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Antitussives and expectorants
• Cough is a protective reflex that removes
foreign material and secretions from the
bronchi and bronchioles.
• Coughing may be initiated either voluntarily or
reflexively
• Two types :
– Productive cough( useful cough)
– Unproductive cough ( useless cough)
Classification
ANTITUSSIVES/COUGH SUPPRESSANTS
a. Opiods and related drugs

•
•
•
•
•

Codeine
Hydrocodone
Pholcodeine
Morphine
Ethylmorphine

EXPECTORANTS
a.
Directly acting:
Sodium and potassium salts of iodine ,
citric acid or acetic acid , guaicol, tolu
balsam, terpene hydrate, Guaiphenesin
b. Reflexly acting :
i)
Saline expectorants : NH4Cl, NaHCO3
ii)
Ipecacuanha syrup

b. Non-opioids
•
Dextromethorphan
•
Caramiphene
•
Noscapine

c. Mucolytics :

c. Antihistamines
•
Chlorcyclizine
•
Diphenhydramine
•
promethazine

Pharyngeal demulcents :
Lozenges, cough drops , linctuses
containing syrup, glycerine , liquorice

i)
ii)
iii)

Bromhexine
Acetylcysteine
Carbocisteine
Specific treatment approach of cough
• Upper respiratory infection:
antibiotics
• Smoking / chronic bronchitis : cessation of
smoking , avoidance of pollutants
• Pulmonary tuberculosis : antitubercular drugs
• Asthmatic cough: antiasthmatics
• Postnasal drip due to sinusitis : antibiotic , nasal
decongestants , H1 blockers
• Gastroesophageal reflux : bed head elevation,
light dinner , diet modification , drugs for PUD
• ACE inhibitor associated cough: substitute by
losartan, indomethacin , nifedipine
1 . MORPHINE
• It is an effective antitussive but it
produces depression of
respiratory centre and drug
dependence .Hence it is not used
at clinical level for antitussive.

2. CODEINE PHOSPHATE
• It is centrally acting cough
suppressant.
MECHANISM OF ACTION
• Depresses cough reflex by a
direct depressant effect on cough
centre .
USES
• Used for dry and painful cough.
• Standard narcotic antitussive
• Severe pain
• Antispasmodic
• Diarrhoea

ADVERSE EFFECTS
•
•
•
•
•
•
•

Nausea
Vomiting
Constipation
Addiction
Drowsiness
Respiratory depression
In case of liver disease ,increased
dose causes convulsions in
children

PRECAUTIONS
• Prostatic hypertrophy
• Hepatic disease
CONTRAINDICATIONS
• In bronchial asthma because it
induces bronchospasm.
• Children below 2 year
DOSE
Mild to moderate pain
Adult dose ::30-60mg every 4
hours ,to a maximum of
240mg daily
Child dose:1-12 years:3mg/kg
daily in divided doses
Dry or painful cough
Adult dose:15-30mg 3-4 times
daily
child dose:7.5-15mg 3-4 times
daily
PHOLCODINE
• It is semisynthetic derivative of codeine.
• It is It is available as linctus and may be given to children ..It
doesnot cause constipation and less liable to cause addiction as
compared to codeine.
• It is more potent than codeine .
MECHANISM OF ACTIONS
• Same as codeine
USES
• For dry and painful cough.
ADVERSE EFFECTS
• Nausea
• Drowsiness
DEXTROMETHORPHAN
• The antitussive activity of the drug is about equal to that of codeine.the
drug produces no analgesia or addiction or CNS depression.And is also
devoid of constipating actions.
MECHANISM OF ACTION
• Acts centrally to elevate the threshold for coughing.
USES
• Widely used anti tussive and is the constituent of many cough remedies.
• Used for dry cough
ADVERSE EFFECTS
It occasionally causes
• Drowsiness
• Dizziness
• Excitation
• Mental confusion
• GI disturbances
CONTRAINDICATIONS
• Liver disease
DOSES
• 10-20mg every 4hrs or 30mg every 6-8hrs
NOSCAPINE
• It is as effective as codeine.
• It has weak bronchodilator properties and stimulates the respiration.
• IT is available as linctus and effect last for 4 hrs.It has no addicting,sedative
and analgesic properties.
ADVERSE EFFECTS
Drowsiness and nausea
DOSE
Adult:15-30mg
CONTRAINDICATIONS
asthma
H1 antihistamines
• Many H1 antihistamines have been added to
antitussive/expectorant formulations .They afford
relief in cough due to their sedative and
anticholinergic actions but lack selectivity for the
cough centre.They have no expectorant
action,may even reduces secretions by
anticholinergic actions.They have been specially
promoted for cough in respiratory allergic states .
• Chlorpheniramine:2-5mg
• Diphenhydramine:15-25mg
• Promethazine:15-25mg
Expectorants
These are the drugs that facilitate removal of respiratory secretions by
coughing.
Mechanism of actions
1.sedative expectorants
• They soothe inflamed respiratory mucosa by stimulating protective
mucus secretions from secretory cells of respiratory airways.
• Increase fluidity of sputum ,that helps in its expectoration by cough.
2.Stimulant expectorant
• Stimulates healing and repair of chronically inflamed respiratory
mucosa.
Cholinergic drugs
• These act on the cholinergic
receptors of the bronchi and
increases bronchial secretions.these
are not used clinically due to strong
side effects.

SIDE EFFECTS
•
•
•

Decrease heart rate
Decrease force of contraction
Decrease B.P

Sodium and potassium salts of iodine
• KI is active in increasing the volume
and decreasing the viscosity of
bronchial secretion. Being a bronchial
gland irritant as well as gastric
Irritant ,it directly and reflexly
increases the bronchial secretions.
SIDE EFFECTS
• Unpleasant taste
• Sneezing and conjuctival irritation
resembling common cold
• Skin rashes
• Goiter and hypothyroidism
• Acne

Dose: 200-300mg
Contraindications :
Asthmatic patients
MECHANISM OF ACTION
All these drugs except water
irritate the gastric mucosa
.Impulses goes to the vomiting
centre and from there
impulses are sent to
bronchioles and bronchial
secretion increases.
DOSE
Ammonium salts: 0.3-1gm

ADVERSE EFFECTS:
Nausea,vomiting
MUCOLYTIC EXPECTORANT:
BROMHEXINE

• Bromhexine is a mucolytic agent used in the treatment of respiratory
disorders associated with viscid or excessive mucus
• It reduces viscosity of bronchial secretions by depolymerization of
mucopolysaccharides in ground substances of bronchial secretions and
by liberating lysosomal enzymes resulting in thinning of the mucus.
• Derived from Adhatoda vasica
USES
1.to reduce sputum viscosity in cystic fibrosis
2.chronic asthma and bronchitis
3.productive cough
DOSE
Bromhexine:

Carbocisteine:

adult 8mg TDS
Children:4mg BD

adult -750mg TDS initially
1.5 g daily in divided doses
ADVERSE EFFECTS
Rhinorrhoea,lacrimation,skin rashes, GI irritation
PERIPHERAL ANTITUSSIVES
MECHANISM OF ACTIONS
They suppress cough reflex by decreasing the input of stimuli from
cough receptors in respiratory passages.

1.DEMULCENTS
They glutinously and soothingly coat pharynx.
2.STEAM INHALATION
steam inhalation with tincture benzoin or menthol promotes
secretion of protective mucus.
3.DRUGS WITH LOCAL ANAESTHETIC ACTIVTY
Benzonatate reduce cough by depressing pulmonary stretch
receptors.It also has a central cough suppressant effect.
USES
Demulcents :cough due to sore-throat and pharyngitis
Steam inhalation :cough due to tracheo bronchitis.
Respiratory stimulants/ analeptics
• Stimulate respiration and have resuscitative value in
coma or fainting.
• Situations in which analeptics are used :
–
–
–
–

Respiratory depression due to Hypnotic drug poisoning
Suffocation on drowning
Apnoea in premature infants
Failure to ventilate spontaneously after general anesthesia

• Drugs :
–
–
–
–

Doxapram
Prethcamide
Modafinil
Reflex stimulants : ammonia, alcohol vapours
Doxapram
• Mechanism of action
– Acts by promoting excitation of central neurons , at low dose more selective
for respiratory centre
– Increases depth of respirations (tidal volume) by stimulating respiratory
center in CNS; respiratory rate may increase slightly.
– May elevate BP by increasing cardiac output, due to stimulation of carotid
and aortic body chemoreceptors
– Respiratory depression from opiates is reversed without affecting pain relief.

• Indications:
– Reversal of respiratory depression caused by anesthesia (other than muscle
relaxants) or drug overdose;
– temporary measure for acute respiratory failure in patients with COPD who
are not undergoing mechanical ventilation.
– Low doses of doxapram have been used in the treatment of apnea of
prematurity when methylxanthines have failed.
• Adverse Reactions
– Arrhythmias; tachycardia; increased BP; tightness in chest;
chest pain; phlebitis.
– Seizures; paresthesia; increased reflexes; disorientation;
dizziness; involuntary movements.
– Mydriasis.
– Nausea; vomiting; diarrhea; desire to defecate.
– Urinary incontinence and retention; elevation of BUN.
– Hemolysis (with rapid infusion).
– Laryngospasm; bronchospasm; rebound hypoventilation; cough;
hiccoughs; dyspnea.
– Flushing; feelings of warmth; sweating
– Doxapram contains benzyl alcohol, which has been associated
with fatal “gasping syndrome” in premature infants.
Route / dosage:
• ADULTS:
• Bolus IV injection 0.5 to 1 mg/kg (single dose not
to exceed 1.5 mg/kg). Can be given as multiple IV
injections q 5 min (not to exceed total dose of 2
mg/kg).
• IV infusion Initial rate: 5 mg/min until satisfactory
respiratory response is noted. Maintenance rate:
1 to 3 mg/min. Maximum total infusion dose is 4
mg/kg

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14drugs acting on respiratory system expectorants, respiratory stimulants

  • 2. • Cough is a protective reflex that removes foreign material and secretions from the bronchi and bronchioles. • Coughing may be initiated either voluntarily or reflexively • Two types : – Productive cough( useful cough) – Unproductive cough ( useless cough)
  • 3. Classification ANTITUSSIVES/COUGH SUPPRESSANTS a. Opiods and related drugs • • • • • Codeine Hydrocodone Pholcodeine Morphine Ethylmorphine EXPECTORANTS a. Directly acting: Sodium and potassium salts of iodine , citric acid or acetic acid , guaicol, tolu balsam, terpene hydrate, Guaiphenesin b. Reflexly acting : i) Saline expectorants : NH4Cl, NaHCO3 ii) Ipecacuanha syrup b. Non-opioids • Dextromethorphan • Caramiphene • Noscapine c. Mucolytics : c. Antihistamines • Chlorcyclizine • Diphenhydramine • promethazine Pharyngeal demulcents : Lozenges, cough drops , linctuses containing syrup, glycerine , liquorice i) ii) iii) Bromhexine Acetylcysteine Carbocisteine
  • 4. Specific treatment approach of cough • Upper respiratory infection: antibiotics • Smoking / chronic bronchitis : cessation of smoking , avoidance of pollutants • Pulmonary tuberculosis : antitubercular drugs • Asthmatic cough: antiasthmatics • Postnasal drip due to sinusitis : antibiotic , nasal decongestants , H1 blockers • Gastroesophageal reflux : bed head elevation, light dinner , diet modification , drugs for PUD • ACE inhibitor associated cough: substitute by losartan, indomethacin , nifedipine
  • 5. 1 . MORPHINE • It is an effective antitussive but it produces depression of respiratory centre and drug dependence .Hence it is not used at clinical level for antitussive. 2. CODEINE PHOSPHATE • It is centrally acting cough suppressant. MECHANISM OF ACTION • Depresses cough reflex by a direct depressant effect on cough centre . USES • Used for dry and painful cough. • Standard narcotic antitussive • Severe pain • Antispasmodic • Diarrhoea ADVERSE EFFECTS • • • • • • • Nausea Vomiting Constipation Addiction Drowsiness Respiratory depression In case of liver disease ,increased dose causes convulsions in children PRECAUTIONS • Prostatic hypertrophy • Hepatic disease CONTRAINDICATIONS • In bronchial asthma because it induces bronchospasm. • Children below 2 year
  • 6. DOSE Mild to moderate pain Adult dose ::30-60mg every 4 hours ,to a maximum of 240mg daily Child dose:1-12 years:3mg/kg daily in divided doses Dry or painful cough Adult dose:15-30mg 3-4 times daily child dose:7.5-15mg 3-4 times daily
  • 7. PHOLCODINE • It is semisynthetic derivative of codeine. • It is It is available as linctus and may be given to children ..It doesnot cause constipation and less liable to cause addiction as compared to codeine. • It is more potent than codeine . MECHANISM OF ACTIONS • Same as codeine USES • For dry and painful cough. ADVERSE EFFECTS • Nausea • Drowsiness
  • 8. DEXTROMETHORPHAN • The antitussive activity of the drug is about equal to that of codeine.the drug produces no analgesia or addiction or CNS depression.And is also devoid of constipating actions. MECHANISM OF ACTION • Acts centrally to elevate the threshold for coughing. USES • Widely used anti tussive and is the constituent of many cough remedies. • Used for dry cough ADVERSE EFFECTS It occasionally causes • Drowsiness • Dizziness • Excitation • Mental confusion • GI disturbances CONTRAINDICATIONS • Liver disease DOSES • 10-20mg every 4hrs or 30mg every 6-8hrs
  • 9. NOSCAPINE • It is as effective as codeine. • It has weak bronchodilator properties and stimulates the respiration. • IT is available as linctus and effect last for 4 hrs.It has no addicting,sedative and analgesic properties. ADVERSE EFFECTS Drowsiness and nausea DOSE Adult:15-30mg CONTRAINDICATIONS asthma
  • 10. H1 antihistamines • Many H1 antihistamines have been added to antitussive/expectorant formulations .They afford relief in cough due to their sedative and anticholinergic actions but lack selectivity for the cough centre.They have no expectorant action,may even reduces secretions by anticholinergic actions.They have been specially promoted for cough in respiratory allergic states . • Chlorpheniramine:2-5mg • Diphenhydramine:15-25mg • Promethazine:15-25mg
  • 11. Expectorants These are the drugs that facilitate removal of respiratory secretions by coughing. Mechanism of actions 1.sedative expectorants • They soothe inflamed respiratory mucosa by stimulating protective mucus secretions from secretory cells of respiratory airways. • Increase fluidity of sputum ,that helps in its expectoration by cough. 2.Stimulant expectorant • Stimulates healing and repair of chronically inflamed respiratory mucosa.
  • 12. Cholinergic drugs • These act on the cholinergic receptors of the bronchi and increases bronchial secretions.these are not used clinically due to strong side effects. SIDE EFFECTS • • • Decrease heart rate Decrease force of contraction Decrease B.P Sodium and potassium salts of iodine • KI is active in increasing the volume and decreasing the viscosity of bronchial secretion. Being a bronchial gland irritant as well as gastric Irritant ,it directly and reflexly increases the bronchial secretions. SIDE EFFECTS • Unpleasant taste • Sneezing and conjuctival irritation resembling common cold • Skin rashes • Goiter and hypothyroidism • Acne Dose: 200-300mg Contraindications : Asthmatic patients
  • 13. MECHANISM OF ACTION All these drugs except water irritate the gastric mucosa .Impulses goes to the vomiting centre and from there impulses are sent to bronchioles and bronchial secretion increases. DOSE Ammonium salts: 0.3-1gm ADVERSE EFFECTS: Nausea,vomiting
  • 14. MUCOLYTIC EXPECTORANT: BROMHEXINE • Bromhexine is a mucolytic agent used in the treatment of respiratory disorders associated with viscid or excessive mucus • It reduces viscosity of bronchial secretions by depolymerization of mucopolysaccharides in ground substances of bronchial secretions and by liberating lysosomal enzymes resulting in thinning of the mucus. • Derived from Adhatoda vasica USES 1.to reduce sputum viscosity in cystic fibrosis 2.chronic asthma and bronchitis 3.productive cough DOSE Bromhexine: Carbocisteine: adult 8mg TDS Children:4mg BD adult -750mg TDS initially 1.5 g daily in divided doses ADVERSE EFFECTS Rhinorrhoea,lacrimation,skin rashes, GI irritation
  • 15. PERIPHERAL ANTITUSSIVES MECHANISM OF ACTIONS They suppress cough reflex by decreasing the input of stimuli from cough receptors in respiratory passages. 1.DEMULCENTS They glutinously and soothingly coat pharynx. 2.STEAM INHALATION steam inhalation with tincture benzoin or menthol promotes secretion of protective mucus. 3.DRUGS WITH LOCAL ANAESTHETIC ACTIVTY Benzonatate reduce cough by depressing pulmonary stretch receptors.It also has a central cough suppressant effect. USES Demulcents :cough due to sore-throat and pharyngitis Steam inhalation :cough due to tracheo bronchitis.
  • 16. Respiratory stimulants/ analeptics • Stimulate respiration and have resuscitative value in coma or fainting. • Situations in which analeptics are used : – – – – Respiratory depression due to Hypnotic drug poisoning Suffocation on drowning Apnoea in premature infants Failure to ventilate spontaneously after general anesthesia • Drugs : – – – – Doxapram Prethcamide Modafinil Reflex stimulants : ammonia, alcohol vapours
  • 17. Doxapram • Mechanism of action – Acts by promoting excitation of central neurons , at low dose more selective for respiratory centre – Increases depth of respirations (tidal volume) by stimulating respiratory center in CNS; respiratory rate may increase slightly. – May elevate BP by increasing cardiac output, due to stimulation of carotid and aortic body chemoreceptors – Respiratory depression from opiates is reversed without affecting pain relief. • Indications: – Reversal of respiratory depression caused by anesthesia (other than muscle relaxants) or drug overdose; – temporary measure for acute respiratory failure in patients with COPD who are not undergoing mechanical ventilation. – Low doses of doxapram have been used in the treatment of apnea of prematurity when methylxanthines have failed.
  • 18. • Adverse Reactions – Arrhythmias; tachycardia; increased BP; tightness in chest; chest pain; phlebitis. – Seizures; paresthesia; increased reflexes; disorientation; dizziness; involuntary movements. – Mydriasis. – Nausea; vomiting; diarrhea; desire to defecate. – Urinary incontinence and retention; elevation of BUN. – Hemolysis (with rapid infusion). – Laryngospasm; bronchospasm; rebound hypoventilation; cough; hiccoughs; dyspnea. – Flushing; feelings of warmth; sweating – Doxapram contains benzyl alcohol, which has been associated with fatal “gasping syndrome” in premature infants.
  • 19. Route / dosage: • ADULTS: • Bolus IV injection 0.5 to 1 mg/kg (single dose not to exceed 1.5 mg/kg). Can be given as multiple IV injections q 5 min (not to exceed total dose of 2 mg/kg). • IV infusion Initial rate: 5 mg/min until satisfactory respiratory response is noted. Maintenance rate: 1 to 3 mg/min. Maximum total infusion dose is 4 mg/kg