Emetics & Antiemetics

Drugs influencing GIT motilityLocal Emetics Central Drugs influencing GIT motility Emetics & antiemetics Anticholinergic Anti-diarrhoeal agents Antihistamine Laxative and cathertics Antiemetics D2 receptor antagonist 5HT3 receptor antagonist Cannabinoids serotonin 5HT3 & NK1 Receptors 2. Chemoreceptor trigger zone (CTZ) which is outside the BBB & accessible to emetogenic stimuli in blood / CSF. Vagal & spinal afferent nerves from GIT rich in 5 HT3 receptors. CNS: psychiatric disorders. Irritation of GIT by chemotherapy. It rich in dopamine D2 receptor & opiod receptors.Emetics & Antiemetics Definition Emetics:  Drugs which induce vomiting  Therapeutic emesis is rarely required except in cases of poisoning Antiemetics:  Drugs which suppress the vomiting  If the cause of vomiting can’t be removed. stress . Vestibular system → motion sickness via CN VIII & rich in muscarinic M1 & histamine H1 receptors 3. distention.CN X & NTS Sources afferent input to vomiting center: 1. acute infectious gastroenteritis → release mucosal serotonin & activation of the receptors → stimulate vagal afferent input to vomiting center & CTZ 4. it may be desirable to attempt to prevent / suppress it by drugs to ↓ the consequences of vomiting Pathophysiology N&V Vomiting center loosely organized neuronal region & coordinates act of vomiting thru interactions w/ CN VIII. excessive intake of 4. debilitated patient – d/t ↓ BP Antiemetics Drugs 1. Ipecacuanh a . 2. food CI Poisoning by corrosives . Apomorphi ne selective action on CTZ 2. 6.gastric perforation & damage to esophagus  petroleum distillates . hernias. stuporous or delirious patients – d/t asphyxiation & aspiration pneumonia d/t lack of coughing reflex Pregnancy. advanced PU & other GI erosions – d/t ↑intra-abdominal pressure is dangerous Cardiac decompensated patient & hypertensive patient – d/t ↑ BP 5. Young children. 3. 5HT3 receptor Site of action CTZ & gut MOA Act either on Vomiting Center(VC) / on CTZ . 5. 2. poisoning by noncorrosive substances 2. Acute 1.1.chemical pneumonitis due to inhalation Comatose.locally irritates the gut & centrally acts on CTZ Emetics Indications 1. strong acids & alkalis . Types Local mustard & water warm hypertonic solution of salt salts of heavy metals 1% Cupric sulphate 1% Zinc sulphate Ipecac*** (alkaloid) syrup MOA: irritate sensory nerve endings in the pyloric half of the stomach Central 1. Anticholinergics: Hyoscine Classification Site of action Vomiting center & Drugs 4. Acute indigestion due to 3. 4.cause scarring  eg. CTZ . single dose 50 mg Dose. 24 hrs / more.25 mg BD chemically a phenothiazine but functionally an antihistamine Uses motion sickness (given 1 hr b4 journey.75 mg IM Inhibition of histamine receptor & cholinergic receptor in VC 1. D2 receptor antagonists Phenothiazines: o Chlorpromazine(Buromazine) o Prochlorperazine (Stemetil) o Perphenazine  Butyrophenone : Haloperidol  Metoclopramide  Domperidone (Motilium) Hyoscine (Scopolamine) Cyclizine & Meclizine Promethazine gut Vomiting center and gut antagonists  Ondansetron  Tropisetron  Granisetron 5. 50 mg TDS 2.65 .0. lasts for 4 .2. antihistaminic action 2. VC – anticholinergic action. Cyclizine shortest DOA.antidopaminergic / 5HT3 antagonist action CTZ CTZ CTZ & gut CTZ & gut MOA block central muscarinic receptor on VC & gut → (relaxation of GIT) PK / Dosage 0. Meclizine longest DOA. Anti-histamine:  Cinnarizine  Cyclizine  Meclizine  Diphenhydramine (Benedryl)  Dimenhydrinate (Dramamine)  Promethazine (Phenergan) 3. Cannabinoids:  Nabilone  Pronabilol  Dronabinol CTZ Anti-emetic effect 1.6 hrs) Meclizine: motion sickness & Rx vertigo d/t labryth dysfx morning sickness CI / DI . extrapyramidal dystonia: > common in children & young adults w/ high dose fatigue. menstrual disorder . extrapyramidal effects A/E 1. small bowel intubation 5. galactorrhoea (due to ↑ prolactin secretion). patients w/ delayed gastric emptying d/t postgastrectomy. IV w/ piperazine side chain are more powerful antiemetics 1. Gastro esophageal reflux disease (together with antisecretory drugs) 2. cytotoxic drowsiness. gynaecomastia.50 mg 8 hourly IM *structurally related to procainamide (lacks LA & antiarrhythmic action)  Actions 1.100 mg TDS central inhibition of dopamine receptor on CTZ (w/ ↓ non sedative dose) motion sickness & Meniere’s disease Drowsiness (common) Phenothiazine: potent antiemetic & sedative Dose .relaxation of pyloric antrum & duodenal cap MOA: 1. prokinetic action ↑ lower esophageal sphincter tone  ↑ gut peristalsis & emptying .25 . to empty stomach before emergency anaesthesia & labour 6.hypotensi on. antiemetic action 2. IM. Central: inhibits dopamine D2 r/c on CTZ 2. prevention & Rx vomiting caused by GI disorder. spasmodic torticollis (involuntary twisting of neck). motor restless.50 . diabetes gastroparesis 3.Diphenhydram ine & dimenhydrinat e Phenothiazine & chlorpromazin e Prochlorperazi ne & perphenazine Metochlopromi de Sedating properties Dose. Peripheral → All these facilitate ACh release from enteric neurons  may be d/t 5HT4 r/c agonistic action  5HT3 r/c antagonist action  D2 r/c blocking action on cholinergic enteric neurones     rapidly & completely absorbed 1st pass metabolism present Bioavailabil ity 75% T ½: 4-6 hr Dose: 10 mg 8 hourly oral. Non ulcer dyspepsia (symptomatic improvement in chronic dyspepsia) 4. occulogyric crises (involuntary upward eye movement) 2. haemorrhage Domperidone MOA 1. block α adrenoreceptor → increase motility by ↓ relaxation Ondansetron Nabilone dose – 8 mg TDS vomiting d/t stimulation of CTZ. blocks dopamine receptor in CTZ (D2) 2. ↑ tone in lower esophageal sphincter 2. intestinal obstruction 2.drugs. postop vomiting . somnolence. diarrhoea CI 1. perforation 3. activation of dopamine receptor → inhibit cholinergic smooth muscle activation → blockade of D2 receptor → oeso & gastric contraction Actions 1. radiation & uraemia 3. used when other drugs failed for cytotoxic drug induced & radiation induced vomiting . Not penetrate well into BBB (no CNS effects) 4. dizziness. Antagonise D2 in pituitary (prolactin level) 5. Relax pyloric sphincter 3. drowsiness. antagonist ondansetron plus (ondansetron) dexamethasone w/ or w/o or lorazepam (all given IV) butyrophenone most effective combination & (haloperidol. IM. short lasting Other drugs: o Cinnarazine o Cyclizine o Dimemhydrinate o Promethazine For prophylaxis. an antiemetic is best taken 1 hr before exposure to the motion Once motion sickness has started. promethazine) is preferable Pyridoxine deficiency may occur in hyperemesis gravidarum which requires IV fluids & multivitamin supplement Vertigo    Antimuscarinics & phenothiazines are generally preferable Cyclizine / prochlorperazine may be used to relieve an acute attack Betahistine (a histamine analogue) used to improve blood circulation to the inner ear in Meniere’s disease. well tolerated droperidol) Metoclopramide may be substituted for ondansetron Vomiting d/t pregnancy     Occurs at 10-11 weeks & usually resolves by 13-14 weeks of gestation By reassurance that the problem is transient & discussion of diet* Rarely. hyoscine may be administered as a dermal patch  o       Management Vomiting d/t cytotoxic drug Vomiting after general anaesthesia Metoclopramide 5HT3 receptor antagonist or (ondansetron) ↑ effective 5HT3 receptor For severe vomiting. SC or rectal routes are required Alternatively. decision is taken to take a drug → H1 receptor antagonist or phenothiazine (eg.Motion sickness  Hyoscine best for motion sickness. also cinnarazine .