Transcript Drugs for respiratory system

Drugs for Respiratory System
Learning Objectives
At the end of this session, you will be able to:
1．Classify the drugs and typical agents used in
asthma
2．Analyse the mechanism of action,
pharmacological effects, clinical use and adverse
reactions of anti-asthmatic drugs
3．Demonstrate the pharmacological effects,
clinical use and adverse reactions of antitussives
4．Analyse the pharmacological effects, clinical use
and adverse reactions of Expectorants.
Introduction
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Symptoms of respiratory system:
no sputum---antitussives
■
Cough
咳
■
sputum --- expectorants
痰
wheeze ----- antiasthmatic drugs
喘
Global Initiative for Asthma (GINA), 2014
Asthma
由于哮喘和医
生的束手无策
而死于维也纳
Beethoven
1770-1827




Avoid troublesome symptoms during day and night
Need little or no reliever medication
Have productive, physically active lives
Have normal or near normal lung function
Global Initiative for Asthma (GINA), 2014
David Beckham
完
美
情
人
性
感
女
神
Sharon Stone
Gregory
Louganis
柯受良
谢霆锋
郑秀文
杜德伟
朱孝天
陆文夫
张敬轩
Asthma
Pathophysiology:
• Asthma is a disease characterized by
airway inflammation and episodic,
reversible bronchospasm.
• Two characteristic features:
1)
2)
Inflammatory changes in the airway;
Bronchial hyperreactivity to stimuli.
• Important mediators: histamine,
Leukotrienes(LTs, e.g. LTC4, LTD4, etc.)
Drug actions on bronchiolar smooth muscle
Antiasthmatic Drugs
Bronchodilators
I.
1.
2.
3.
β-receptor agonists
Theophylline
Muscarinic (cholinergic) antagonists
Anti-inflammatory agents
II.
1.
2.
Steroids
Anti-leukotriene agents
Anti-allergic agents
III.
1.
2.
Stabilizer of inflammatory cell membrane
H1 receptor blocker
Bronchodilators
Beta Adrenoceptor Agonists
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Epinephrine : α,β agonist
Isoprenaline：β1 ,β2 agonist
Ephedrine (麻黄碱） : α,β agonist
β2 selective agonist
发汗散寒，宣肺平喘
Beta Adrenoceptor Agonists
β2-selective agonists
• Salbutamol(Albuterol ，舒喘灵):
• Terbutaline(特布他林，博利康尼) :
• Bambuterol (班布特罗, 帮备 )
• Pirbuterol 吡布特罗
• Salmeterol(沙美特罗):
long-acting
• Formoterol (福莫特罗):
Mechanism of action
The stimulation of β2-adrenoceptors
leads to an increase production of
cAMP by activating adenyl cyclase.
Route of administration
Inhaled.
 Oral administration is reserved for
children and people unable to use
inhalers.
 Intravenous administration for status
asthmaticus.

Clinical applications
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Acute asthma
Symptom relief during maintenance
therapy of asthma and other conditions
with reversible airways obstruction
(including COPD and bronchitis)
Protection against exercise-induced
asthma
Long-acting β2-selective agonists appear
to interact with inhaled corticosteroids to
improve asthma control.
Adverse Reactions of β2 agonists:
1) Skeletal muscle tremor
2) Cardiac effect: tachycardia
3) Metabolism disturbance:
ketone bodies↑, acidosis, hypokalemia
Clenbuterol
increases the
muscle-to-fat
body ratio
makes its illegal
use in livestock
popular to
obtain leaner
meats.
Theophylline
Mechanism of Action
（none has been firmly established.）
1.
2.
3.
4.
Inhibit phosphodiesterase (PDE);
Block adenosine receptors;
Enhancement of histone deacetylation.
strengthen the contractions of
isolated skeletal muscle in vitro and
improve contractility and reverse
fatigue of the diaphragm.
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Clinical Use:
1. Asthma: maintenance treatment
2. Chronic obstructive pulmonary disease
(COPD)
3. Central sleep apnea (CSA)
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Adverse Reactions:
Narrow margin of safety. Toxic effects are
related to its plasma concentration.
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•
•
Gastrointestinal distress, tremor, and CNS
excitation.
Acute toxicity: cardiac arrhythmias,
convulsions(惊厥) → lethal.
rhabdomyolysis
Muscarinic Antagonists
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There are M1, M2, M3 receptor subtypes in
the airway.
Selectively blocking M1, M3 receptor is
resulted in bronchodilating effect.
Ipratropium bromide binds to all M-R
subtypes (M1, M2 and M3 ), and inhibits
acetylcholine-mediated bronchospasm.
Ipratropium bromide
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Inhalation for the treatment of obstructive
lung diseases.
Ipratropium is also combined with
salbuterol for the management of chronic
obstructive pulmonary disease (COPD)
and asthma.
Anti-inflammatory
Agents
Glucocorticoids (GCs)
Mechanism of Action:
1. Broad anti-inflammatory efficacy
2. Increase the responsiveness of βadrenoceptors in the airway.
Routes of administration:
• Systemic administration: including oral
and injection. More severe toxicity.
Reserved for patients who require urgent
treatment.
• Inhalation: regular or “controller” therapy.
Common inhalant GCs:
• beclomethasone, budesonide
Clinical applications
GCs is limited to selected patients
whose conditions cannot be controlled
with bronchodilators and other nonsteroid
medications.
Adverse reaction
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Systemic reaction.
Inhalaed corticosteroids may cause
oropharyngeal candidiasis and
hoarseness (effect on vocal cords).
邓丽君因过分注意维护自己的完美形象，而没有
遵循哮喘的规范治疗，终因哮喘急性发作又正巧
用完了急性缓解药物于1995年5月8日，猝逝于
泰国清迈。（1953－1995）
Anti-allergic Agents
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Madiators release inhibitors.
Prevent bronchoconstriction caused
by a challenge with antigen.
Cromolyn Sodium
Mechanism of Action:
1. Stabilizer of mass cell membrane:
decreases the release of mediators from
mast cells.
2. Decreases bronchial hyperreactivity
induced by stimuli.
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an inhaler for preventive management
of asthma
Ketotifen
▲ H1
receptor blocker.
▲ Prevent
and inverse down-regulation
of β2-receptor.
Anti-leukotriene agents
Cysteinyl leukotrienes is an important
inflammatory mediator:
• Bronchoconstriction, increased bronchial
reactivity, mucosal edema, mucus
hypersecretion, etc.
• LTD4 receptor antagnist:
zafirlukast and montelukast
• 5-lipoxygenase inhibitor: zileuton
Anti-leukotriene agents
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Used for the maintenance treatment
of asthma
it is not useful for the treatment of
acute asthma attacks
迷走神经兴奋
Ach
（ -）
3. 抗胆碱药
抗原
过敏
反应
（ -）
5. 抗过敏药
ATP
M胆碱受体
cGMP
支气管
收缩
过敏
介质
喘
（LT、组胺、
5-HT）
（ -）
腺苷酸
环化酶
cAMP
毛细血
管扩张
磷 酸
5’AMP
二酯酶
（ -）
受体
A，NA
（ -）
4. 皮质激素
1. 受体激动药
2. 茶碱类
ANTITUSSIVES
▲
Antitussives are drugs that inhibit
the cough reflex.
Cough is usually a valuable protective reflex
mechanism for clearing foreign material and
secretions from the airway.
In some conditions, such as inflammation or
neoplasia, the cough reflex may become
inappropriately stimulated and in such cases,
antitussive drugs may be used.
ANTITUSSIVES
Classification:
Ⅰ Central antitussives
1.
2.
Dependent central antitussives
Independent central antitussives
Ⅱ Peripheral antitussives
Dependent Central Antitussives
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Opioid alkaloids.
Morphine is the most effective drug for the
suppression of cough, but have addiction.
Mechanism: suppressing of cough center
Clinical use: analgesic，sever cough
without sputum (lung cancer) .
Codeine (Methylmorphine)
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Selectively suppress cough center in
medulla oblongata. It is less potent than
morphine and has a correspondingly lower
dependence-liability than morphine
Potency:
• Suppression of cough: ≈1/4 of morphine
• Analgesia: ≈1/7 of morphine
• Respiratory depression, constipation, tolerance,
dependence ＜ that of morphine
Pharmacokinetics:
• Well absorbed from oral and injection.
• 10% converted to morphine through
demethylation.
Clinical Uses:
• Dry cough, a painful cough caused by
pleurisy will be controlled with codeinebased cough syrups
Codeine
Adverse Reactions:
• Respiratory suppression in high dose
(asphyxiation);
• Tolerance and physical dependence with
frequently repeated administration;
• Suppress secretion of bronchial gland
and movement of cilia.
Cough syrups and tablets containing
codeine are available without
prescription;
Some potential recreational users are
reported to buy codeine from
multiple pharmacies
Independent Central Antitussives
dextromethorphan(右美沙芬)
Stereoisomers of opioid molecules
that are devoid of analgesic effects
and addiction liability.
pentoxyverine(喷托维林;咳必清）
cloperastine(氯哌斯汀)
Dextromethorphan（右美沙芬）
Clinical Use:
• Dry cough. Often + Antihistamine drug
• Because administration of
dextromethorphan can trigger a
histamine release (an allergic reaction),
its use in atopic children is very limited.
Pentoxyverine(喷托韦林）
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Suppression of cough: ≈1/3 of
codeine.
Direct suppression of cough center
Atropine-like action and local
anesthetic action.
Cloperastine
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Derivative of diphenhydramine(苯海拉
明).
Suppression of cough center
Blocking H1-receptor
Peripheral Antitussives
Reduce the sensitivity of peripheral
sensory ‘cough receptors’.
1. Local anesthesia action: narcotine(那可
丁), benzonatate(苯佐那酯);
2. Alleviative action: extractum
glycyrrhiza liquidum(甘草流浸膏),
Syrup(糖浆)
Expectorants
1. Mucus secretagogue drugs:
stimulating gastric mucosa → reflex
secretion of bronchial gland↑ →
dilution of sputum.
Ammonium chloride.
Guaifenesin (愈创木酚甘油醚）
Expectorants
2.Mucolytic drugs:
1)
2)
3)
Acetylcysteine(乙酰半胱氨酸):reduce the
viscosity of bronchial secretions by
cleaving disulphide bonds cross-linking
mucus glycoprotein molecules.
Bromhexine(溴己新; 必嗽平): break acid
mucin:
DNAase: Enzymolysis