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Pharm S2015 > Lecture 25: Respiratory > Flashcards

Lecture 25: Respiratory Flashcards

1
Q

Endogenous products that play important role in pathophysiology of lung:

A
  • Prostaglandins, Acetylcholine, β2–adrenergics , Histamine and Adenosine
  • ACE –angiotensin converting enzyme –Converts AT1 (Angiotensin I) to ATII
  • ACE inactivates bradykinin, which is enhanced by ACEI (e.g. captopril) that cause cough and angioedema.
  • Macrophages clears waste products
  • Ciliated columnar cell brush away mucus secretions
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2
Q

Asthma: clinical manifestations

A
  • Shortness of breath (SOB), Cough, Wheezing, Prolonged expiratory duration (↓I/E ratio), Use of accessory muscles of respiration & Chest tightness.
  • ↓O2 ,–late sign, ↑RR, ↑HR, ↑Resonance
  • Dx: Spirometry: ↓FEV1 / FVC; ↑RV & TLC (total lung capacity)
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3
Q

Asthma Rx

A
  • Antigen & IgE on mast cells: Omalizumab
    • Patients who remain symptomatic in spite of compliance with inhaled corticosteroid treatment addition of long acting β2 agonists are recommended; and for uncontrolled allergic asthma, Omalizumab is added.
  • Early response: Beta agonists, theophylline, muscarinic antagonists
  • Late inflammation: steroids, anti-leukotriene, cromolyn

Contra-indications

  • Beta blockers
  • chol drugs (carbechol)
  • adenosine
  • Prostaglandin-derivates
  • Aspirin
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4
Q

β2-adrenergic agonists that are commonly used for asthma:

A
  • Albuterol, Pirbuterol and Terbutaline are called SABAs (Short Acting β2 Agonists) – they are used for acute symptoms.
    • also used for premature labour (uterine contractions)
  • Salmeterol & Formoterol – they are called LABAs (Long Acting β2 Agonists) –not used for acute symptoms
  • Epinephrine, Isoproterenol are Nonspecific β –agonists:
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5
Q

Clinically important actions of isoproterenol

A
  • non-selective Beta-agonists
  • Beta2: bronchodilation
  • Beta2: peripheral vasodilation
  • Beta1: incr CO
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6
Q

Drugs acting on arachidonic acid products in asthma

A
  • corticosteroids
  • Zileuton
  • NSAIDS
  • Zafirlukast, Montelukast
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7
Q

Inhaled steroids used in the management of chronic asthma:

A
  • Beclomethasone
  • Flunisolide
  • Triamcinolone
  • Fluticasone
  • Budesonide

PK

  • only 10% deposited in lung
  • systemic doses at higher does; prevent by using a spacer
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8
Q

Safety to use anti-asthma drugs in pregnant women:

A
  • Pregnantwomenwithasthmacanbetreatedas aggressively as non pregnant asthmatic patients.
  • Risks of poorly controlled asthma include: pre- eclampsia, perinatal mortality, preterm labor and low birth weight.
  • Use of ICS during the 1st trimester: Congenital malformation may occur with ICS >1000 mcg/day
  • AnotherstudywithICSuseduringpregnancy: Risks of endocrine and metabolic abnormalities
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9
Q

Anticholinergics as bronchodilators:

A
  • Ipratropium (Atrovent): A short acting inhaled anticholinergic can be used in asthma, QID.
    • Prevent vagal-mediated bronchoconstriction and drug induced bronchospasm such as β blockers.
    • Adverse: dry mouth
  • Tiotropium is a long-acting anticholinergic, used once daily dosing, in COPD.
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10
Q

Zileuton (Zyflo)

A
  • inhibits 5-lipoxygenase, which catalyzes the formation of leukotrienes from arachidonic acid.
  • used for prophylaxis (does not bronchodilate)
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11
Q

Zafirlukast (Accolate)

A

LTD 4 receptor antagonist

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12
Q

Montelukast (Singulair)

A
  • LTD4 receptor antagonist
  • used for prophylaxis (does not bronchodilate)
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13
Q

Leukotriene uses

A
  • Route of administration leukotriene inhibitors: PO
  • Clinical role of Leukotriene inhibitors in asthma:
  • Useful in prevention of exercise, antigen, and aspirin induced asthma.
  • They prevent bronchoconstriction and airway inflammation. Leukotriene inhibitors are used for chronic maintenance therapy of mild asthma; they are not beneficial in acute bronchospasm
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14
Q

Zafirlukast & Montelukast

A
  • Rarely patients develop as vasculitis and systemic eosinophilia resembling Churg-Strauss syndrome.
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15
Q

Anti-IgE antibody –Omalizumab:

A
  • It is administered parenterally and an expensive drug.
  • MOA: It binds to the IgE on sensitized mast cells and prevents activation by triggers – prevents release of LTs and other mediators.
  • Used for prophylactic management in asthmatic patients and in cases of inadequate control with inhaled ICS in patients aged above 12 years.
  • Like other protein and antibody drugs, omalizumab causes anaphylaxis (a life-threatening systemic allergic reaction) in 1 to 2 patients per 1,000.
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16
Q

Theophylline MOA

A
  • Methylxanthine derivative that inhibits phosphodiesterase, the enzyme responsible for the metabolism of cAMP to AMP. Increased levels of cAMP result in bronchodilation. Theophylline has no significant anti-inflammatory effects.
  • Blocks adenosine receptors.
  • Theophylline role in asthma:
  • Limited, because it has a very small therapeutic window

Drug interactions with theophylline:

  • Cimetidine, erythromycin and quinolones(cipro) increase theophylline plasma levels.
  • Drugs that decrease plasma levels of theophylline:
  • Phenytoin, phenobarbitone and carbamazepine

Complications with theophylline overdose:

  • The most common are tremor, insomnia, GI distress, and nausea. Hypokalemia and hyperglycemia may occur.
  • most dangerous are seizures and arrhythmias.
17
Q

CROMOLYN SODIUM AND NEDOCROMIL

A
  • Mechanism of action of cromolyn sodium (Intal) and nedocromil (Tilade):
  • They are effective prophylactic agents that stabilize the membranes of mast cells and prevent the release of inflammatory mediators.
  • They are not used for treating acute attacks of asthma:
  • They are used as prophylactic agents. Pretreatment with cromolyn or nedocromil blocks allergen- and exercise-induced bronchoconstriction.
  • Other uses: for preventing food allergy and hay fever
  • Available as oral, aerosol and drops
  • Potential toxicities o fcromolyn and nedocromil:
  • Cromolyn–infrequent laryngeal edema, cough, and wheezing
  • Nedocromil–unpleasant taste
18
Q

Treatment of all types of asthmatic patients

A

Mild:

  • > 80% FEV1
  • SABA when needed

Moderate

  • 50 to 79% FEV1
  • one or more bronchodilators + Inhaled GC (IGC)

Severe

  • 30 to 49%
  • one or more bronchodilators + Inhaled GC (IGC) + antibiotic

Very severe

  • <30 or chronic respiratory failure symptoms
  • one or more bronchodilators + Inhaled GC (IGC) + antibiotic + assisted vent
19
Q

MNEMONIC FOR ASTHMA MEDICATION FOR EXACERBATIONS

A
  • Albuterol / Pirbuterol / Terbutaline Steroids
  • Theophylline
  • Humidifier O2
  • Magnesium (severe exacerbations) –when Beta2- agonist and anti-cholinergics are unsuccessful; or Heliox (mixture of 79% helium and O2 21%) inhalation…
  • Anticholinergics
20
Q

Determine the severity of COPD with FEV1 and treatment choices

A
21
Q

MNEMONIC FOR COPD Treatment:

A
  • Corticosteroids
  • Oxygen
  • Prevention (cigarette smoking cessation, infection control; pneumococcal and influenza vaccine)
  • Dilators (anticholinergics and β2–agonists)
22
Q

N-acetylcysteine (abbreviated NAC) –cough:

A
  • It is a used primarily as a mucolytic agent and in the management of acetaminophen overdose.
  • Useful in cystic fibrosis (CF). Breaks disulfide bonds in mucus and liquefies it making it easier to cough out.
23
Q

RHINITIS AGENTS:

A
  • Cromolyn sodium
  • Antihistamines
  • α- Adrenergic agonists
  • Corticosteroids commonly used to treat chronic rhinitis:
  • Beclomethasone and flunisolide.
  • Chronic rhinitis does not show improvement until 2 weeks after the start of therapy.
24
Q

Commonly used antihistamines in the treatment of rhinitis are:

A
  • Diphenhydramine, Chlorpheniramine, Cyproheptadine –they cross BBB and produce drowsiness.
  • Loratadine (Claritin); Fexofenadine (Allegra); Cetirizine (Zyrtec) are non-drowsy antihistamines
25
Q

Mechanism of action of α-adrenergic agonists:

A
  • Phenylephrine and pseudoephedrine
  • Phenyephrine is also used to dilate pupil and to ↑BP
  • Effects of prolonged use of nasal decongestants:
  • Rebound nasal congestion often occurs after discontinuation from prolonged use.
26
Q

Dextromethrophan

A
  • Mechanism of action of dextromethorphan :
  • It suppresses the response of the cough center, but it does not have any analgesic or addictive potential and is less constipating than codeine.
27
Q

Adverse effects of systemic corticosteroids such as prednisone:

A

abnormalities in glucose metabolism, increased appetite, weight gain, hypertension, and adrenal suppression, PUD

• These symptoms can be minimized by limiting systemic therapy to few days.

Pharm S2015 (47 decks)

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