible
What are 2 examples of COPD?
- Chronic bronchitis
- Emphysema
What are the 4 treatment goals of COPD?
- Reduce inflammation
- Relieve bronchoconstriction
- Reduce risk of/ treat infection
- Control cough
What type of material is COPD usually related to?
Toxins such as:
- Coal
- Cigarette smoke
- Etc…
What is a persistent risk due to chronic bronchitis? why?
- Excessive secretions can lead to infection
What is the type of drug typically used to treat acute bronchoconstriction?
- Beta-2 Adrenergic Agonists
- Stimulate B-2 receptors in the smooth muscle of the brochi and bronchioles
Describe the 4 step process by which B-2 agonists relax bronchioles.
- B-2 receptor stimulation increases activity of enzyme adenylcyclase
- Adenylcyclase increases production of intracellular cyclic AMP
- Intracellular cyclic AMP activates protein kinase A
- Protein kinase A inhibits phosphorlation of myosin, and lowers intracellular ionic calcium concentrations
- Results in relaxation of smooth muscle of bronchioles
What drug stimulates both B-1 and B-2 receptors?
Epinephrine
What are the advantages of a B-2 selective agonist vs non-selective?
- Limits cardiac effects
- Limits increase in heart rate
When may epinephrine be used to treat bronchoconstriction?
- When it is in an acute phase to provide rapid therapeutic effect
What is a severe prolonged form of asthma that is unresponsive to standard drug treatment?
- Status asthmaticus
What 3 conditions may epinephrine be used to treat?
- Bronchiolitis
- RSV
- Status asthmaticus
What are the 4 classifications of Beta-2 Adrenergic Agonists in terms of duration of drug action?
- Ultra-short acting (2 - 3 hours)
- Short-acting (SABA) (3 - 6 hours)
- Intermediate Acting (8 Hours)
- Long-acting (LABA) (12 hours)
What are 2 ultra-short acting beta agonists?
- Isuprel
- Bronkosol
What are 3 short-acting beta agonists?
- Metaprel/ Aluprent
- Brethine
- Maxair
What are 3 intermediate-acting beta agonists?
- Proventil
- Xopenex
- Tornalate
What are 2 long-acting beta agonists?
- Serevent
- Foradil
What are 3 side-effects of high-dose inhalers?
- Shaking
- Nervousness
- Tachycardia
Why will a B-2 agonist cause tachycardia?
- Drugs are selective for B-2, but not exclusively
- Will bind to B-1 if B-2 are occupied
What is levalbuterol?
- 60:40 R:S isomer of B-2 agonist
- May alleviate some side effects
What is Formoterol/ Foradil?
- Highly selective Beta-2-agonist with a long duration of action
Why does Formoterol/ Foradil have such a long duration of action?
- Formoterol is highly lipophilic when entering the plasma membrane in a “drug depot”
- It is gradually released into its aqueous phase, which activates the B-2 receptors
What may occur if SABAs are overused?
- Tolerance by desensitization of B-2 receptors
How may tolerance to SABAs be reversed?
With inhaled corticosteroids
What condition may result from SABA tolerance?
Status asthmaticus
What receptors do inhaled anticholinergics act on?
Block muscarinic cholinergic receptors
What is the 3-step mechanism of action of inhaled anticholinergics?
- Decrease in the formation of cGMP
- Decreases contractility of smooth muscle in the lung
- Inhibits bronchoconstriction and mucus secretion
Are inhaled anticholinergics used for acute occurances, or for control?
Control
What condition are anticholinergics typically used for?
- COPD
What are 3 types of anti-cholinergics?
- Ipratropium bromide/ Atrovent
- Ipratropium + albuterol/ Combivent
- Tiotropium/ Spiriva
What are 6 side-effects of anti-cholinergics?
- Dry mouth
- Nervousness
- GI upset
- Headache
- Worsening of narrow-angle glaucoma
- Prostatic hypertrophy
What is the difference between Atrovent and Spiriva?
- Spiriva has a longer half-life due to slow disassociation rate from muscarinic receptors
What are the primary actions of inhaled corticosteroids in the lungs?
- Suppress inflamation in airways (limit hypertrophy of mucus cells, reduce edema, repair damaged epithelium)
- Increase number and sensitivity of B-2 receptors (increase effectiveness of B-2 agonists)
Are PO or IV administration of corticosteroids more effective for acute severe asthma attacks?
Act about the same
How long does it take for systemic corticosteroids to take effect?
48 - 72 hours.
Why should systemic corticosteroids be titrated down before discontinuing use?
- Activate glucocortizoid receptors
- These function through negative feedback
- Body detects the change in cortisol levels, and slow production at the adrenal gland
- If drug is not administered, there may be a severe drop in systemic cortisol
Are long-term systemic or inhaled corticosteroids more associated with serious adverse effects?
- Systemic
What are 6 adverse effects of systemic corticosteroids?
- Adrenal gland atrophy
- Peptic ulcers
- Hyperglycemia
- Osteopenia & Osteoporosis
- Aseptic necrosis of the hip
- Immune suppresion
What are 6 unpleasant side effects of systemic corticosteroids?
- Moon face
- Redistribution of weight
- Thin skin
- Acne
- Fatigue
- GI disturbance
What are 5 inhaled corticosteroids?
- Fluticasone (Flovent Diskus)
- Budesonide (Pulmicort)
- Triamcinolone (Azmacort)
- Flunisolide (Aerobid)
- Beclomethasone (Qvar, Beclovent)
What are 2 oral corticosteroids?
- Methyprednisolone (Depo-Medrol)
- Prednisone (Deltasone etc)
What is usually paired with an inhaled corticosteroid?
Nasal spray
Why is fluticasone proprionate/ Flovent have little bioavailability outside of the airway?
- Rapidly inactivated by the liver (CYP450 3A4 pathway)
- The metabolite that is produced has limited affinity for the glucocorticoid receptor
What are 2 examples of medications with a corticosteroid and bronchodilator component?
- Fluticasone and salmeterol (Advair Diskus)
- Budesonide and formoterol (Symbicort)
What is the advantage of combination agent aerosol medications?
Convenience
What drug are methylxanthines chemically related to?
Caffeine
What are 2 examples of methylxanthines?
- Theophylline (Theo-Dur, etc)
- Aminophylline (Somophyllin)
What 2 other pulmonary effects do methylxanthines have other than bronchodilation?
- Inhibit pulmonary edema by decreasing vascular permeability
- Increase ability of the cilia to clear mucus
What 4 non-pulmonary effects do methylxanthines have?
- Increase CO
- Peripheral vasodilation
- Mild diuretic effect
- CNS stimulation
Why are methylxanthines not often prescribed?
Narrow therapeutic index
Why must methylxanthines serum levels be monitored regularly?
- Narrow therapeutic index
- Normal caffinated drinks can raise levels easily
What the mechanism of action of mast cell stabilizers?
- Inhibit the release of histamine from mast cells
In what stiuations are mast cell stabilizers used?
- In prophylaxis to prevent acute asthma attacks
How long is the half-life of mast cell stabilizers?
2.5 hours
What are 2 mast cell stabilizers?
- Cromolyn (Intal)
- Nedocromil (Tilade)
What are Leukotriene?
- Strong chemical mediators of bronchoconstriction, inflammation, and mucous secretion
How are Leukotrienes formed?
By the lipoxygenase pathway of arachidonic acid metabolism in response to cellular injury
What type of medication treats Luekotrienes?
- Leukotriene modifiers
What is the indication for Leukotriene modifiers?
- Long-term treatment of asthma and allergies
- Acts on pathways related to long-term inflammation
What are 3 Leukotriene Modifiers?
- Zileuton (Zyflo)
- Montelukast (Singulair)
- Zafirlukast (Accolate)
What is the mechanism of action of Zyflo?
- Reduces formation of leukotrienes by blocking lipoxygenase
What is the mechanism of action of Singulair and Accolate?
- Block luekotriene receptors
What is the mechanism of action of Omalizumab (Xolair)?
- Binds to immunoglobulin E, preventing attachment to mast cells and basophils
- Prevents release of pro-inflammatory and pro-allergic substances
For whom is Xolair prescribed?
- Severe, persistent asthma that can’t be controlled even with high doses of corticosteroids
What is the meachanism of action of Mucolytics/ Expectorants?
- Reduce viscosity of bronchial mucous and aid in its removal
What is an OTC mucolytic?
- Guaifenesin (Robitussin, etc…)
What are 2 prescription examples of mucolytics/ expectorants?
- Acetylcysteine (Mucomyst)
- Dornase Alfa-Recominant (Pulmozyme)
What is the function of antitussives?
- Dampen the cough reflex
What are 2 examples of opoid antitussives?
- Codeine
- Hydrocodone bitartrate (Hycodan)
What are 2 examples of non-opoid antitussives?
- Benzonatate (Tessalon)
- Dextromethorphan (Pediacare, etc…)
What is the active ingredient in vicadin?
- Hydrocodone bitartrate
What is respiratory distress syndrome?
- Condition where lungs are not producing surfactant
In whom does respiratory distress syndrome most often occur?
- Infants
What is the function of surfactant?
- Lines inner surface of alveoli allowing the lung to remain open during respiration
What type of cell produces surfactant?
Type II/ Chief cells
What are 2 drugs used to treat RDS?
- Colfosceril (Exosurf)
- Ceractant (Survanta)
What is Respiratory Syncytial Virus?
- Virus affecting infants and young children
How is respiratory syncytial virus treated?
- RSV antibodies given during RSV season to reduce risk of infection
What is anaphylaxis?
Severe, sometimes life-threatening allergic reaction to a variety of agents
What are 3 classes of agents that may cause anaphylaxis?
- Foods
- Stinging insects
- Medications
What are some symptoms of anaphylaxis?
- Itching
- Can’t breath
- Throat swells
- Lungs constricted
- Vascular permeability shift –> edema
What is the pathophysiology of anaphylaxis?
- IgE forms during the first exposure to the allergen
- IgE attaches to mast cells and basophils
- At the 2nd exposure, the mast cells and basophils release chemical mediators
What 3 effects do the chemical mediators of anaphylaxis cause?
- Smooth muscle constriction causing bronchospasm and cramping
- Increased vascular permeability (50 % of vascular volume shifts to tissues)
- Vasodilation
Why may someone have a reaction to penicillin when they’ve never had it before?
May have been exposed to a chemically similar drug such as cephalosporin
What type of hypersensibility are most allergic reactions?
- Type 1
What drug is used to treat anaphylaxis?
- Epinephrine
What are the 2 effects of epinephrine?
Alpha-agonist: - Increased peripheral vascular resistance - Reverse vascular permeability Beta-agonist: - Bronchodilation - Positive ionotropic effect
