Pharmacotherapy of Cough

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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

1.EXPECTORANTS:

DRUGS FOR PRODUCTIVE COUGHALKALINE EXPECTORANTS(pottasium citrate and acetate) NAUSEANT EXPECTORANTs(tincture ipecacuanha , ammonium chloride and carbonate) SALINE EXPECTORANTS(sodium and potassium iodide

SEDATIVE EXPECTORANTS

STIMULANT EXPECTORANTS(creosate, terpene hydrate)

2.MUCOLYTICS(acetylcysteine , bromhexine , carbocyateine)

1.PERIPHERAL ANTITUSSIVES:

DRUGS FOR UNPRODUCTIVE COUGH

A.DEMULCENTS(honey,lemon juice) B.STEAM INHALATION(with methanol) C.DRUGS WITH LOCAL ANESTHETICS ACTIVITY(benzonatate)

2.CENTRAL ANTITUSSIVESA.OPOIDS ANTITUSSIVESI. II. Non-addicting(codeine , pholcodeine) Addicting drugs(morphione , methadone , herion)

B.NONOPIOIDS ANTITUSSIVES(dextromethorphan )

PHARMACOTHERAPY OF COUGHCOUGH SUPPRESANTS EXPECTORANTS MUCOLYTICS

COUGH SUPPRESSANTSInhibit 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 SUPPRESSANTSOPIOIDS NONOPIOIDS

CODEINE

PHOLCODEINE

NOSCAPINE

DEXTROMETHORPHAN

They act centrally on the cough center in the brain to suppress dry hacking cough.

OPIOIDE AS COUGH SUPRESEANTS

CODEINE:Codeine is a weak narcotic pain-reliever and cough suppressant similar to morphine and hydrocodone. In fact, a small amount of codeine is converted to morphine in the body. The precise mechanism of action of codeine is not known; however, like morphine, codeine binds to receptors in the brain (opioid receptors)

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

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

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

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, partly by a direct effect on the cough centre in the medulla

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

SIDE EFFECTS OF PHOLCODEINERARE and may includedizziness and gastrointestinal disturbances such as nausea or vomiting

Adverse effects such asConstipation drowsiness, excitation, ataxia and respiratory depression have been reported occasionally or after large doses.

NON-OPIOIDS AS COUGH SUPRRESSANTS

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

FATE OF NOSCAPINEMODE OF ADMINISTERATION: The common form of noscapine which is used in cough suppression is noscapine hydrochloride (Hcl) Noscapine Hcl has a half-life of 4.5 hours in the body SIDE EFFECTS:High doses may cause vomiting nd abdominal discomfort.

Noscapine can be given orally in tablets, lozenges, capsules, and syrup, and rectally in suppositories.

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

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

Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. 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. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite

PHARMOCOKINETICS

SIDE EFFECTS OF DEXTROMETHORPHAN1. 2. 3. 4. 5. 6. 7. 8. dizziness lightheadedness drowsiness nervousness restlessness nausea vomiting stomach pain

PERIPHERRALY ACTING COUGH SUPPRESSANTS

PERIPHERAALY ACTING COUGH SUPRRESSANTSLOCAL ANESTHETICS BENZONATATE DEMULCANTS

A local anesthetic is a drug that causes reversible local anesthesia and a loss of nociception.

LOCAL ANESTHETICS

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

LOCAL ANESTHETICS IN COUGH1. Local anesthetics are specially useful for short duration interventions like brochoscopy , endoscopy etc which irritate pharyngeal wall and lead to cough. 2. Lignocaine or bupivacaine can be delivered by nebulizer for anesthetizing effect in respiratory passage.

BENZONATATEBenzonatate is chemically related to other ester local anesthetics such as procaine

MECHANISM OF ACTIONBenzonatate is thought to act as a local anesthetic, decreasing the sensitivity of stretch receptors in the lower airway and lung, thereby reducing the drive to cough after taking a deep breath.

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

FATE OF BENZONATATEThe 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. Pregnancy Lactation ChildrenCategory C Undetermined. Safety in children younger than 10 yr of age is not established.

SIDE EFFECTS OF BENZONATATEStuffed 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.

Hallucination: seeing and hearing things that arent really there. Rash or hives Itching Difficulty breathing or swallowing Confusion

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

DEMULCENTS

MECHANISM OF ACTION of DEMULCENTS1. Forming a soothing film on the dry mucous membrane thus protect from irritant action