Drugs used in the Treatment of Peptic Ulcer Flashcards
GIT Control
Neuronal
Myenteric Plexus
Meissner Plexus
Receive PS fibers from N.X
Symp. fiber innervations: blood vessels, SM, some
glandular cells
Neurons within Plexus = Enteric NS
Secretion of neuropeptides: ACh, NE, purines, 5HT
Hormonal
Endocrine Secretion-> Gastrin
Paracrine Secretion-> Histamine
Cells of Stomach
Mucous Neck Cells
Secrete mucous and bicarbonate
Parietal Cells
Secrete HCl and IF for absorption of B12, Ca2
Enterochromaffin Like Cells
Secrete histamine-> stimulate HCl secretion
Chief Cells
Secrete pepsinogen and gastric lipase
D Cells
Secrete somatostatin-> inhibits HCl secretion
G Cells
Secrete gastrin -> stimulate HCl secretion
Physiology of Gastric Acid Secretion
Around 2.5l/day
Phases:
Cephalic: taste and smell
Gastric: mechanical and chemical
Intestinal
Mechanism
Neuronal control: N. X--> ACh
Paracrine control: Enterochromaffin- like and mast cells:
histamine
Endocrine control: G cells-> gastrin
Regulation
Gastric contents increase secretion
protein, peptides, AA, milk, Ca salts
Neuronal factors
Increase: N.X and intramural plexi
Decrease: ACh-> decrease pH-> decrease HCl secre.
Hormonal Factors
Epinephrine: via b R-> increase gastric acid secretion
Somatostatin: reduce gastric acid secretion
Mechanism of Gastric Acid Secretion
Transporters req.
1) Cl/HCl antiporter
Cl into cell; HCl from cell-> plasma
2) Cl/K Cotransporter
Cl and K from cell into lumen
3) K/H ATPase
H from cell into lumen (created by carbonic anhydrase)
K from lumen into cell
Pathological Conditions
Erosive and ulcerative disease of upper GIT
GERD
Acute peptic ulcer: due to drugs (NSAIDs, steroids,
alcohol)
Chronic peptic ulcer: disturbance between aggressive
factors and protective factors
Zollinger Ellison Syndrome (ZES)
Gastrin producing tumor
Therapy of Acid Related GIT Diseases
Basic Principles
Inhibition of pain
Helping ulcer heal
Prevent ulcer recurrence
Drug Categories
Inhibition of Acid Secretion
Neutralising Gastric Acid
Increasing Resistance of Mucosa
Neutralising Gastric Acid
Antacids Definition Factors on which effects depend on Categorisation Clinical use Formulations
Are weak bases
Form salts with HCl-> decrease acidity
At pH>4 pepsin activity decreases
Mucosal PG and Bicarbonate secretion increases
Effects depend on Solubility in stomach Physiological effect Chemical activity Time of presence in stomach
Categorisation
Systemic: also water soluble at alkali pH-> absorbed
from intestines; can cause metabolic alkalosis
Non Systemic: formation of non water soluble salts in
intestine-> no absorption and influence on blood pH
Clinical Use
Good effect on duodenal ulcer
Poor effect on gastric ulcer
GERD: adjuvant th
Formulation
Tablet
Solution
Gel
Neutralising Gastric Acid
Antacids: Drug Names
NaHCO3 (Na Citrate)
CaCO3
MgO, Mg(OH)2, MgCO3
Al(OH)2
Neutralising Gastric Acid
Antacids: NaHCO3
(SYSTEMIC)
Fast effect
CO2 producing : decreases pyloric spasms-> faster
gastric emptying; but abdominal discomfort
SE in high doses
Na can cause oedema and hypertension
Milk alkali syndrome: when combo with milk: headache
dizziness, vomiting, constipation, Ca stones
Drug Interactions
Increase pH and motility in GIT-> decrease absorption
of Iron, Digoxin, Oral Anticoagulants, ABs
Neutralising Gastric Acid
Antacids: CaCO3
DON’T admin long term
Ca increases gastrin secretion and directly stimulates parietal cells-> increased acid production
Combo with a lot of milk-> milk alkali syndrome
Neutralising Gastric Acid
Antacids: MgO, Mg(OH)2, MgCO3
MgO and Mg(OH)2: fast neutralising action
NaCO3: slower, not freq. used
SE
laxative (osmotic): combo with Al(OH)3
Hypermagnesia in renal dysfunction: bradycardia
Neutralising Gastric Acid
Antacids: Al(OH)3
Weak neutralising-> slow onset and weak effect
AlCl3 salt forms gel like protective layer on injured mucosa
–> Neutralising + direct protection
SE
Obstipation (combo with Mg compound antacid)
Hyperphosphatemia in renal failure (forms insoluble
phosphate salt in bowels)
Weakness
Osteomalacia
Absorbed AI--> encephalopathy
Chelates of drugs
Inhibition of Acid Secretion
Drug Groups
Competitive Antagonist H2
Muscarine R Antagonist
PPI
Other Anti Secretory Agents
Inhibition of Acid Secretion
Competitive Antagonist H2 MoA SE Pharmacokinetics Clinical Uses
MoA
Inhibits HCl secretion in stomach (parietal cells)
Reduces histamine and partially ACh induced gastrin
secretion
Decrease volume of gastric juice, H+ and pepsin
secretion
SE (minimal)
Diarrhoea, muscle pain, skin rash
Cimetidine reduces androgens–> reduces sex.
function, gynecomastia
Also is a major CYP450 inhibitor!
Pharmacokinetics
Good oral absorption
T1/2: 1-3 hrs; once a day enough as can use high dose
Renal elimination
Clinical Uses
Duodenal ulcer: healing and post healed ulcer:
preventative dose at 1/2 th dose
Gastric ulcer: healing and post healed ulcer:
preventative dose at 1/2 th dose
GERD and ZES: high dose
H. Pylori disease
Inhibition of Acid Secretion
Competitive Antagonist H2
Drug Names
Cimetidine
Ranitidine
Famotidine
Nizatidine
Inhibition of Acid Secretion
Muscarinic R Antagonist
Nonselective
Atropine and Dicyclomine
MoA
On Mast and Enterochromaffin Like Cells:
Inhibits histamine secretion (M1 block)
On Parietal cells: inhibit gastric acid secretion(M3 block)
SE
Many parasympatholytic
dry mouth, obstipation, blurred vision
Also used as
Spasmolytic (relaxation of SM)
in Inflammatory BD
Inhibition of Acid Secretion
Muscarinic R Antagonist
M1 Selective
Pirenzepine and Telezepine
MoA
Inhibition of histamine release: Mast and Enterochro.
Cells
SE
Minimal parasympatholytic
No CNS SE
Medical Use
Ulcers not responding to H2 Blockers
Prevention of ulcer relapses
Inhibition of Acid Secretion
Proton Pump Inhibitors
Omeprazole, Pantoprazole, Rabeprazole, Esomeprazole
MoA
Irreversibly inhibit H/K ATPase (covalent binding SH
group)
Pharmacokinetics:
Good oral absorption, lipid soluble
Weak base, inactivation in stomach-> need special prep
enterosolvent capsules)
SE
Nausea, rashes, headache
Danger: long term hypoacidity: sensitive to H. Pylori
Increased tendency for hip fractures in elderly: osetoclasts have similar H+ pump. Can inhibit resolving function of osteoclasts; remodelling balance disturbed-> increase in fractures
Possible increased risk of gastric cc, carcinoid tumor
Medical Uses Severe GERD Refractory ulcer Short treatment of active duodenal ulcer ZES
Inhibition of Acid Secretion
Other
Somatostatin-> Octeotride
decrease: HCl, pepsin, secretin prod, endocrine and
exocrine functions of pancreas, splanchnic blood flow
Medical Uses
Decrease ulcer and esophageal varix bleeding
Decrease portal hypertension
Decrease pancreatic secretion
Decrease tumor growth and meta. from ZES
TCA: Trimipramine
H2R antagonist effect
Prostaglandin Antagonist: Misoprostol
Deceases parietal cell histamine stim. activity
–> decrease gastric secretion
CI in pregnancy
Gastrin antagonist: Proglumide
Ca Antagonist
Increase Resistance of Gastric Mucosa
Sucralfate
MoA
Polymerises in stomach
AL component removed from sucrose part
- charged molecule binds to + part of necrotic mucosal
peptides
Also absorbs pepsin and bile
DO NOT COMBO with secretion inhibitors or antacids
SE
Absorption of Al: encephalopathy
rarely obstipation
Increase Resistance of Gastric Mucosa
Colloidal Bismuth Compound
Bi-Chelate, Bi-Subcitrate
MoA
Bi chelates with glycoproteins of necrotic mucosa->
creates barrier on ulcer surface
Decreases pepsin activity
Increases prostaglandin production
Combo with Metronidazole and Tetracycline: H. Pylori
SE
dark discolouration of tongue and teeth
encephalopathy in renal failure
Increase Resistance of Gastric Mucosa
Carbenoxolone
MoA
Increases amount and viscosity of gastic mucus
Decreases H+ diffusion from lumen to mucosa
SE
Mineralocorticoid like due to steroid structure
–> good to combo with thiazine
Increase Resistance of Gastric Mucosa
PGE
Misoprostol
Synthetic PGE1 analogue
MoA decrease acid secretion cytoprotective of gastic mucosa Increase mucus and bicarbonate secretion Increases mucosal blood flow Decreases H+ diffusion to mucosa
SE
Dose dep. diarrhoea
Abdominal cramps
CI in pregnancy (uterus contractions)
Used in NSAID treated patients
