TOpic 15, selective b2 stimulants and other bronchodialators Flashcards Preview

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Flashcards in TOpic 15, selective b2 stimulants and other bronchodialators Deck (10):
1

goals of therapy

1. reduce intensity and frequency of symptoms. 2. Relief of acute asthma symptoms. 3. Long term therapy: prevention of inflammation

2

how to treat asthmatic patients

1. Asses the severity of asthma and start the treatment according to the guidelines 2. increase Intensity of treatment stepwise, until the asthma is well controlled 3. reduce dose of anti-inflammatory agents gradually (if possible), to minimize the side effects

3

drugs used in asthma treatment

are:

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4

Short-acting b2 agonists (SABA):

  • Rapid onset (5-30min)
  • Duration: 4-6 hours
  • Symptomatic treatment of acute bronchospasm – inhaler
    • Used as relievers
  • b2 agonists aren’t anti-inflammatory so never use alone
    • Although it may be used as a monotherapy for patients with intermittent asthma or exercise-induced asthma

 

Action:

  • Bronchodilation
  • ­ mucociliary transport
  • ¯ release of inflammatory mediators

 

Adverse effects:

  • Cardiovascular disturbances (Tachycardia, palpitation, angina)
    • Direct cardiac effect (b1, b2)
    • Vasodilation (b2)
    • Presnaptic norepinephrine release (b2)
  • Hypokalemia
  • Metabolic effects: Hyperglycemia, hyperlipidemia
  • Hypomagnesemia
  • Skeletal muscle tremors
  • ¯ PaO2
  • Mild loss of appetite, disturbed sleep
  • Development of tolerance

 

Drugs:

  • Albuterol (salbutamol)
  • Levalbuterol
  • Terbutaline
  • Fenoterol

Short-acting b2 agonists (SABA):

  • Rapid onset (5-30min)
  • Duration: 4-6 hours
  • Symptomatic treatment of acute bronchospasm – inhaler
    • Used as relievers
  • b2 agonists aren’t anti-inflammatory so never use alone
    • Although it may be used as a monotherapy for patients with intermittent asthma or exercise-induced asthma

 

Action:

  • Bronchodilation
  • ­ mucociliary transport
  • ¯ release of inflammatory mediators

 

Adverse effects:

  • Cardiovascular disturbances (Tachycardia, palpitation, angina)
    • Direct cardiac effect (b1, b2)
    • Vasodilation (b2)
    • Presnaptic norepinephrine release (b2)
  • Hypokalemia
  • Metabolic effects: Hyperglycemia, hyperlipidemia
  • Hypomagnesemia
  • Skeletal muscle tremors
  • ¯ PaO2
  • Mild loss of appetite, disturbed sleep
  • Development of tolerance

 

Drugs:

  • Albuterol (salbutamol)
  • Levalbuterol
  • Terbutaline
  • Fenoterol

5

what are the LABA drugs

Albuterol (salbutamol)

Levalbuterol

Terbutaline

Fenoterol

6

Long-acting b2 agonists (LABA):

Long-acting b2 agonists (LABA):

  • Slower onset of action
  • Duration: 12 hours
    • Higher lipophilicity è accumulation in membranes
  • Not used for quick relief of an acute asthma attack, but rather as controllers in patients with moderat/severe asthma and COPD
  • Never used as a monotherapy.
    • Only used in a combination with asthma controlling-medication
      • Inhaled corticosteroids (main choice)
      • Synergistic effect: Small dose of steroid + LABA is stronger than a high dose of steroid

 

Action:

  • Bronchodilation

 

Adverse effects:

  • Same as SABA

 

Drugs:

  • Salmeterol (=albuterol)
    • Partial agonist
  • Formoterol
    • Faster onset of action
  • Clenbuterol
    • Oral agent
  • Bambuterol (® Terbutaline)
    • Oral agent
  • Indacaterol, olodaterol, vilanterol
    • Duration > 24h (VLABA)

7

what are the LABA drugs

Drugs:

  • Salmeterol (=albuterol)
    • Partial agonist
  • Formoterol
    • Faster onset of action
  • Clenbuterol
    • Oral agent
  • Bambuterol (® Terbutaline)
    • Oral agent
  • Indacaterol, olodaterol, vilanterol
    • Duration > 24h (VLABA)

8

Theophylline (xanthine)

Other bronchodilators:

Xanthines:

  • Other xanthines with no bronchodilator effect: caffeine, theobromine
  • Theophylline:
    • It gives rise to aminophylline
    • Therapeutic effect:
      • Bronchodilation
        • decrease a1 receptor
        • decrease PDE3 [phosphodiesterase] è ­ cAMP
      • decrease Release of inflammatory mediators
        • ¯decrease PDE4
        • decrease a1 receptor
        • ­ HDAC2
      • increase­ Ciliary activity
    • Side effects:
      • ­ CNS
        • Anxiety
        • Insomnia
        • Tremor
        • Seizures
      • Cardiovascular:
        • At low doses, mild elevation of BP (a receptor decrease)
        • At higher doses, “inodilator” effect (­ cAMP)
      • Diuretic effect
        • increase­ GFR
        • decrease Tubular sodium resorption
      • ­ Gastrointestinal secretions increase
        • Gastric acid
        • Digestive enzyme

 

  • Pharmacokinetics:
    • Good oral absorption
    • Narrow therapeutic index

  • Clinical use:
    • Prevention of asthmatic attack (oral, extended-release tablets)
    • Reliever in acute asthma (aminophylline IV)

 

9

MaChR antagonists?

mAChR antagonists:

  • Mechanism of action:
    • M3 is present in bronchial smooth muscle cells (they normally cause contraction)
    • We use only drugs having a quaternary nitrogen nowadays because:
      • Plasma concentration stays low
      • The drugs don’t enter CNS
  • Therapeutic effects:
    • Bronchodilation
    • decrease Bronchial secretions
    • Block vagally-mediated contraction of airway smooth muscle and mucus secretion
  • Clinical use:
    • Relievers (ipratropium) or controllers in asthma and COPD
      • Used adjacent to b2 agonists
      • Instead of b2 agonists, if those are contraindicated or not tolerated
      • If cholinergic tone is elevated (e.g. nocturnal asthma)
      • Patients with concomitant COPD
      • Asthmatic attack – alternative or add-on drugs for SABA
      •  
  • Adverse effects:
    • Dry mouth
    • Cough
  • Drugs:
    • Atropine
    • Ipratropium
      • Non-selective muscarinic receptor antagonist
      • Onset: < 15min
      • Duration: 4-6h
      • Administration: 3x/day
    • Tiotropium, glycopyrronium, aclidinium, umeclidinium
      • Selective for M3 receptors (slower dissociation)
      • Longer effect: T1/2 = 11h - 6 days (except aclidinium)
      • Administration: 1x/day

10