Drugs Affecting the Respiratory System

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Drugs Affecting the Respiratory System

• By
• Caiying Ye
• Department of Pharmacology, School of Basic
  Medicine, Peking Union Medical College

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Introduction

• Antiasthmatics ???
• Antitussives ???
• Expectorants ???

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??

• ?????????????????,?? ??????????
• ????????,?????????
• ?????????,?????.
• ???????????????,?????,????,????????????

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??? Antiasthmatic Drugs
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Aasthma

• A chronic inflammatory disease of the airways
• Clinical feature bronchospasm, bronchial
  obstruction, dyspnea
• Pathologic changeslymphocyte infiltration,
  mucosal oedema, vascular leakage, airway smooth
  muscle proliferation.
• Cellular infiltration invovling mast cell and
  eosinophil triggers bronchial inflammation and
  allergic response in susceptible population.
• Treatment principleinhibit airway inflammation
  and inflammatory mediators.

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Classifications

• ß2 adrenoceptor agonists
• Methylxanthinesaminophiline ???
• Muscarinic antagonists ipratropium bromide?????
• Glucocorticosteroids beclomethasone
  dipropionate??????
• Mast cell stablizers sodium cromoglicate????

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Effect of antiathmatic drugs on intracellular
levels of cAMP
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1. Adrenoceptor agonists
Nonselective Epinephrine ????(Adrenalin) Ephedirine ??? Isoprenaline ??????
ß2 agonist Salbutamol ????(albuterol ???) Terbutaline ????(Breathair) Clenbuterol ???? Formoterol ???? Bambuterol ????
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1. Adrenoceptor agonists

• ????
• Activate ß2 receptor
• activate adenylyl cyclase cAMP
• Ca2 relax airway smooth muscle
• Activate a receptor
• cause vasoconstriction reduce
  edema
• improve airflow
• dilate the bronchus to relieve bronchospasm
• Activate ß receptor on the membrane of mast cell
  inhibit release of allergic mediators
  prevent allergic asthma attack

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• ????
• ????????,?????????????ß 2??????,????,??????,?????
• ?????????????,???????????????

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• ???? adrenaline,epinephrine
• ?????????
• Stimulate a, ß1 ß 2 receptors
• ß???????
• a????????????,????,???????
• ????ß1??,??????.
• ???a?????,?????????,??????.
• ????,??????,???????

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• ???ephedrine
• ???????,?????,????,??,??4-6??
• ???????????,?????
•  
• ??????isoprenaline (???)
• ??????( Stimulate both ß1 ß 2 receptors )
• ????,1 min??????,??1-2 hr
• ?????????,?????

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????salbutamol(???)

• ??
• ?ß 2??????ß1??,???????
• ???????????,????
• ???????????????????????????????

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2. theophylline ??? aminophylline
???cholinophylline

• Pharmacologic effects
• Relaxes airway smooth muscle
• Improves respiratory function
• Positive inotropic effect

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• Mechanism of relaxing airway smooth muscle
• ? Inhibits phosphodiesterases,leading to
  intracellular accumulation of cAMP and smooth
  muscle relaxation.
• ?Stimulates endogenous epinephrine noradrenalin
  release, relaxing airway smooth muscle.
• ?Blocks adenosine receptor, antagonizing
  bronchial constriction induced by endogenous
  adenosine.

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• Improves respiratory function
• enhancing diaphragmatic contraction,?????????
  ,???????,????????
• Positive inotropic effect???????,??????,?????????
  ,????????????????????,?????????

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Therapeutic uses

• Acute or chronic asthma,cardiac asthma(?????)
• Chronic obstructive pulmonary disease(????????)
• Cardiac edema renal edema (???????)

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Adverse effects

• Gastrointestinalnausea, vomiting
• Cardiovascularpalpitation (??),arrhythmias(????),
  ??,????????????,???????

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3. Muscarinic antagonists

• ??M??()??????cGMP??,???????????,????????,????? 

parasympathetic neurons
M 1 and M3 receptors
Ach
Mucus gland secretion increases Airway smooth
muscle cell contracts
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Muscarinic antagonists

• ????? ipratropium bromide
• ??
• ????????????
• ??????
• ??????????

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4. Glucocorticoids

• The best established anti-inflammatory drugs for
  the treatment of asthma.
• Glucocorticoids produce significant
  anti-inflammatory, immunodepressive and
  anti-shock effect, probably by attenuating
  prostaglandin and leukotriene synthesis,
  preventing release of inflammatory mediators and
  decreasing mucus production.
• Glucocorticoids are usually reserved for patients
  with severe persistent asthma.
• Inhaled glucocorticoids achieves a significant
  anti-inflammatory effect without causing systemic
  adverse effects.

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?????? beclomethasone

• (????????)
• ?????????
• ????,???????,????
• ???,NOT for acute asthmatic attacks!
• ???????oral fungal infections(??????)?

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5. Mast Cell Stabilizer

• Cromolyn Sodium ????
• (Nasalcrom,Intal)
• Ketotifen ???
• Nedocromil Sodium ?????(Tilade)

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Pharmacologic Effects and Mechanism

• ????????,????????????(inhibits chloride channels
  and inhibits the release of histamine and other
  autacoids from mast cells)
• ???????????????? (depress the exaggerated
  neuronal reflexes triggered by irritant receptors
  in the airways)

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Pharmacologic Effects and Mechanism

• ??????????????(bronchial hyperreactivity)
  ????????????????????????,????????????????

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Therapeutic Uses

• (1) ?????,???????
• (2) ??????????
• (3) ??????
• (4) ???????????
• (5) ???????

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Adverse Effects

• (1)?????????,??????
• (2)??????,??,??,??,????

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??? Expectorants
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??? Expectorants

• ???(expectorants)
• ???????,?????????????,??,??????,???????????
  ???
• ?????
• ?????????,?????????????????

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??? Expectorants

• ???????????
• ???????,????????
• ? ??????????????

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??? Expectorants

• 1.???????
• ammonium chloride ???
• guaifenesine ???????
• potassium iodide ???
• ipecac syrup ????
• ?????????????
• 2.Mucolytics ?????
• acetylcysteine ??????,???
• bromhexine ???,???

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Classification of Mucolytics

• (1) ??????????????? ???????????
• (2) ??????????????????,??????????????????????????
  ?
• (3) ???
• (4) ?????????

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???ammonium chloride

• ?????,?????,??????????,????,???
• ?????????
• ????????????????
• ??????????????????????????

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?????? Acetylcysteine (???)

• ??????N-????,??????????????????,?????????????,????
  ????,?????
• ?????????????????
• ????????,???????,??????

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?????? Acetylcysteine (???)

• ?????,???????,????????,???????????????????
• ??????(penicillin)?
• ????(cephalosporin)?
• ???(tetracycline)??,??????????

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???(Antitussives)
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???(antitussives)

• ???????,?????????, ?????,??????
• Two Basic Types of Cough
• Productive Cough Non-Productive
  Cough
• Congested cough Dry/Hacking
  cough
• removes excessive self-feed
• secretions
• DONT USE USE
  ANTITISSIVES
• ANTITUSSIVES

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???(antitussives)

• Central antitussives
• Narcotic ???(Opioids ???)
• codeine ???
• Non-narcotic ????(Non-opioids ????)
• dextromethorphan ????
• pentoxyverine ????,???
• Peripheral antitussives
• benzonatate ????

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??? codeine

• Strongly effective cough suppressant, 1/4
  morphine
• Use for dry cough
• Produce constipation, nausea and respiratory
  depression (60 mg).
• Addictive liability
• Rarely recommended for children.
• NOT for cough accompanied with excessive
  secretions.

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Dextromethorphan ????

• The most popular antitussives
• Selectively depresses the cough center in the
  medulla
• 1530 mg 815 mg codeine as an antitussive
• Therapeutic effect dry cough
• No respiratory depression, no euphoria and
  physical dependence
• Adverse effects are mild and rare dizziness,
  drowsiness, nausea

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??? pentoxyverine

• Selectively depresses the cough center, 1/3
  codeineatropine-like effect local anesthetic
• ?????????????????????????
• Therapeutic effect dry coughgood for children
• ??????

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Peripheral Antitussives

• ??? narcotine
• ???? benzonatate
• ???????????????????,??????????

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Thanks!