Download Drugs for Respiratory System

Drugs for Respiratory System
GAO Fen-Fei
Introduction

Symptom of respiratory system:
no sputum---antitussives

Cough
sputum --- expectorants

Asthma ----- antiasthmatic drugs
支气管痉挛、
粘膜水肿
平喘药
喘息
管腔狭窄
阻塞细支气管
继发感染、加重症状
呼气阻力增加
排痰困难
呼吸道积痰
刺激气管粘膜
咳嗽
排痰
镇咳药
祛痰药
ANTITUSSIVES

Classification:
一．Central antitussives
1.
2.
Dependent central antitussives
Independent central antitussives
二．Peripheral antitussives
Dependent Central Antitussives



Opioid alkaloids.
Morphine is the most effective drug
for the suppression of cough, but
have addiction.
Mechanism: suppressing of cough
center
Codeine


Selectively suppress cough center in
medulla oblongata(延髓).
Potency:
• Suppression of cough: ≈1/10 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 demethyl.

Clinical Uses:
• Dry cough

Adverse Reactions:
• Respiratory suppression in high dose;
• Tolerance and physical dependence with
frequently repeated administration;
• Suppress secretion of bronchial gland and
movement of cilia.
Independent Central Antitussives


Stereoisomers of opioid molecules that are
devoid of analgesic effects and addiction
liability.
Classification:
1) -orphan(吗啡南类)-antitussives :
dextromethorphan(右美沙芬)
2) Amido(胺基)-antitussives: pentoxyverine(喷托维林;
咳必清), clofedanol(氯苯达诺;敌退咳)
3) piperidine(哌啶基)-antitussives: cloperastine(氯哌斯
汀)
4) morpholine(吗啉基)-antitussives: promolate(普罗吗
酯), fominoben(福米诺苯);
5) Others: eprazinone(依普拉酮), zipeprol(齐培丙醇).
Dextromethorphan


Dextrorotatory stereoisomers of a
methylated derivative of
levorphanol(羟甲左吗南).
Clinical Use:
• Dry cough. Often + Antihistamine drug
Pentoxyverine



Suppression of cough: ≈1/3 of
codeine.
Direct suppression of cough center
Atropine-like action and local
anesthesia action.
Cloperastine



Derivative of diphenhydramine(苯海拉
明).
Suppression of cough center
Blocking H1-receptor
Peripheral Antitussives

Inhibiting receptor, afferent nerve,
efferent nerve of cough reflex arc →
cough suppression.
1. local anesthesia action: narcotine(那可
丁), benzonatate(苯佐那酯);
2. Alleviative action: extractum
glycyrrhizae liquidum(甘草流浸膏),
Syrup(糖浆)
Expectorants


I.
Mucokinetic drugs
Classification:
By the mechanism of action:
1.
2.
Mucus secretagogue drugs: stimulating
gastric mucosa → reflex secretion of
bronchial gland↑ → dilution of sputum.
ammonium chloride.
Mucolytic drugs:
1)
2)
3)
4)
break acid mucin: bromhexine(溴己新; 必嗽平)
drug-SH
S-S of mucin → Fragmentation:
acetylcysteine(乙酰半胱氨酸)
Enzymolysis: α-chymotrypsin(糜蛋白酶)
Surfactant: tyloxapol(泰洛沙泊)----Fog inhalation
II. By route of administration：
1.
Oral drugs:
2.
Fog inhalation drugs: 1.8%NaCl,
2%~7.5%NaHCO3.
Asthma

Pathophysiology:
• Asthma is a disease characterized by
airway inflammation and episodic(发作性
的), reversible bronchospasm(支气管痉挛).
• Two characteristic features:
1)
2)
Inflammatory changes in the airway;
Bronchial hyperreactivity to stimuli.
• Important mediators: histamine, LTC4,
LTD4, etc.
Antiasthmatic Drugs
Bronchodilators
I.
1.
2.
3.
β receptor agonists
Theophylline
Muscarinic 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




Adrenaline: α,β agonist
Ephedrine: α,β agonist
Isoprenaline：β1 ,β2 agonist
β2-selective agonists
•
•
•
•
•
•
Salbutamol(沙丁胺醇，舒喘灵):
Terbutaline(特布他林，博利康尼) :
Clenbuterol(克仑特罗):
Formoterol(福莫特罗):
Salmeterol(沙美特罗):
Bambuterol(班布特罗):
intermediateacting
long-acting

Adverse Reactions of β2 agonists:
1) Skeletal muscle tremor
2) Cardiac effect: tachycardia(心悸亢进),
arrhymias
3) Metabolism disturbance: ketone
bodies↑, acidosis, [K+]o↓
Theophylline


Methylxanthine derivatives.
Mechanism of Action:
1. Inhibit phosphdiesterase (PDE);
2. Block adenosine receptors;
3. Increase endogenous catecholamine
(CA) releasing;
4. Interfere with receptor-operated Ca2+
channels → [Ca2+]i↓;
5. Anti-inflammatory action
Clinical Use:

1. Asthma: maintenance treatment
2. Chronic obstructive pulmonary disease
(COPD)
3. Central sleep apnea (CSA)
Adverse Reactions:

•
•
•
Narrow margin of safety. Toxic effects are
related to its plasma concentrations.
Gastrointestinal distress, tremor, and insomnia.
Cardiac arrhythmias, convulsions(惊厥) → lethal.
Muscarinic Antagonists



There are M1, M2, M3 receptor
subtype 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.
Anti-inflammatory
Agents
Glucocorticoids (GCs)

Mechanism of Action:
1. Broad anti-inflammatory efficacy
①
②
Block the synthesis of arachidonic acid(花生
四烯酸) by phospholipase A2.
Reduce bronchial reactivity.
2. Increase the responsiveness of βadrenoceptors in the airway.

Routes of administration:
• Systemic administration: including oral
and injection. More severe toxicity.
• Inhalation:

Common inhalant GCs:
• FP, BDP, BUD, TAA, FNS
Anti-leukotriene agents

Cysteinyl leukotrienes is a important
inflammatory mediator:
• Bronchoconstriction, increased bronchial
reactivity, mucosal edema, mucus
hypersecretion, etc.

Leukotrienes resulte from the action
of 5-lipoxygenase on arachidonic acid.

Common agents:
I. zafirlukast and montelukast:
LTD4-receptor antagonists
II. zileuton: 5-lipoxygenase inhibitor
Anti-allergic Agents


Madiators release inhibitors.
No bronchodialator action but can
prevent bronchoconstriction caused
by a challenge with antigen to which
the patient is allergic.
Disodium Cromoglycate (SCG)

Mechanism of Action:
1. Stabilizer of mass cell membrane:
decrease the release of mediators from
mast cells.
2. Inhibit the function of sensory nerve
ending and neurogenic inflammation in
airway.
3. Decrease bronchial hyperreactivity.
Ketotifen


H1 receptor blocker.
Prevent and inverse down-regulation
of β2-receptor.