PHARMACOTHERAPY OF COUGH

WHAT IS COUGH?
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes Although a beneficial reflex , if repeated and persistent,exhausts the patient, disturbs sleep, and become a social nuisance.

Comprise of three steps:
STEP 1

COUGH REFLEX
• AN INSPIRATION

• BUILDING UP OF PRESSURE IN THE LUNGS BY CONTRACTIONS OF EXPIRATORY MUSCLES AGAINST A STEP 2 CLOSED GLOTTIS • FORCEFUL EXPIRATION THROUGH NARROWED AIRWAYS WITH HIGH VELOCITY OF AIRFLOW,WHICH STEP 3 SWEEPS IRRITANT UP TOWARD PHARYNX

CAUSES OF COUGH

1. Respiratory tract infection: cold, flu, pneumonia, bronchitis, sinusitis 2. Postnasal drip (from allergies or a cold) 3. Certain medications called ACE inhibitors used to treat high blood pressure and heart disease: (Captopril (Capoten) 4. Allergies 5. Asthma 6. Chronic obstructive pulmonary disease (COPD), which is from either emphysema or chronic bronchitis or both 7. Aspiration (foreign matter drawn into the lungs) 8. Congestive heart failure 9. Gastroesophageal reflux disease, where stomach acid backs up into the esophagus 10. Cigarette smoking or exposure to secondhand smoke

DRUG CLASSIFICATION .

terpene hydrate) • 2.EXPECTORANTS: DRUGS FOR PRODUCTIVE COUGH ALKALINE EXPECTORANTS(pottasium citrate and acetate) NAUSEANT EXPECTORANTs(tincture ipecacuanha . carbocyateine) .MUCOLYTICS(acetylcysteine . bromhexine . ammonium chloride and carbonate) SALINE EXPECTORANTS(sodium and potassium iodide SEDATIVE EXPECTORANTS STIMULANT EXPECTORANTS(creosate.1.

STEAM INHALATION(with methanol) C.DRUGS WITH LOCAL ANESTHETICS ACTIVITY(benzonatate) 2. herion) B.PERIPHERAL ANTITUSSIVES: DRUGS FOR UNPRODUCTIVE COUGH A.CENTRAL ANTITUSSIVES A. Non-addicting(codeine . II.lemon juice) B.OPOIDS ANTITUSSIVES I. pholcodeine) Addicting drugs(morphione . methadone .NONOPIOIDS ANTITUSSIVES(dextromethorphan ) .DEMULCENTS(honey.1.

PHARMACOTHERAPY OF COUGH COUGH SUPPRESANTS EXPECTORANTS MUCOLYTICS .

COUGH SUPPRESSANTS Inhibit irritant and unproductive cough reflex Are of two types: CENTRALLY ACTING: PERIPHERALLY ACTING: Local anesthetics Benzoate Demulcents OPOIDS-codeine and pholcodeine NONOPOIDS-noscapine . dextromethorphan .

CENTRALLY ACTING COUGH SUPPRESSANTS OPIOIDS NONOPIOIDS CODEINE PHOLCODEINE NOSCAPINE DEXTROMETHORPHAN .

however. The precise mechanism of action of codeine is not known. OPIOIDE AS COUGH SUPRESEANTS CODEINE: Codeine is a weak narcotic pain-reliever and cough suppressant similar to morphine and hydrocodone. a small amount of codeine is converted to morphine in the body. In fact. codeine binds to receptors in the brain (opioid receptors) .They act centrally on the cough center in the brain to suppress dry hacking cough. like morphine.

[9][10] A portion (~ 15%) of the codeine is N-demethylized to norcodeine Codeine is metabolized to C6G by uridine diphosphate glucuronosyl transferase UGT2B7. .CONTD. Only 5% of the dose is O-demethylated to morphine. only about 5% of codeine is metabolized by cytochrome P450 to morphine. Codeine was considered a prodrug.since it is metabolised in vivo to the primary active compounds morphine . which is the metabolite that is most responsible for codeine's analgesia. But now 80% of codeine is conjugated withglucuronic acid to Codeine-6glucuronide(C6G). which in turn is immediately glucuronidated at the and excreted renally.

abdominal pain.SIDE EFFECTS OF CODEINE The most frequent side effects of codeine include lightheadedness. Other side effects include allergic reactions. rash and itching. . constipation. dizziness nausea. Mental and physical dependence can occur but are unlikely when used for short-term cough treatment. vomiting shortness of breath. Codeine is habit forming. and sedation.

. it has no opioid-like actions.PHOLCODINEPholcodine is a drug which is an opioid cough suppressant (antitussive) Although structurally related to codeine.

partly by a direct effect on the cough centre in the medulla .MECHANISM OF ACTION: Pholcodine is readily absorbed from the gastrointestinal tract and freely crosses the blood-brain barrier. It acts primarily on the CNS causing depression of the cough reflex.

.Pharmakokinetics Pholcodine is slowly biotransformed in the body via oxidation and conjugation to a series of metabolites that are eliminated primarily in the urine. Its use is therefore contraindicated in patients with liver disease. average half-life ~ 2-3 days metabolized in the liver and its action may be prolonged in individuals with hepatic insufficiency (i. liver problems).e.

SIDE EFFECTS OF PHOLCODEINE RARE and may include dizziness and gastrointestinal disturbances such as nausea or vomiting Adverse effects such as Constipation drowsiness. ataxia and respiratory depression have been reported occasionally or after large doses. . excitation.

NON-OPIOIDS AS COUGH SUPRRESSANTS .

noscapine’s anti-cancer effect has been demonstratedwhen taken at doses higher than those used for cough suppression . Noscapine is a very safe cough suppressant (antitussive)which has been in use for many decades In recent years.NOSCAPINE NOSCAPINE is naturally occuring nonaddictive opium alkaloid.1.

and rectally in suppositories. Noscapine can be given orally in tablets. and syrup.FATE OF NOSCAPINE MODE OF ADMINISTERATION: The common form of noscapine which is used in cough suppression is noscapine hydrochloride (Hcl) Noscapine Hcl has a half-life of 4. . lozenges.5 hours in the body SIDE EFFECTS: High doses may cause vomiting nd abdominal discomfort. capsules.

for the temporary relief of cough caused by minor throat and bronchial irritation (such as commonly accompanies the flu and common cold.DEXTROMETHORPHAN The primary use of dextromethorphan is as a cough suppressant. as well as those resulting from inhaled irritants.2. .

without inhibiting ciliary activity .MECHANISM OF ACTION At therapeutic doses. It elevates the threshold for coughing. dextromethorphan acts centrally (brain) as opposed to locally (on the respiratory tract).

where it enters the bloodstream and crosses the blood-brain barrier.Following oral administration. The first-pass through the hepatic portal vein results in some of the drug's being metabolized by O-demethylation into an active metabolite of dextromethorphan called dextrorphan. dextromethorphan is rapidly absorbed from the gastrointestinal tract. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite PHARMOCOKINETICS .

SIDE EFFECTS OF DEXTROMETHORPHAN 1. 5. dizziness lightheadedness drowsiness nervousness restlessness nausea vomiting stomach pain . 4. 7. 2. 8. 6. 3.

PERIPHERRALY ACTING COUGH SUPPRESSANTS .

PERIPHERAALY ACTING COUGH SUPRRESSANTS LOCAL ANESTHETICS BENZONATATE DEMULCANTS .

LOCAL ANESTHETICS MECHANISM OF ACTION: Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane.A local anesthetic is a drug that causes reversible local anesthesia and a loss of nociception. When the influx of sodium is interrupted. . an action potential cannot arise and signal conduction is inhibited. in particular the so-called voltage-gated sodium channels. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel.

endoscopy etc which irritate pharyngeal wall and lead to cough. Local anesthetics are specially useful for short duration interventions like brochoscopy . . Lignocaine or bupivacaine can be delivered by nebulizer for anesthetizing effect in respiratory passage. 2.LOCAL ANESTHETICS IN COUGH 1.

BENZONATATE Benzonatate is chemically related to other ester local anesthetics such as procaine MECHANISM OF ACTION Benzonatate is thought to act as a local anesthetic. . thereby reducing the drive to cough after taking a deep breath. decreasing the sensitivity of stretch receptors in the lower airway and lung.

benzonatate is employed to reduce coughing in various respiratory conditions such as. emphysema. and pneumonia. It should never be used to suppress a productive cough or in place of treatment of the actual cause of cough. bronchitis. influenza. .USES OF BENZONATATE An antitussive. such as asthma treatment.

Pregnancy Lactation Children Category C Undetermined. . Safety in children younger than 10 yr of age is not established.FATE OF BENZONATATE The drug will normally have an effect within 15 to 20 minutes of taking it. The effects will last for just about 3 to 8 hours Benzonatate is not to be confused with narcotics like codeine which is also used for cough suppression.

Rash or hives Itching Difficulty breathing or swallowing Confusion . Hallucination: seeing and hearing things that aren’t really there.SIDE EFFECTS OF BENZONATATE Stuffed nose Burning in the eyes Upset stomach Dizziness Constipation Drowsiness Headache Some side effects are possibly detrimental to your health. If you experience any of these rare yet serious symptoms contact your doctor immediately.

A demulcent is an agent that forms a soothing film over a mucous membrane. Demulcents such as pectin. honey and syrup are common ingredients in cough mixtures. relieving minor pain and inflammation of the membrane. Demulcents are sometimes referred to as Mucoprotective agents. Eucalyptus oil. glycerin. DEMULCENTS . They also serve as household remedy. Eg. Lemon oil. They are useful in preventing the cough arising from dry pharynx.

Forming a soothing film on the dry mucous membrane thus protect from irritant actions of air or other irritants 2.MECHANISM OF ACTION of DEMULCENTS 1. Increase salivation in respiratory tract 3. Reduce afferent impulses arising from the irritated mucosa .

EXPECTORANTS .

and trachea Expectorants increase the bulk of the sputum by sensitizing the cells of the bronchial cavity and stimulates the bronchial reflux for the expulsion of the sputum. bronchi. . It helps in softening of the sputum making it less tenacious and hard and acting like a mucolytic agent.WHAT ARE EXPECTORANTS? A medication that helps bring up mucus and other material from the lungs.

TYPES OF EXPECTORANTS 1.INDIRECTLY ACTING .DIRECTLY ACTING 2.

Since these drugs stimulate secretion. They act by producing demulcent effect which decreases irritation and also by decreasing the viscosity of the mucus. DIRECTLY ACTING EXPECTORANTS . more fluid gets produced in respiratory tract and sputum is diluted.These bring about a stimulation of the secretory cells of the respiratory tract directly. thereby helping in easy removal of sputum.

INDIRECTLY ACTING EXPECTORANTS Act indirectly to relieve cough by irritating gastric mucosa which causes vomiting which increases respiratory tract fluid secretion thus decreasing viscosity of sputum. EXAMPLE:ammonium chloride . ipecacuanha .

MUCOLYTICS .

the glycoproteins in the mucus are linked by disulphide bonds to form polymers making it slimy. .WHAT ARE MUCOLYTICS? Normally the respiratory mucus is watery. Mucolytics liquefy the sputum making it less viscid so that it can be easily expectorated. the glycoproteins form larger polymers with plasma proteins present in the exudate and the secretions become thick and viscid. In respiratory diseases.

VARIOUS MUCOLYTICS BROMHEXINE ACETYLCYSTEINE CARBOCYSTEINE AMBROXOL .

BROMHEXINE Bromhexine is a mucolytic agent used in the treatment of respiratory disorders (eg. cough with phlegm) associated with viscid or excessive mucus. .

which is easier to expectorate.Bromhexine supports the body's own natural mechanisms for clearing mucus from the respiratory tract: Bromhexine disrupts the structure of acid mucopolysaccharide fibres in mucoid sputum and produces a less viscous mucus. It promotes the function of cilia lining the airways thus promoting the promoting the transport of mucus outside the lungs MECHANISM OF ACTION OF BROMHEXINE .

SIDE EFFECTS OF BROMHEXINE Gastrointestinal side effects may occur occasionally with bromhexine and a transient rise in serum aminotransferase values has been reported. vertigo (dizziness). . sweating and allergic reactions. Other reported adverse effects include headache.

Surfactants acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall. in improving its transport and in providing protection against infection and irritating agents.AMBROXOL It is metabolite of bromhexine and has similar uses and actions In addition to mucolytic effects It stimulates synthesis and release of surfactant by type II pneumocytes. ..

ACETYLCYSTEINE Acetylcysteine is a mucolytic agent given by mouth or inhalation of a nebulized solution in the treatment of respiratory disorders associated with the production of excessive or viscous mucus .

MECHANISM OF ACTION The mechanism of action behind the mucolytic properties of acetylcysteine appears to reside in the free sulfhydryl group of its molecular formula. The effect of this activity is a reduction in the viscosity of mucous secretions. making them less resistant to normal flow and discharge . it is believed that this group disrupts the disulfide chains typically found in mucus.

vomiting Rhinorhhea Headache Tinnitus Urticaria Chills and fever .ADVERSE EFFECT OF ACETYLCYSTEINE These include Nausea .

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