Therapy of Gastrointestinal : Peptic Ulcers, GERD, and ... · Management of GERD •...

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Therapy of Gastrointestinal : Peptic Ulcers, GERD, and Vomiting-nursing By Mohie-Aldien Elsayed

Transcript of Therapy of Gastrointestinal : Peptic Ulcers, GERD, and ... · Management of GERD •...

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Therapy of

Gastrointestinal

: Peptic Ulcers, GERD,

and Vomiting-nursing By

Mohie-Aldien Elsayed

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Learning Outcomes

33.1 Explain the three phases of gastric

secretion and what stimulates the

production of acid and pepsin in the GI

tract.

33.2 Explain the different causes of peptic

ulcer disease and GERD.

33-2

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Learning Outcomes

33.3 Explain the mechanisms of action, route

of administration, adverse effects, drug

interactions, and clinical indications of

H2-receptor antagonist, antacid, proton

pump inhibitor, and antisecretory drugs,

and give examples of each.

33.4 Explain the rationale for using

anticholinergic, antiserotonin, and

antispasmodic drugs.

33-3

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Learning Outcomes

33.5 Describe GERD, and explain the

rationale for drugs used in

gastroesophageal reflux disease.

33.6 Explain the mechanism of action of

drugs that inhibit vomiting.

33-4

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Digestion

• There are three phases of gastric acid

secretion:

– Cephalic

• Sight, smell, taste, or thought of food stimulates the

release of gastric juices

– Gastric

• Stomach distends, more release of gastric juices

– Intestinal

• Fats and acids prevent secretion of gastric juices

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Digestion

• The organs of the upper GI tract aid in

digestion and absorption of nutrients from

ingested food or supplements.

• Stomach and small intestines secrete

enzymes that help in the digestion of food.

– Contain cells responsible for acid and pepsin

secretion:

• Parietal—HCl (Histamine increases release)

• Chief—pepsinogen 33-7

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Digestion

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Digestion

• Gastric acid is secreted when stimulated by

food in the stomach, sight or smell of food,

or the mere thought of food.

• When food is present in the stomach,

additional acid is secreted.

• HCl causes the stomach contents to become

acidic.

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Digestion

• The digested food is moved to the small intestine

or duodenum, where it can be absorbed.

• The duodenum triggers gastric acid production

to halt damage to GI tissue.

• Acid is secreted between meals to reduce

bacterial growth and prevent infection.

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Digestion • The mucosal lining is lubricated with

mucus and alkaline fluid:

– Forms protective barrier

– Prevents autodigestion

• Anything that interferes with the

protective function of the mucosal

barrier may lead to ulceration.

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Acid-Peptic diseases

*Dyspepsia=Abdominal pain/discomfort centered in upper abdomen.

*Peptic ulcer=Circumscribed

mucosal lesion in upper GIT A) Duodenal ulcer: • common (80%)

• 20-50 years • <1 cm diameter

• associated with H.Pylori

• Localized pain relieved by food↦↥ weight B)Gastric

ulcer:• less common (20%) • 45-55

years •1-2.5 cm diameter • Less(

e.g stress and NSAIDs ulcers) •Less

localized pain ↥by food ↦↧ weight

*Zollinger-Ellison syndrome =Gastrinoma

*GastroEsophphageal Reflux Disease

(GERD)

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Production of Ulcers

• Peptic ulcers are open sores in the

mucosal linings of the stomach and

duodenum.

• The most common cause of peptic

ulcers is an infection caused by the

bacterium Helicobacter pylori (H.

pylori).

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Production of Ulcers • Additional causes of ulcers:

– Excess gastric acid production even when food is

not present in the stomach

– Insufficient mucus secretions

– Emotional stress, alcohol, and smoking (may

aggravate or leave patients more susceptible to

ulcers)

– Certain drugs:

• Ulcerogenic—inhibit secretion of mucus, nonsteroidal

antiinflammatory drugs (NSAIDs) and steroids

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Production of Ulcers • Symptoms:

– Nausea, loss of appetite, vomiting, and dull,

gnawing pain:

• Duodenal pain is usually relieved by food.

• Gastric pain is brought on by food.

– Chronic erosion can lead to hemorrhage,

hypotension, or shock.

– Suspect perforation/chronic erosion with

blood in stool and vomit.

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Helicobacter Pylori: Gram - ,motile(6-8 flagella),helical in

shape,adapted to be an acid tolerant neutralophile.

Outer membrane

Urea H +

(+)

transporter Inner membrane

Periplasmic space

Urea

pH 2.5

pH 6.2

Urease NH3

NH3

H H

H H

+ +

+ +

Damage the epithelium

Infection →inflammatory cytokines →increase gastrine

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H. pylori Treatment

• Two antibiotics

• Bismuth

• Proton Pump inhibitors

• Antibiotic monotherapy is not

recommended due to high incidences of

resistance developing.

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m1 blockers

(Not pass BBB)

Pirenzpine

telenzpine

(-) somatostatine

(octreotide)

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Management of Ulcers • Treatment is directed at alleviating the pain

and healing the “sore” in the mucosal

barrier.

– Therapy:

• Stop smoking, avoid caffeine and alcohol, and

reduce psychological stress.

• NSAIDs should be avoided as well.

• Patients with H. pylori will require antibiotic

therapy in addition to other treatments.

• Treatment includes proton pump inhibitors, H2-

receptor antagonists, prostaglandins, anticholinergic

drugs, and antacids.

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Management of GERD

• GERD—gastroesophageal reflux disease:

– GERD involves regurgitation of digestive

juices into the esophagus.

– Main symptoms are irritation and burning in

chest or throat.

– Heartburn occurs after meals and worsens when

lying down.

– Lifestyle changes can help with management of

GERD. 33-20

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Management of GERD

• Lifestyle changes:

– Eat smaller meals.

– Eliminate certain foods.

– Lose weight (if overweight).

– Elevate the head of the bed.

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Antisecretory Drugs

• H2-Receptor Antagonists:

– Histamine receptors are found in gastric

mucosa.

– They mediate the secretion of gastric acid.

– They differ from histamine receptors involved

in allergic response.

– H2-receptor antagonists are antihistamines.

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Antisecretory Drugs

• Proton Pump Inhibitors:

– Directly inhibit the exchange of H+ ions

– Decrease HCl production

– Approved for short-term treatment of benign

gastric ulcers, active duodenal ulcers, GERD,

or long-term therapy of hypersecretory

conditions

– Can help in treatment of H. pylori as well

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Antisecretory Drugs

• Proton Pump Inhibitors:

– Omeprazole (Prilosec)

– Esomeprazole (Nexium)

– Dexlansoprazole (Dexilant)

– Lansoprazole (Prevacid)

– Pantoprazole (Protonix)

– Rabeprazole (Aciphex)

– Adverse effects—headache, diarrhea, nausea,

and constipation 33-25

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Proton pump(Na/K ATPase )inhibitors • Prodrugs activated in acid media (canaliculi of Parietal cells):

1-Should be taken with or before food as

food ↥acid production by parietal cells.

2-Not given with other antisecretory drugs

but given with antacid in different times.

3-Given as enteric coated capsule to prevent

degradation by acid in stomach and esophagus.

•Block the final step of HCl ,More potent

than H2 blockers (> 95%).Max.response can

be accelerate by more frequent doses(BID)

• Rapidly absorbed, High PPB, Extensively

metabolized by CYTP450 in liver, metabolites Exc. In urine and feaces.

• No dose adjustment in R,H impairment

•Adverse effect:

a-nausea,abdominal pain ,constipation , flatulence and diarrhea.

b-hypergastrinemic state.

c-Enzyme inhibition (↑benzodiazepine ,warfarine , phenytoin) •

Used to promote healing of gastric and duodenal ulcers,GERD,ZES.Morning

doses more effective. Given twice/day In high doses

*members:a-longer duration e.g omeprazole (20- 40mg), Lansoprazole(30mg),

Pantoprazole(40mg),esomeprazole b-shorter duration e.g rabeprazole

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Competitive H2 blockers

•Oral(T1/2=1-3h) but high dose can be given once at bed time is more

effective(safe).

•Rapid withdrawal lead to rebound hypersecreation and recurrence.

•Contraindicated in pregnancy and lactation

•May cause allergy and tachycardia

•Cause suboptimal gastric inhibition for managing acid-peptic disease and rapid

tolerance not overcome by increase dose

Members:

A)Cimitedine (400-800 mg)

-Pass BBP (Cause confusion in elderly)

-Enzyme inhibitors&decrease HBF (↑warfarin,phenytoin,diazepem,propranolol

,Ca channel blockers)

-In female ,cause galactorrhea and infertility(increase prolactine).In male,cause

gynecomastia and decrease sperm.

B)Famotidine(40 mg/d) ,Ranitidine & nizatidine (300mg/d),

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Antisecretory Drugs

• H2-Receptor Antagonists:

– As antagonists, they block the histamine

from the receptor site.

– Less acid is produced.

– Suppression of acid secretion is less than

that with the proton pump inhibitors

because only the histamine receptor is

blocked.

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Antisecretory Drugs

• H2-Receptor Antagonists:

– Administration can be oral or parenteral.

– Peak absorption is 90 minutes for cimetidine

and 2 to 3 hours for the others.

– Antacids can delay absorption of cimetidine.

– Adverse effects include headache and

constipation.

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Antisecretory Drugs

• H2-Receptor Antagonists:

– Recommended for short-term treatment of

benign gastric and duodenal ulcers:

• 60 to 80 percent healed within 4 weeks

– Used in the treatment of hypersecretory

conditions:

• Multiple endocrine adenomas

• Systemic mastocystis

• Zollinger-Ellison syndrome

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Antisecretory Drugs

• Well tolerated

• Adverse effects: headache or constipation

• Cimetidine associated with CNS effects,

mental confusion, and disorientation, in

severely ill. Also increase blood levels of

several drugs by altering metabolism

• See Table 33-4 for other drug interactions

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Antisecretory Drugs

• Prostaglandins:

– They have specific receptors in the gastric

mucosa.

– Receptors mediate bicarbonate production in

the mucosal barrier.

– Drugs such as NSAIDs inhibit prostaglandin

synthesis.

– Only one synthetic prostaglandin is approved

for use in NSAID- and aspirin-induced ulcers.

33-32

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Antisecretory Drugs

• Prostaglandins:

– Misoprostol (Cytotec):

• Should be taken throughout NSAID therapy

in patients who are at high risk for

developing ulcers

• Abortifacient—should not be given to

women of childbearing age

• Adverse effects—diarrhea, headache,

abdominal pain, flatulence, nausea, and

constipation

33-33

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Antisecretory Drugs

• Anticholinergic and Antispasmodic

Drugs:

– Anticholinergics:

• Block muscarinic receptors, which directly

decreases gastric acid secretion and intestinal

motility

– Antispasmodics:

• Used to decrease intestinal motility

33-35

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Antisecretory Drugs • Anticholinergic and Antispasmodic Drugs:

– Adverse effects:

• CNS side effects

• Mydriasis

• Blurred vision

• Increased intraocular pressure

• Urinary retention

– Drug interactions:

• Cardiac glycosides

• Antipsychotics

• Tricyclic antidepressants

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Management of Acid-peptic disease

A)General measures: 1-Rest

2-Small frequent light meal.

3-Avoid smoking,xanthenes(coffe,tea,cola),carbonated water , chewing

gum ,NSAIDs ,corticosteroids , stomachic , obesity,

parasympathomimetics ,reserpine

B)Specific measures

1-Zollinger-Ellisson syndrome (Gastrin-secreting tumor) Higher dose of

PPIs ,H2 blockers + octreotide(also is used in acromegaly &severe diarrhea)

2-Peptic Ulcer diseases

a- Active→ Antisecretory(full dose, 2weeks) and eradicate

H.Pylori.

b-Prevent recurrence →H2 blockers and PPIs (1/2 dose,6 months)

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Antisecretory Drugs

• Gastrointestinal Stimulants:

– Induce contractions of the upper GI tract to

prevent reflux

– Keep damaging stomach contents from

reaching the esophagus

– Metoclopramide:

• Increases tissue sensitivity to acetylcholine

• Works on GI smooth muscle

33-38

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Antisecretory Drugs

• Gastrointestinal Stimulants:

– Metoclopramide

• Works best at reducing daytime, food-induced

heartburn

• Used before meals for diabetic gastroparesis

• Taken 30 minutes before meals

• For GERD, an additional dose at bedtime

• Adverse effects—restlessness, drowsiness, diarrhea,

and headache

33-39

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Antisecretory

Drugs

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Antisecretory

Drugs

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Table 33:4

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Acid Neutralization: Antacids

• MOA: neutralize gastric activity by reacting

with HCl

• IND: relieve pain and indigestion of

overeating, GERD, hiatal hernias, and

peptic ulcers

• Most antacids are nonsystemic and work

directly on the stomach.

• Use should be limited.

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Antacides

A)systemic :• Rapid onset.

• Cause: 1- alkalosis

2-Co2 release(distention,discomfort rebound hyperacidity,rupture )

e.g.NaHco3(short duration,)-Ca HC03 (long duration ,

constipation,hypercalcemia)

B) Local: •Delayed onset ,long duration

e.g.*Al(OH)3*,Al po4 gel (cause constipation)

-Mg trisilicate*,MgO,Mg OH(cause diarrhea)

*Physical antacid(adsorb HCl,pepsin&demulcent)

•Mg,AL decrease absorption of H2 blockers ,quinolone

,warfarin,digoxin

Helicobacter Pylori eradication

-Bismuth subsalicylate +metronidazole

+tetracycline+PPIs(1-2W)

-Clarithromycin+amoxacilin+PPIs(2W)

-Clarithromycin+PPIs(4W)

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Acid Neutralization: Antacids

• Adverse effects:

– Constipation

– Hypophosphatemia (aluminum compounds)

– Hypercalcemia

– Acid rebound

• Drug interactions:

– May alter the absorption and excretion of other

drugs

– Tetracyclines

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Acid Neutralization: Antacids

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Barrier Enhancers: Sucralfate

• A complex of aluminum hydroxide and

sulfated sucrose that is used to promote

healing of peptic ulcers. Similar to the

antacids, sucralfate is a nonsystemic drug

that exerts its effect locally in the GI tract.

Unlike antacids, however, sucralfate does

not alter gastric pH.

33-50

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Mucosal protective drugs(↑protective factors) A) Pg E1,2 analogue (misoprostol 200mg TDS)

- cause diarrhoea and Contraindicated in pregnancy (oxytocic) .

B) Carbenoxalone

-Aldosterone like action (salt and water retention,hypokalemia.)

Coating substances A) Sucralfate(sulphated sucrose-Al(OH)3):

-Polymerize at pH <4 forming stick gel(not used with antacid)

-decrease absorbtion of lansoprazole ,H2

blockers,quinolones,phenytoin.

-cause constipation,dry mouth

-1gm/6h(1h before meal)

B) Bismuth subsalicylate (colloid)

-Bind to mucosa and necrotic glycoprotein.

-Weak acid and H.Pylori bactercidal.

-240 mg BID ½ h before meal

-cause black color of oral cavity and faeces

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Barrier Enhancers: Sucralfate

• MOA: forms protective barrier over

damaged mucosa by binding proteins

exuded from damaged cells

• IND: short-term treatment of duodenal

ulcers

• Decreases the bioavailability of digoxin,

quinolone, quinidine, ketaconazole, and

warfarin

1-52

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Prokinetic (↥upper GIT motility↦ ®in GERD,Hiccup,diabetic gastroparesis ,P.ulcer)

1)Antiemetics (centeral,dual) 2) Cisapride (↥5HT4 ↦↥Ach release)

Antidiarrheal: 1) Adsorbant e.g Kaolin,bismuth

2)Absorbant e.g. pectin in rice,carrot,apple

3)Astringent e.g. Tincture catecho ↦ tannic acid

4)Antimotility: *m blockers ? *Volatile oil (pipperment,anise)

*Opioids(μ) e.g Loperamide(Not pass BBB ) &diphenoxylate (+atropine ↦ Imodium )

In addition to correct dehydration,acid/base &electrolyte balance

Laxatives: *Physical=faecal softener/lubricant(delayed onset,given at night)

e.g.Glycerin,Dioctyl Na sulphosuccinate,liquid parafine (↧abs.of Vit.D,K.E

contraceptives,may cause polyp,purities ani)

*↥ motility:a-Bulk(↥ plexus↦↥A.ch. inL&S intestine)*onset (1-3h)↦given at

morning) 1-Indigestible polysaccharides(cellulose=bran)

2-Osmotic e.g. • Mg SO4=Epsom’ salt =saline purgative

•Lactulose (48 h,need regular intake)↦Lactic by bacteria ↦↧pH ↦↧bacterial NH4↦

used in hep.encephalopathy with neomycin.

b-Stimulant=chemical irritant (X=colic,dehydration,Exc.in milk,pelvic congestion

(Abortion & dysmenorrhea),↧abs.of nutrients/drugs )e.g

* Mild(Castor oil ↦ glycerol+retionic acid (given at night)

*Moderate(at night)e.gAnthracin(cascra,rhubrab),bisacodyl ,phenolphaline(long dur.)

*Severe (obsolete)e.g croton oil

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Cholaguge (G.bladder evacuation):

1-M agonist 2-MgSO4 , fat/oil ↦ cholcystokinin

Choleretic(↥bile synthesis): =Bile acids *natural (cholic

A.,deoxycholic A.) *Synthetic (Na glycocholate,Na taurocholate)

Hydrochloretic:*e.g.dehydrocholic A.,salicylate

* used in flatulence,constipation,indigestion

Sialogogue=pilocarpine(# atropine)

Biliary colic treated by nitroglycerine,atropine,meperdine/morphine

Anti-Inflamatory bowel syndrome:

e.g.Chron’s(all gut),ulcerative colitis (colon) treated by:

1-sulphasalazine↦aminosalicylate + sulphapyrimidine(N,V,rash ifabsorbed)

2-Oslalazine 3-corticoids 4-Immunosupressive(azathioprine)

Hepatotoxic drugs:*Zonal=centrilobal necrosis(paracetamol,Ccl4)

*Viral hepatitis like(isoniazide,phenytoin,halothan)

*Chronic hepatitise (isoniazide,phenytoin,α methyl dopa)

*Cholestasis (methyltestosterone, estrogen, chlorpropamide,

chlorpeomazine,erythromycin)

*Fatty liver(tetracyclines,valproic acid)

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Management of Emesis

• Emesis:

– Vomiting:

• Natural defense mechanism for the body

• May signal disease or organ failure

• May be involuntary or self-induced

• Many causes including flu, pregnancy, motion

sickness, ear infections, and certain drugs

• Occurs in response to stimulus of the vomiting

center

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Management of Emesis

• Induction of vomiting is a well-orchestrated

interaction involving two control centers

(vomiting center [VC] and chemoreceptor

trigger zone [CTZ]) and at least 5

neurotransmitters such as serotonin,

acetylcholine, dopamine, histamine, and

substance P and their respective receptors

located in the control centers.

1-57

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Management of Emesis

• Vomiting:

– The VC is stimulated by the chemoreceptor

trigger zone (CTZ).

– Vomiting usually lasts only 2 to 3 days unless it

is a symptom of a disease.

– Emetics cause vomiting.

– Antiemetics stop nausea and vomiting.

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Management of Emesis

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stomach stim.(high salt, ipecacuancha

Pregnancy,circulating emetics (urea,

cytotoxics,digitalise,apomorphine

CTZ(D2,5HT3)

Emotion,pain,

bad smell/sight

↥ICP

Labyrnth Motion sickness

Meiner’s disease

inflammation

Vestibular nuclei

(m,H1) Vomiting

center(m) Pharynex stim.

(gag reflex)

Antiemetics(1/2 h.before PPt.factor as prevention is easier than stop,# unconsciousness)

I)For all causes except motion sickness: 1-Peripheral e.g. demulcent, LA.

2-Central * 5HT3 blockers e.g ondansetrone,granesetrone

*Pyrredoxine (Vit.B6) in pregnancy *glucocorticoids *phenothiazines

*buterophenon(m blocker) *canabiniod (nabilion)

2-Dual (D2blockers)

*Metoclopropamide (pass BBB ↦ sedation,EPS &↥5HT4 ↦↥Ach release)

*Domperidone (Less & α blockers)

II)For all causes(central):

*H1&m blockers(longer duration,used in sea,car sickness) e.g diphenhydramine

*m blocker(shorter duration,used for air sickness) e.g Hyocine

(+) Abd.muscle,diaph,pylorous &fundus of stomach (-) LOS

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Management of Emesis

• Emetics—Ipecac:

– Administer only for removal of substances indicated to be safe.

– Contact poison control before administration.

– Use only within the first 2 hours.

– Follow with water.

– If vomiting does not occur after two doses, take the patient to the hospital for gastric lavage.

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Management of Emesis

• Antiemetics:

– Prevent nausea and vomiting

– Inhibit vomiting reflex

– Act on CTZ or VC or both

• Serotonin (5-HT3) Antagonists:

– Indicated for treatment of chemotherapy- and

radiation therapys induced emesis

– Prevent serotonin from initiating signals to

CNS via vagal and spinal sympathetic nerves

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Management of Emesis

• Neurokinin-1 Receptor Antagonists (NK1):

– Substance P and NK1 receptors are the final

pathway that regulates vomiting.

– Blocking these receptors decreases nausea and

vomiting.

• Emetrol:

– Works directly on the stomach to delay gastric

emptying

– Safe for use during pregnancy

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Management of Emesis

• Dronabinol:

– Principal psychoactive substance in Cannabis

sativa

– Indicated for the treatment of nausea caused by

chemotherapy

– Only used after conventional antiemetics have

failed

• Adverse effects from antiemetics include

dry mouth, sedation, diarrhea, and blurred

vision. 33-64

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Manage-

ment

of

Emesis

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Management of Emesis