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

b. Non-opioids• Dextromethorphan• Caramiphene• Noscapine

c. Antihistamines• Chlorcyclizine• Diphenhydramine• promethazine

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

c. Mucolytics :

iii) Bromhexine iv) Acetylcysteinev) Carbocisteine

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

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 diseaseCONTRAINDICATIONS• 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 coughAdult 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 coughADVERSE EFFECTSIt occasionally causes• Drowsiness• Dizziness• Excitation• Mental confusion• GI disturbances CONTRAINDICATIONS• Liver diseaseDOSES• 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 EFFECTSDrowsiness and nausea DOSEAdult:15-30mg CONTRAINDICATIONSasthma

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 actions1.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.

DOSEAmmonium 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: adult 8mg TDS

Children:4mg BD

 

Carbocisteine: adult -750mg TDS initially

1.5 g daily in divided doses

 ADVERSE EFFECTS

Rhinorrhoea,lacrimation,skin rashes, GI irritation

PERIPHERAL ANTITUSSIVES

MECHANISM OF ACTIONSThey 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 ACTIVTYBenzonatate reduce cough by depressing pulmonary stretch receptors.It also has

a central cough suppressant effect. USESDemulcents :cough due to sore-throat and pharyngitisSteam 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