CS 17 EMETICS, ANTIEMETICS & COUGH REMEDIES

CS 17EMETICS, ANTIEMETICS & COUGH REMEDIESASHA RUSSELINSTRUCTOR HBSNStimulation of vomiting centre Vomiting centre in the medulla of the brain

It is stimulated:Directly from the labyrinth of the earBy gastric irritation or distentionBy mental activityVia the Chemoreceptor trigger zone (CTZ)By stimulation of the 5-HT; serotonin receptors of the CTZAct of vomitingBefore act of vomiting

Stimulation of vomiting centre

Produces a sensation known as nausea

Associated with increased salivary and bronchial secretions

EMETICSEMETICS Drugs that provoke vomiting are called emetics Medical use: In case of poisoning

Emetics

REFLEXCENTRALEg: ipecacuanhaEg: apomorphineREFLEX EMETICS This group of drugs produce vomiting by irritating the stomach Uses:Used as a first-aid treatment for over dosageCan be used up to 1 hour after ingestion of poison and longer for some substances, when gastric emptying is delayedParticularly useful in children CENTRAL EMETICSClosely related to morphine, but has none of its analgesic effectsUsed as a powerful emetic and also produces some cerebral depressionIt stimulates dopamine receptors in the CTZFormerly used as a emetic, but because of its depressant action, it should not be used in treating over dosageAt present, its use is confined to patients with resistant Parkinsons diseaseANTIEMETICSANTIEMETICS CAUTION:- Antiemetics should not be given if the cause of vomiting is unknown as they may hinder diagnosis Substances that trigger vomiting: It is believed that (1) acetylcholine, (2) histamine, (3) dopamine and (4) 5-HT act as intermediate transmitters in the CTZ and vomiting centre Treatment to stop vomiting: By blocking action of the above mentioned substances on their receptors (prevent or diminish vomiting)

Classes of antiemetic agentsAcetylcholine (ACh) receptor antagonists

Antihistamines

Dopamine receptor antagonists

5 HT receptor antagonists

Miscellaneous antiemetics1. ACh Receptor AntagonistsAction:- Hyoscine blocks the action of Ach on the vomiting centre Uses:- Useful for short-term control of motion-sicknessRoutes:-OralTransdermal patch (applied behind the ears, 6 hrs before starting a journey)Side Effects:-DrowsinessBlurring of vision (due to paralysis of ocular accommodation)2. AntihistaminesAntihistamines commonly used as antiemetics:-CyclizinePromethazineCinnarizine

Action:- Blocks the action of histamine on its receptorsMost antihistamines are non-specific and also block ACh receptors. This makes them effective antiemetics

2. AntihistaminesUses:-Most useful are cyclicine and promethazine and also used occassionally in severe vomiting of pregnancyCinnarizine particular favor among (1) yatchman and (2) others at risk from sea sickness. (3) Also used in vomiting associated with Menieres disease

Side Effect:-Main side effect is sedation3. Dopamine AntagonistsAction:-Several phenothiazines (anti psychotics) are powerful antiemetics blocking action in dopamine receptors on the CTZ

They are non-specific in action and therefore have side effects. Eg: Used as sedativesCommonly used dopamine antagonists for antiemetic actionProchlorperazineChlorpromazineHaloperidolLevomepromazineDomperidoneMetoclopramideProchlorperazine:-Use: Suppresses opiodinduced vomitingRoutes: - Oral - IM - IV (must be well diluted before use) Note : Dont give as SC inj B. Chlorpromazine:- Similar in action to prochlorperazine

Haloperidol:-

Similar action, but longer-acting and less sedating

Levomepromazine:-

Uses: (1) Used particularly in terminal care, to control vomiting (2) Also reduces agitation

Domperidone:- Uses : (1) Suppresses vomiting that accompanies long-term treatment with the opiods, levadopa and with the mildly emetic cytotoxic drugs (2) Enhances gastric emptying

Limitation : Only about 15% of the oral dose reaches the circulation (No parenteral preparations available)

Advantages : (1) Less sedating than chlorpromazine (2) Less liable to produce dystonic reactions than metoclopramide because its action on nervous system confined to the CTZMetoclopramide:-

Uses : (1) Increases gastric emptying (2) Central action on the vomiting centre a) Fairly effective antiemetic (given orally or IM) b) Used in post-operative & opoid induced vomiting and in migraine c) Very large doses block 5-HT receptors and is used to prevent vomiting due to cytotoxic drugs

Metoclopramide:-

Adverse Effects :

(1) Dystonic reactions even with normal doses and more common with young people (2) Prolonged use can result in tardive dyskinesia4. 5-HT ANTAGONISTSDrugs : OndansetronGranisetron

Action :Block the 5-HT receptors associated with the central connections of the vagus nerve in the brain stem in close proximity to the CTZ

Uses :Prevent vomiting in patients receiving highly emetic cytotoxic drugs such as cisplatin, which release 5-HT5. MISCELLANEOUS ANTIEMETICSCannabinoids

Betahistine

Dexamethazone

BenzodiazapinesCannabinoidsDerivative of Cannabis sativa (marijuana)Cannot be prescribed at present, but nabilone a derivative is available

Uses : Used as antiemetic in controlling vomiting in patients receiving cytotoxic drugs

Side Effects : (1) sedation (2) confusion

Betahistine

Uses : Used as antiemetic and its use is confined to Menieres disease, in which vertigo and vomiting are due to a disturbance in the labyrinth of inner ear

Action : Believed to lower pressure in the inner ear and thus relieve symptoms

Dexamethazone

Useful antiemetic during cancer chemotherapy

Benzodiazapines Example :- Diazepam (valium)

Uses : (1) Used in combination with other antiemetics (2) Useful for relieving anxiety (Has no specific antiemetic effect)COUGH REMEDIESCOUGH SUPPRESSANTS(ANTI-TUSSIVE DRUGS)

Anti-tussives are avoided for patients having cough associated with chronic bronchitis, bronchiectasis and asthmaMain group of anti-tussivesDemulcents

Opioids

Antihistamines1. DEMULCENTSAction:-Irritation of mucous membrane of mouth and throat

Coughs

Soothing action (of syrup)

Forms protective film over inflamed tissues

Example : Simple linctus (flavored syrup) avoid in diabetic patients as it contains sugarOPIOIDSMain opioid groups used as anti-tussives :

Codeine

Dextromethorphan

PholcodineA. CodeineMost popular in this group is linctus codeine (BPC)

Widely used, but not very effective unless given in doses above those usually recommended leads to constipation

B. DEXTROMETHORPHANStructure related to levorphanol, a synthetic narcotic analgesic

A number of OTC medications for cough, cold and influenza contain dextromethorphan

Potent as codeine as cough suppressant and also like codeine cause constipation depending on the dosage and frequency of useC. PHOLCODINEClosely related to codeine and depress cough centre

Experiments suggest that they are more active than codeine and have similar side effects

Action lasts for 4 6 hours

Included in various mixtures, including linctus pholcodine (BPC)

In terminal care, morphine and diamorphine (heroin) required to relieve a distressing coughINHALATIONS AND MUCOLYTIC AGENTSMucolytic agents liquefy mucus

Steam good expectorant liquefies sputum and enables it to be coughed up

Others :Benzoin TincturePulmonary surfactants(a) Benzoin TinctureIt is one of the balsams (obtained from especially evergreens) that contain resins and volatile oilsA tincture is a plant extract in alcoholBenzoin tincture

Added to hot water

Gives off volatile oil (when inhaled)Exerts mildly soothing effect on bronchial mucous membrane

Frequently used in acute bronchitis

Similar action,Menthol and Eucalyptus Inhalation

Considerable outpouring from bronchial glands

Transient vasoconstriction of resp. mucous membrane

Clear air passages

Uses : (1) Clearing the chest, esp. in acute bronchitis (2) Used post-operatively to avoid chest infection

Safety Point : (1) Particular care with young and elderly patients (2) Great care while inhaling to avoid spills of hot water and prevent severe burns

Nursing Point

Avoiding dehydrationGiving hot drinksPhysiotherapyMore effective than medicines in clearing the chest(b) Pulmonary SurfactantsNatural surfactants

Allow the surfaces of pulmonary alveoli to separate

Allow lungs to expand and function immediately after birth

Premature infants

Lack of natural surfactants

Lungs do not function properly

Respiratory distress syndrome Treatment of premature infants

Mechanical ventilationInhalation via endotracheal tube of colfosceril palmitate, a synthetic surfactant