DRUGS ACTING ON THE

RESPIRATORY SYSTEM

Dr. Ragia M.Hegazy

MD CLINICAL TOXICOLOGY

Assistant professor of clinical toxicology

Faculty Of Pharmacy,

Umm Al-Qurra University

Drugs of resp. syst

Mucoactive agents

1-Expectorant

2-Mucolytics

3-Mucokinetics

4-Mucoregulatory agents

5-Others

Cough suppressants (antitussives)

1-Peripheral antitussives

2-Central antitussives(narcotic or non narcotic)

3-Central & peripheral antitussives

Respiratory Stimulants (analeptics)

1-Specific analeptics

2-Non-specific analeptics

MUCOACTIVE AGENTS

Types of cough

1. Use cough: productive treated by mucoactiveagents (expectorants, mucolytics, etc)

2. Useless cough: dry, non-productive not associated with sputum and treated by

antitussive

Mucoactive agents (dry cough ttt)

Are agents that help in airway clearance

They serve the purpose of either:

increase the ability to expectorate sputum

or

decrease mucus hyper-secretion

Mucoactive

agents

1-Expectorant

increase volume or hydration of airway

secretion

2-Mucolytics

1-classic mucolytics(NAC- L-cysteine)

2-SCMC

3-Proteolytic enzymes

3-Mucokinetics

stimulating

ciliary activity

1-Bronchodilators

2-Ipratrobium

3-Abhesives

4-Mucoregulatory

agents

1-Anti- inflam

2-Anticholinergic

3-Macrolide antibiotics

5-Others

1-Ambroxol

2-Saline

3-Na HCO3

Classification according to mechanism

of action

1-Expectorants: increase volume or

hydration of airway secretion

Systemic hydration no clinical effect

Classic expectorants no clinical effect

Modifier of airway water transport (being

investigated)

2-Mucolytics: degrade polymers in secretion

A. Thiols with free sulphydryl groups (classic mucolytics)

N- Acetyl Cysteine (NAC):

Disrupts disulfide bond making mucus less resistant

NAC can be taken orally, inhalation or instillation

Side effects:

1) GIT irritation (oral)

2) Burning sensation in airways (inhalation)

3) Bronchospasm (inhalation)

4) Sulphorous taste & odor (inhalation)

L-cysteine ethyl ester hydrochloride:

Given orally

Biotransformed in liver to NAC

Used in COPD

Has no GIT side effects

B. Thiols with blocked sulphydryl group

S- caboxymethyl cysteine (SCMC)

Does not break mucin disulfide bonds

Increases nasal mucociliary clearance in chronic sinusitis (not

in chronic bronchitis

C. Proteolytic enzymes (peptide enzymes)

They increases sputum viscidity

3-Mucokinetics: increase mucociliary efficiency or cough efficiency

Bronchodilators: they increase cough flow in patients with airway hyperactivity e.g. b2 agonist & theophyllineciliostimulant and bronchodilator

Ipratropium bromide has no anti-mucokinetic

Abhesives: such as surfactants

Pharmacological action Decrease mucus attachment to cilia and epithelium

Increase cough and mucociliary effect

Mucoregulatory agents: decrease the volume of airway mucus secretion

Effective in hypersecretory states (bronchorrhea and

bronchial asthma)

A. Anti-inflammatory agents: Iidomethacin &

corticosteroids

B. Anticholinergic agents

C. Macrolide antibiotics: erythromycin, clarithromycin,

and azithromycin

Long-term oral administration causes decrease in water and mucus secretion in airway

5- Other muco-active agents

A. Bromohexine & Ambroxol

Bromohexine increases expectoration of sputum in chronic bronchitis

Ambroxol stimulates mucus secretion and causes normalization of mucus viscosity in viscid secretion

B. Saline solution (isotonic, 0.9%) water causes Bronchospasm

Uses:

For routine nebulisation therapy

Hydration of mucus

C. Sodium bicarbonate (2%): alkaline environment causes decrease in mucus elasticity

If mucus secretion increases, viscidity decreases

Therapeutic uses of Mucoactive agents :

1. Respiratory mucostasis e.g. chronic bronchitis,

asthma & cystic fibrosis

2. Chronic sinusitis (+ antibiotics)

3. With antibiotics for treatment of airway infections

e.g. bronchiectasis

4. Prophylaxis of post-operative chest complications

5. Sputum production for diagnostic purposes e.g.

T.B.

COUGH SUPPRESSANTS

(ANTITUSSIVES)

Types of cough

1. Use cough: productive treated by mucoactiveagents (expectorants, mucolytics, etc)

2. Useless cough: dry, non-productive not associated with sputum and treated by

antitussive

Cough suppressants (antitussives)

Antitussives are drugs used in the treatment of dry

cough to suppress it (reduce input of stimuli arising

from pharynx, larynx & trachea). They include:

1- Peripheral antitussives

e.g. Liquorice, steam inhalation of tincture benzoincomposite and menthol

They have soothing effect on the irritant mucus membrane

2- Central antitussives

They inhibit the cough center

May be narcotics or non-narcotics

Narcotic antitussives:

Codeine & morphine: antitussive, analgesic, euphoric,

respiratory center depression & dependence

Pholcodeine and hydrocodone: weak addictive,

analgesic, euphoric & respiratory center depression

Non-narcotic antitussives:

1. Noscapine (natural opium alkaloid)

2. Dextromethorphan

Have no analgesic effect

No dependence

No euphoria

No respiratory center depression

3-Central & peripheral antitussives

Benzonatate

They inhibit cough center

They inhibit pulmonary stretch receptors

Antitussives

Peripheral antitussives

1-Liquorice lozenges,

2- steam inhalation of tincture benzoin

3-menthol

Central antitussives

1-Narcotic antitussives:

Codeine, Pholcodeine

2-Non-narcotic antitussives:

Noscapine

Central & peripheral antitussives

Benzonatate

RESPIRATORY STIMULANTS

(ANALEPTICS)

Respiratory Stimulants

(analeptics)

1-Specific analeptics

Naloxone with opiate toxicity

Flumazenil with BDZ toxicity

2-Non-specific analeptics

1-Direct brainstem stimulants e.g. xanthines (Theophylline)

2-Reflex brainstem stimulants Nicotine

3- Direct & reflex e.g. Doxapram

Respiratory Stimulants (analeptics)

They are drugs stimulating the CNS especially the

brainstem. They include:

1- Specific analeptics: used when respiratory

depression is due to certain drug overdose e.g.

Naloxone with opiate toxicity

Flumazenil with Benzodiazepine toxicity

2-Non-specific analeptics:

A. Direct brainstem stimulants e.g. xanthines

(Theophylline)

B. Reflex brainstem stimulants through stimulation of

chemoreceptors in carotid bodies & aortic arch e.g.

Nicotine

C. Direct & reflex e.g. Doxapram

Therapeutic uses of analeptics:

1. Treatment of respiratory center inhibition

2. Treatment of cerebral cortex inhibition

Adverse effects of analeptics:

1. Tachycardia

2. Tachpnea

3. Hypertension

4. Toxic dose causes convulsions

Contraindications of analeptics:

1. Epilepsy

2. Ischemic heart disease

3. Hyperthyroidism

4. Hypertension

WHAT ARE THE DRUGS ACTING

ON THE RESPIRATORY

SYSTEM????

What categories of drugs are used as

bronchodilators

Beta agonists

Methylxanthine derivatives

Anticholinergics

Which nonselective beta agonist is

most effective as a bronchodilator

Isoprenaline (isoproterenol)

Why are beta 2 agonists the best

drugs for bronchial asthma

Bronchodilator

And decongestant, anti-inflammatory, and

increases mucociliary clearance

What are the side effects of beta

agonists as bronchodilators

Tachycardia **

Hypotension

Hyperglycemia

Hypokalemia

Muscle tremors

Uterine relaxation

what is the clinical use of

leukotriene inhibitors

Orally for prophylaxis and chronic tx of

bronchial asthma in humans

Montelukast, & Zafirlukast

Zilleuton used to be used but not anymore

because it increases liver enzymes

What is the mechanism of action of

antihistamines in BA

Act by competitive antagonism to H1

receptors

What are uses of antihistamines

Chronic resp disease because of their effects

on the bronchial secretions

Not useful in the control of asthma

What are antitussives

Decrease the frequency and severity of

nonproductive cough without impairing

mucociliary defenses

What drugs are narcotic antitussives

Codeine

Hydrocodone

Morphine

Are the narcotic antitussives

centrally acting or peripherally

acting?

Centrally acting

What are the non narcotic centrally

acting antitussives

Dextromethorphan

Noscapine

What are the peripherally acting

antitussives

Bronchodilators

Mucokinetics

What are mucokinetic drugs

Drugs that facilitate the removal of secretions

from the resp tract

What is the mechanisms of action of

mucokinetic drugs

Act by stimulating ciliary action

Act by decreasing viscosity of bronchial

secretions

Which mucokinetic drugs act by

stimulating ciliary activity

Beta agonists

Methylxanthines

Which mucokinetic drugs act by

decreasing viscosity of bronchial

secretions Hydration

Saline, sterile water

Increasing pH

Bicarb

Breaking the disulfide linkages in the mucus

Acetylcysteine

What is another use for

acetylcysteine

Antidote for APAP toxicity

What are expectorants

Drugs which increase the volume and fluidity

of resp secretions

What are the mechanisms of action

of expectorants

Act reflexly by irritation of gastric mucosa

Cause direct stimulation

What is the classification

decongestants

Vasoconstrictors Phenylephrine, oxymetazoline, xylometazoline,

naphazoline) ( 1 agonist), ephedrine ( & agonists

), pseudoephedrine, phenylpropanolamine (norephedrine

and oxyamphetamine)

H1 antagonists

Diphenhydramine, hydoxyzine, chlorpheniramine,

promethazine, cyproheptadine

Cromolyn sodium (intal)

Glucocorticoids