Therapy of Gastrointestinal : Peptic Ulcers, GERD, and ... · Management of GERD •...
Transcript of Therapy of Gastrointestinal : Peptic Ulcers, GERD, and ... · Management of GERD •...
Therapy of
Gastrointestinal
: Peptic Ulcers, GERD,
and Vomiting-nursing By
Mohie-Aldien Elsayed
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
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
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
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
1-6
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
Digestion
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.
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.
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.
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)
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).
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
33-14
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.
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
H. pylori Treatment
• Two antibiotics
• Bismuth
• Proton Pump inhibitors
• Antibiotic monotherapy is not
recommended due to high incidences of
resistance developing.
m1 blockers
(Not pass BBB)
Pirenzpine
telenzpine
(-) somatostatine
(octreotide)
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.
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
Management of GERD
• Lifestyle changes:
– Eat smaller meals.
– Eliminate certain foods.
– Lose weight (if overweight).
– Elevate the head of the bed.
33-21
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.
33-22
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
33-24
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
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
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),
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.
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.
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
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
1-31
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
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
1-34
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
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
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)
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
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
Antisecretory
Drugs
Antisecretory
Drugs
Table 33:4
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.
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)
Acid Neutralization: Antacids
• Adverse effects:
– Constipation
– Hypophosphatemia (aluminum compounds)
– Hypercalcemia
– Acid rebound
• Drug interactions:
– May alter the absorption and excretion of other
drugs
– Tetracyclines
Acid Neutralization: Antacids
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
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
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
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
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)
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
33-56
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
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.
33-58
Management of Emesis
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
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.
33-61
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
33-62
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
33-63
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
Manage-
ment
of
Emesis
Management of Emesis