ANTITUSSIVES

Prof. Dr. Zeliha Yazıcı

 Cough is a protective reflex that removes foreign

materials and secretions from the bronchi and
bronchioles

Cough receptors Afferent fibers

(Chemo and mechano- Cough center
receptors) (in the vagus nerve) (in medulla)
Causes of cough
Bronchitis, pneumonia, cystic fibrosis, asthma, tumor,
granuloma, blood, edema, viral infection, postnasal
drip, esophageal reflux, middle ear disease, idiopathic,
psychogenic, foreign body, pollutants.

Drugs: ACE inhibitors, beta-blockers, nebulizer

preparations

Complications
Chronic cough can be exhausting and also cause
headache, dizziness, excessive sweating, urinary
incontinence, fractured ribs especially in women.
Histamine
LTs (LTC4, LTD4, LTE4) Bronchoconstriction
HETEs Mucus secretion
PGs (PGF2a, PGD2) Afferent stimulation
TXA2 Edema
Chemotactic factors
Free oxygen radicals

Antitussive agents

 Centrally active
 Act at peripheral sites
o Reduce the sensitivity of cough receptors
o Reduce the activity in afferent nerves

1. Opioids
 reduce the sensitivity of the cough center

Codeine (Methyl morphine)

Antitussive ® m receptors + cough receptors

Analgesic ® m receptors
Antidiaretic® m receptors
Bioavailability 65%

O and N-demethylation
Codeine Morphine (10%) +
norcodeine

Codein & its metabolites are conjugated with glucuronic

acid urine

 Half-life: 2-4 hours

 Decreases mucus secretion, causes histamine
release
 Contraindications: Should be avoided in patient
with asthma and emphysema, not recommended as
an antitussive for children <2 years of age and
elderly
 Adverse reactions: Constipation, sedation,
drowsiness, dependence, hypersensitivity, dyspnea
etc.
 Pregnancy risk factor: C/D

Clinical use: Antitussive ® 10-20 mg (Codeine

phosphate 15-30 mg)
Analgesic ® 30-60 mg (iv ® not used)

Dionin (Ethylmorphine hydrochloride)

 Antitussive, analgesic, antispasmotic
 1-5% solution ® used locally as an irritant
lymphagogue in chronic catarrhal middle ear
disease, atrophic rhinitis, painful ocular disease
(chemosis, iritis, corneal ulcer, etc)

Dextromethorphan
 Antitussive ® Reduces the sensitivity of cough
receptors
 Experimental ® Sigma opioid receptors¯, glutamate
NMDA receptors¯®Anticonvulsant, neuroprotective
 Histamine liberator ® contraindicated in bronchial
asthma
 Potentiation of MAO inhibitors
 Free addictive properties, less constipation than
codeine
 Adverse reactions: Drowsiness, nausea, CNS
depression, abnormal behavioral syndrome and toxic
psychosis in high doses
 Pregnancy risk factor: C

Pholcodine (Morpholinoethylmorphine)
 Antitussive, weak analgesic
 Has no opioid-like action
 Treatment of whooping cough

Paracodine (Dihydrocodeine bitartarat)

 Antitussive, strong analgesic
 Adverse reactions: Physical and psychological
dependence

Dicodid (Hydrocodone bitartarat)

 Antitussive, analgesic
 Adverse reactions: Physical and psychological
dependence

Oxycodone (Eucodal)
 Antitussive, analgesic
 Adverse reactions: Physical and psychological
dependence

2. Other antitussives

Noscapine (Narcotin)
 Antitussive, antispasmotic
 A potent releaser of histamin ® contraindicated in
bronchial asthma
 Adverse reactions: GIS syndrome, stupor,
dizziness, transient hypotension, urticaria

Diphenhydramine
 Antitussive ® Cough center ¯, H1 block
 Adverse reactions: Sedative, depression,
anticholinergic effects
 Pregnancy risk factor: B

Chlophedianol
 Antitussive ® Central, peripheral spasmolitic, local
anesthetic
 Adverse reactions: Nausea, drowsiness,
hallucination, anticholinergic effects

Levopropoxyphene
 Antitussive ® Central, peripheral spasmolitic
 Adverse reactions: Dizziness, stupor, nausea,
vomiting, diarrhea, abnormal vision

Isoamynil
 Antitussive ® spasmolitic, bronchodilator

Clobutinol
 Antitussive ® spasmolitic, local anesthetic
 Adverse reactions: Insomnia, dizziness, stupor, GI
irritation

Carbetapentane
 Antitussive ® spasmolitic, local anesthetic
 Anticholinergic, bronchial secretion ↓

Benzonatate
 Antitussive ® spasmolitic, local anesthetic
 Adverse reactions: Sedation, headache, dizziness,
mental confusion, visual hallucination, rash,
constipation, nausea, vomiting, GI upset, nasal
congestion

Oxsolamin
 Antitussive ® spasmolitic, bronchodilator

Butiramine dihydrogene citrate, Sodium dibunat,

Pipazetate

Demulcents
 Given as syrups or lozenges and include acacia,
licorice, glycerin, honey, and wild cheery syrups
3. Drug dependent
 ACE inhibitors
 Treatment
o NSAIDs, cromolyn
o Uses of alternative drugs

EXPECTORANTS
(Mucokinetic drugs)
Directly effective (Glyceryl guaiacolate)
Indirectly effective (Ipecac, terpin, ammonium
chloride)
Directly and indirectly effective (Iodides)

Ipecac (Cephaelis ipecacuanha)

 Emetine, dehydroemetine ® irritant action in the gut,
stimulation peripheral and central mechanism ®
Bronchial secretion ↑
 Expectorant (low doses)
 Emetic (high doses)
 Contraindications: in unconscious patients, patient
with no gag reflex, following ingestion of strong
acids, bases, or volatile oils, cardiac toxicities in
young children, or in pregnancy
 Adverse reactions: cardiotoxicity, lethargy,
vomiting, diarrhea, myopathy, hipotension
 Pregnancy risk factor: C

Dover powder ® 10% Opium, 10% ipecac , 80% inert

agents ®
Antitussive, expectorant

Glycerol guaiacolate (Guaifenesin)

 Expectorant by irritating the gastric mucosa and
stimulating bronchial secretion ®respiratory fluid
volumes↑, phlegm viscosity ¯
 Adverse reactions: drowsiness, headache, rash,
nausea, vomiting, stomach pain
 Contraindications: hypersensitivity
 Positive result in 5-HİAA and VMA determination
 Pregnancy risk factor: C

Bromhexin hydrochloride
 Directly respiratory fluid volumes↑, phlegm viscosity
¯
 Mucolytic agent

Ambroxol
 Mucolytic agent
 Treatment of acute and chronic respiratory tract
disorders associated with viscid mucus

Iodides
 NaI and KI
 Expectorant and also antithyroid agent
 Adverse reactions: Irregular heart beat, confusion,
fever, rash, goiter, salivary gland swelling, GI
bleeding, diarrhea, vomiting, stomach pain,
depression, weakness, impotence
 Contraindications: pregnancy, iodine-induced
goiter, impaired renal function, hyperthyroidism,
pulmonary edema, hyperkalemia

Ammonium chloride, ammonium acetate

 Metabolic alkalosis agent, urinary acidifying agent
 Adverse reactions: Systemic acidosis, GI irritation,
nausea, vomiting, headache, coma, mental
confusion, rash, hyperventilation
 Contraindications: severe hepatic and renal
dysfunction, primary respiratory acidosis
Poligala and Scilla
 Saponin ® Gastric irritation ® Reflex bronchial
secretion

Water

MUCOLITICS
Acetylcysteine
 Mucolytic agent
 Exerts mucolytic action through its free sulfhydryl
group which opens up the disulfide bonds (-S-S-) in
the mucoproteins thus lowering mucous viscosity
 Used in abnormal or viscid mucous secretions in
acute and chronic bronchopulmonary disease,
complications of surgery and systic fibrosis,
diagnostic bronchial studies, antidote for acute
acetaminophen toxicity
 Adverse reactions: Vomiting, nausea,
bronchospasm, stomatitis, irritation, rhinorrhea,
hemoptysis, fever

Carbocysteine
 Contraindications: peptic ulcer, pregnancy

Methylcystein, Pimetine

SURFACTANTS
Natural lung surfactant
 Synthesized and deposited by Type II monocytes
 Prevent the alveoli from collapsing during expiration
by lowering surface tension between air and alveolar
surfaces
 Used prevention and treatment of respiratory
distress syndrome (RDS) in premature infants
 Prophylactic therapy: body weight <1250 g in
infants at risk for developing or with evidence of
surfactant deficiency (administer within 15 minutes of
birth)
 Rescue therapy: treatment of infants with RDS
confirmed by x-ray and requiring mechanical
ventilation (administer as soon as possible –within 8
hours of age)

Beractant (Survanta)
 Replaces deficient or ineffective endogenous lung
surfactant
 Saline suspension
 Contains phospholipids, triglycerides, free fatty
acids, protein (SP-B and SP-C)
 Side effects: Bradycardia, oxygen desaturation,
apnea, endotracheal tube blockage, hypercarbia,
hypertension, hypotension, vasoconstriction

Colfosceril palmitate (Exosurf)

 a protein-free surfactant containing colfosceril
palmitate, cetyl alcohol, and tyloxapol

Corticosteroids (betamethasone, dexamethasone)

 antenatal corticosteroid therapy, between 24-34
weeks of pregnancy, decreases the incidence and
severity of RDS by 50% with increased survival of
preterm infants by stimulating surfactant production
in the fetal lung
 Side effects: seizure, headache, vertigo, edema,
hypertension, increased sweating, petechiae,
 ecchymoses, facial erythema, reductions in brain
and cerebellum weights, early apoptosis.
 Contraindicated in severe pregnancy-induced
hypertension and systemic fungal infection.