tbl 2 Stomach (Basic Science)

Question 1

Regions of the stomach

Orad Region: Opens to receive contents from the esophagus. It is thin walled.
- _______, _____ and part of body (corpus)

Caudad Region: This is where food is mixed and propelled into the small intestine. It is thick walled to handle the stronger contractions to help with peristalsis and trituration.
- part of body, _____, pylorus

Answer 1

cardia, fundus;

antrum

Question 2

Sphincter:

1) ________ sphincter / lower esophageal sphincter (proximal end),
2) Pyloric sphincter (distal end).

Answer 2

Cardiac

Question 3

Functions of stomach

1. Reservoir that is able to relax to accommodate large volumes of food with only small increases in pressure.
2. Grinds food to optimum-sized particles.
3. Mixes the food bolus with gastric juice and converts the bolus into ______.
4. Controls its own emptying, retaining the solid portion of the meal until most of the liquid has emptied.
5. ______ the food, retaining large particles, permitting more time for its breakdown.
6. Regulates the rate at which chyme is delivered to the intestine.
7. Secretes ____________, which kills bacteria that enters with food.
8. Secretes _______, which begins the digestion of proteins.
9. The acid lowers the pH of the gastric lumen and allows the optimal activation of pepsin. The lower pH of the gastric lumen also releases _______ from insoluble ferric salts in food.
10. Secretes intrinsic factor required for vitamin B12 absorption.

Answer 3

chyme; Sieves

hydrochloric acid; pepsin; ferric

Question 4

What are the layers of the stomach (hint: Elvis Lives Making Sweet Soulful Original Country Music Love Songs.)

Answer 4

1. Epithelium
2. Lamina Propria
3. Muscularis Mucosae
4. Submucosa
5. Submucosa plexus (Meissner’s plexus)
6. Oblique muscle
7. Circular Muscle
8. Myenteric plexus
9. Longituinal Muscle
10. Serosa

Question 5

Glands: The gastric mucosa contains several gastric glands, several of which open into a _______ on the surface of the gastric mucosa. In the pyloric and cardiac regions of the stomach, the gastric glands only secrete mucous. In the fundus and the body of the stomach, the gastric glands contain a variety of cells with different functions (see figure B). These secretions mix with mucus in the neck of the glands
and are then emptied into the stomach lumen.
1. Parietal cells (______ cells) – secrete HCl and Intrinsic factor (needed for vitamin B12 absorption)
2. Chief cells (_________ cells) – secrete pepsinogens, which are activated to the enzyme pepsin to digest proteins to peptides
3. G cells – secrete the hormone _____ (antrum)
4. D cells – secrete the hormone _____ (antrum)
5. Enterochromaffin-like cells (ECL cells) – secrete ______. They lie near parietal cells in gastric glands.
6. ______: secrete mucous

Answer 5

gastric pit;

Oxyntic; Zymogen

gastrin; somatostatin; histamine; Neck cells

Question 6

Motor functions of fed stomach are

1. Receptive relaxation of the _____ region
2. Contraction of the stomach which includes peristalsis, _______and________.
3. Gastric emptying moves contents into _______

Answer 6

orad; trituration; retropulsion; duodenum

Question 7

Receptive relaxation of the orad region of the stomach

1. Receptive Relaxation (Accommodation Reflex): Distension of lower esophagus by food relaxes the LES, and simultaneously relaxes the orad stomach.
   - No action potentials and NO phasic contractions occur.
   - The orad stomach in its relaxed state can accommodate 1.5L of food.
2. ___________: Both afferent and efferent limbs of the reflex are carried by the Vagus nerve. Vagotomy (cutting the Vagus nerve) abolishes receptive relaxation.
3. Tonic contraction: Orad stomach generally under tonic contraction regulated by _______ changes in resting membrane potential. Tonic contractions maintain a constant level of contraction or tone without regular periods of relaxation. Action potentials are not recorded from proximal smooth muscle in the stomach. There are no ___________, unlike in the caudad stomach.

Answer 7

Vago-Vagal reflex; slow; phasic contractions

Question 8

Contractions of the stomach
1. Peristaltic contractions: Peristalsis is a reflex response that is initiated when the gut wall is stretched by the contents of the lumen, and it occurs in all parts of the GI tract from the esophagus to the rectum. The stretch initiates a _______ contraction behind the stimulus and an area of relaxation in front of it. The waves of contraction move from orad to caudad direction. Waves begin in _________ and move distally along caudad stomach.
- In the receiving segment, the longitudinal
muscles ahead of the intraluminal contents _______ and the circular muscles _______ causing the lumen to expand and receive the intraluminal contents.
- Circular smooth muscles in the propulsive segment behind the intraluminal contents contract and
the longitudinal muscles relax, pushing the bolus forward. It is independent of the extrinsic innervation.

2. _________ is the process for reducing the particle size of food by grinding. To enter the duodenum, solids must be reduced to particles of 1 mm3 or less. Muscle contractions break the food into smaller pieces and mix it with gastric secretions to begin the digestive process. The strength of contractions increases as the food bolus approaches the pylorus.
3. Retropulsion: As the peristaltic wave approaches the pylorus, the pyloric sphincter closes, thus allowing only a small amount of ____________ to squirt through the sphincter into the duodenum. The more solid chyme is propelled back into the stomach for further mixing and further reduction of particle size to <1 mm3. Finally, when all the chyme is of the right size, it is propelled through the pyloric sphincter into the duodenum

Answer 8

circular; middle of stomach; contract; relax

Trituration;

liquefied chyme

Question 9

Phasic contractions in the caudad stomach: These periodic contractions followed by relaxations are found in the caudad stomach and are involved in mixing and propulsion.

Neurohormonal control of contractions

1. Parasympathetic stimulation (Vagus nerve), gastrin (hormone released by G cells in the _____) and motilin (a peptide released by M cells in the intestine and by ________________) increase action potentials and force of contractions.
2. Sympathetic stimulation, secretin (hormone released by S cells in the small intestine) and ___________________(peptide released by K cells in the small intestine) decrease action potentials and force of contractions.

Answer 9

antrum; peptidergic nerve endings; Gastric Inhibitory Polypeptide

Question 10

Gastric emptying: Stomach effects

1. Duration: ≈ 2-4 hours.
2. Size: Solids <1 mm3 enter duodenum.
3. Liquids (<20 min) empty faster than solids (<120 min).
4. Isotonic solutions empty faster than hypo-/hypertonic solutions.
5. _________ meals empty faster than protein-rich meals, which empty faster than ________ meals.
6. High caloric meals empty slowly to keep rate of delivery of caloric input to the small intestine within a narrow range.
7. Increased intragastric volume speeds up gastric emptying by triggering _________ in the stomach.
8. _______ speeds up gastric emptying by increasing force of contraction.
9. Pyloric sphincter relaxation is mediated by the Vagus nerve; vagotomy decreases relaxation of the sphincter and slows gastric emptying of solids.
10. _____________: This is a narrowing (stenosis) of the outlet of the stomach so that food cannot pass easily from it into the duodenum.

Answer 10

Carbohydrate; fatty;

mechanoreceptors;

Gastrin;

Pyloric stenosis

Question 11

Gastroparesis : Defective gastric emptying without ________________of the stomach or the duodenum can occur as a primary event, due to inherited or acquired disorders of the gastric pacemaker, or it can be secondary to disorders of autonomic nerves (particularly diabetic neuropathy) or the gastroduodenal musculature (e.g. systemic sclerosis & amyloidosis). _________ treat gastroparesis.

Answer 11

mechanical obstruction; Prokinetic agents

Question 12

Fat in the duodenum: Fat digestion triggers the production of CCK, PYY, VIP, GIP that reduce gastric motility and thereby decrease gastric emptying. Since fats are particularly effective in inhibiting gastric emptying, some people eat cheese with crackers, or snack on bread with olive oil before a cocktail party. The fat keeps the alcohol in the stomach where its absorption is slower than in the small intestine; the intoxicant enters the blood stream slowly.

• PYY, a 36-amino acid protein released by _________ in the intestinal mucosa, slows gastric motility.
• Cholecystokinin (CCK), a hormone released by ______ in the intestinal mucosa and by colonic nerve endings in response to products of digestion, increases _____________ (preventing reflux of duodenal contents into the stomach) and slows gastric emptying.
• Gastric Inhibitory Polypeptide released by K cells of the ______________ inhibits gastric secretion and motility.
• _______________________ released by peptidergic fibers of the vagus nerve decreases gastric motility.

Answer 12

L cells;

I cells; pyloric sphincter tone; duodenum and jejunum;

Vasoactive intestinal peptide (VIP)

Question 13

Acidity of the duodenum slows gastric emptying
• __________ released from S cells in the small intestine in response to acid entry into the duodenum causes contraction of the pyloric sphincter and reduces gastric emptying.
• H+ receptors in the _______________ detect low pH (pH 3-4) due to acid entry and relay this information to gastric smooth muscle via interneurons in the ____________________. Upon stimulation of the local enterogastric reflex, the release of ______ is suppressed. This reduction delays gastric emptying because Gastrin normally increases phasic contractions in the stomach, and decreased gastrin means fewer action potentials and weaker contractions.
• Why the delay? By slowing down gastric emptying, the gastric contents are delivered slowly to the duodenum, permitting time for neutralization of H+ by ______________, as is necessary for optimal function of pancreatic enzymes.

Answer 13

Secretin; duodenal mucosa; myenteric (Auerbach) plexus; gastrin; pancreatic HCO3-

Question 14

During _____________ (between meals), clearance of residual food is achieved by Migrating Motor Complexes (MMCs) that spread from the stomach or duodenum to the ileum. MMCs immediately stop with ingestion of food, but not if food is given parenterally. MMCs are not seen in the digestive period. MMCs occur in three phases, each cycle lasting 90 min.
• Phase I lasts about ____ there are no contractions or spike potentials on the underlying Basic Electric Rhythm (BER).
• Phase II lasts around 6 min and is associated with ____________ on the BER and irregular contractions.
• Phase III lasts around 3 min and is associated with regular spikes on the BER and regular contractions. It is associated with a rise in plasma motilin. Motilin, a 22 amino acid protein released by ________ in the intestinal mucosa, acts on motilin receptors on smooth muscle and on enteric nerves and increases MMCs.

Answer 14

inter-digestive periods; 80min; irregular spikes; M cells

Question 15

Secretions during MMCs: During ____________________, there is an increase in the secretion of _________, bile and pancreatic juices that clear the stomach and small intestine of luminal contents in preparation for the next meal. MMCs are possibly responsible for __________________.

__________ terminate the MMC. Vagal inputs also regulate the MMC.

Answer 15

phase II and phase III; “hunger contractions”

Gastrin and CCK

Question 16

Basal electric rhythm
• The BER are ____________ (also called pace-setter potentials) due to oscillating depolarizations and repolarizations.
• _________ or Pacemaker cells are star-shaped mesenchymal cells that lie near the myenteric plexus (between the circular and longitudinal muscle layers) and make electrical synapses with smooth muscle. They determine the frequency of BER.

Answer 16

gastric slow waves; Interstitial cells of Cajal

Question 17

HCl

• Cell: Parietal cell
• site: Body
• Function: initiates _____ digestion, frees _______ from food, frees vitamin B12 from food, kills bacteria

Answer 17

protein; ferric

Question 18

Intrinsic factor

• cell: parietal cell
• site: body
• function: required for absorption of B12 in _______

Answer 18

ileum

Question 19

Pepsinogen

• cell: chief cell, ___ cell
• sites: body, _____
• Precursor of pepsin that initiates protein digestion

Answer 19

mucus;

antrum

Question 20

Gastrin

• cell: G cell
• site: ____
• induces histamine and HCl secretion
• increases gastric motility
• _____ to gastric mucosa

Answer 20

antrum; trophic

Question 21

Somatostatin

• cell: ____
• site: ____
• inhibits gastric secretion from G cell

Answer 21

D cell; antrum

Question 22

Histamine

• cell: ______
• site: body

Answer 22

ECL cell

Question 23

Mucus, HCO3- :

• cell: mucous cells, ____ cell
• site: antrum, ___, pylorus
• protects stomach mucosa from damage

Answer 23

neck; cardia

Question 24

Enterochromaffin-like (ECL) cells are found near parietal cells in gastric glands. They are activated by the hormone gastrin (which binds to gastrin receptors on ECL cells) and by acetylcholine released from vagal fibers (which binds to _________ on ECL cells). This activation induces the release of histamine. ____________ suppresses histamine release.

Answer 24

muscarinic M3 receptors; Prostaglandin E2 (PGE2)

Question 25

Parietal cells are responsible for secreting hydrochloric acid (HCl) into the stomach lumen. The__________ (proton pump) is a key player in acid secretion. In unstimulated parietal cells, inactive H+-K+-ATPase is stored in __________. When the parietal cell is stimulated by food, H+-K+- ATPase -bearing membranes vesicles fuse with the apical membrane of
the cell. On removal of the stimulus, the apical cell membrane is internalized into the cell to reform the cytoplasmic store of H+-K+-ATPase. The traffic of intracellular H+-K+-ATPase is dependent on _________, which is triggered by gastrin and acetylcholine.

Answer 25

H+-K+-ATPase; intracellular vesicles; calcium signaling

Question 26

Histamine from ECL cells binds to __________ on parietal cells and triggers HCl secretion by a _________ process. This process is suppressed by the hormone somatostatin and by PGE2.

Answer 26

H2 receptors; cAMP-dependent

Question 27

Acetylcholine released from vagal fibers act on __________ on parietal cells and activate calcium signaling. ACh directly activates acid secretion and also promotes trafficking of the proton pump to the apical membrane.

Answer 27

muscarinic M3 receptors

Question 28

Gastrin released from G cells in antral gastric glands act on gastrin receptors on _________ and activate calcium signaling. Gastrin directly activates acid secretion and also promotes trafficking of the proton pump to the apical membrane.

Answer 28

parietal cells

Question 29

Steps in Acid Secretion from Parietal Cells

1. H+ ions are produced inside the cell through the reaction of CO2. __________ plays a key role in this process.
2. H+ ions are secreted by the parietal cell through its apical membrane via the proton pump. ATP is required. It is electroneutral since H+ efflux is balanced by _____ entry.
3. HCO3- produced by step 1 is transported out of the parietal cell at the basolateral border in exchange for Cl- entry. The exchange is electroneutral. HCO3- transported out of the parietal cell enters the bloodstream and increases blood pH. After a meal, there is a rise in blood pH called the _______________.
4. __________ located on the basolateral membrane of the parietal cell, pumps out three Na+ ions for every two K+ ions pumped in. The interior of the parietal cell therefore becomes negative.
5. K+ ions that are pumped into the cell in step 4 diffuse out through K+ channels present on the basolateral as well as apical membranes. This efflux of K+ further increases ____________ of the parietal cell.
6. The high intracellular negativity forces out Cl- ions through Cl- channels located on the apical membrane.

Answer 29

Carbonic anhydrase; K+ ; postprandial alkaline tide.

Na+-K+ ATPase; intracellular negativity

Question 30

There are five neurohormonal mediators of gastric secretion. Three are stimulatory (ACh, gastrin, histamine) and two are inhibitory (somatostatin and PGE2). Receptors for each of these are present on parietal and ECL cells.
• Gastrin secretion from G cells is stimulated by ________________ released from vagal fibers, and inhibited by somatostatin and PGE2.
• Somatostatin (from D cells) inhibits acid secretion in two ways: 1) by inhibiting parietal cells and 2) indirectly by inhibiting _________. GRP augments acid
release by inhibiting somatostatin release. On the other hand, secretin, GIP, & VIP inhibit acid secretion by stimulating somatostatin release.
• ECL cells secrete histamine that stimulates HCl from parietal cells. ECL cells have receptors for gastrin, ACh and ______.
• Vagal stimulation: Vagal fibers to the stomach secrete gastrin-releasing peptide (GRP) and ___________.
• GRP increases gastrin secretion by G cells, and inhibits somatostatin from D cells, and thereby disinhibits HCl secretion by parietal cells.
• ACh increases acid secretion by inducing histamine release from ECL cells and by direct actions on parietal cells.

Answer 30

gastrin-releasing peptide (GRP); gastrin secretion; PGE2;

acetylcholine

Question 31

Inhibitors of acid secretion:

1. Acid in duodenum –> triggers ________ –> releases somatostatin –> ↓ gastrin –> ↓ HCl
2. Fatty acids in duodenum trigger _____________–> releases somatostatin –> ↓ gastrin –> ↓ HCl
3. ___________ chyme in duodenum –> stimulates duodenal osmoreceptors and chemoreceptors –> ↓HCl
4. Distention of duodenum –> stimulates duodenal mechanoreceptors –> ↓HCl

Answer 31

Secretin; Gastric Inhibitory Peptide (GIP) & VIP ; Hyperosmotic

Question 32

Phases of gastric acid secretion
• Inter-digestive phase: Circadian rhythm: peak at midnight, trough at 7:00 a.m.
• ________ phase: 35% of acid secreted after a meal
• __________ phase: 60% of acid secreted after a meal
• _____ phase: 5% of acid secreted after a meal

Answer 32

Cephalic; Gastric; Intestinal

Question 33

Inter-digestive phase: Acid is continually secreted by the stomach, even between meals and during sleep. Because most of the basal secretion is abolished by __________ (cutting the vagus), the inter-digestive gastric acid secretion is believed to be mediated by the vagus nerve

Answer 33

vagotomy

Question 34

Cephalic phase accounts for about 35-50% of acid secreted in response to a normal meal.
• Acid secretion is increased by the smell, taste and thought of food, chewing and swallowing, and psychic factors like anger and hostility. Acid secretion is decreased by depression and fear.
• Acid secretion is mediated by the vagus nerve directly (ACh from vagal nerve fibers acts on ____________ on parietal and ECL cells), and indirectly (______ from vagal fibers stimulate G cells to secrete gastrin, which then acts on the ECL and parietal cells).
• Hypoglycemia: hypoglycemia acts via the brain and vagal efferents to stimulate acid and _________ secretion.
• Alcohol: Moderate amounts of alcohol enhance the appetite (e.g. a glass of wine with dinner) because it acts directly on the gastric mucosa and increases gastric secretion.

Answer 34

M3 receptors; GRP; pepsin

Question 35

Gastric phase: The gastric phase starts when food makes contact with gastric mucosa. It accounts for about 60% of gastric acid secretion in response to a meal.

1. Distention of the orad stomach stimulates a ____________ (afferent and efferent through vagus nerve), which induces acid secretion directly (ACh acts on __________ on parietal and ECL cells), and indirect (GRP stimulate G cells to secrete gastrin, which then acts on the ECL and parietal cells to trigger acid secretion).
2. Distention of the antrum (as food moves from orad to the caudad part of the stomach) and reduction in ____________ (due to buffering of acid by food) triggers local reflexes involving the ___________. Release of ACh triggers G cells to secrete gastrin.
3. Amino acids and peptides produced by digestion (particularly ________________) directly stimulate G cells to secrete gastrin. Coffee and alcohol can also stimulate acid secretion during this phase.

Note: In patients with allergies, mast cells can infiltrate the stomach and release histamine when allergic foods are ingested. Histamine would act on histamine H2 receptors on parietal cells and increase acid secretion

Answer 35

vago-vagal reflex; M3 receptors; antral acidity; myenteric plexus

phenylalanine and tyrosine

Question 36

Intestinal phase accounts for about 5% of gastric acid secretion. When food enters the intestine, amino acids in the __________ (particularly __________________) travel by the blood stream to the stomach and directly trigger G cells to produce gastrin, which in turn induces HCl secretion.

Answer 36

duodenum; phenylalanine and tyrosine

Question 37

Basal acid output (BAO) is the rate of acid secretion in the absence of all avoidable stimulation.
• In the night-fasting secretion test, continuous gastric suction is performed through an indwelling nasogastric catheter from 9:00 p.m. to 9:00 a.m. The room is kept devoid of _________ Normally _____ of gastric juice is collected overnight. The HCl concentration in the juice gives the BAO = <10 mmol/h.

Maximal acid output (MAO) is the gastric secretion produced by stimulants such as ________ and histamine.
• The acid output is measured every 15 min for 1 h. MAO represents the total acid output over 1 h and is normally _______.
• The Peak acid output (PAO) is calculated by totaling the two highest consecutive 15 min outputs and multiplying by 2.

Answer 37

food or odor.; 400 ml

pentagastrin; < 50 mmol/h

Question 38

Zollinger-Ellison syndrome is a disorder characterized by the triad of severe (multiple) __________, gastric acid hypersecretion and a ________ (tumor that secretes gastrin from malignant G cells). Patients may also have diarrhea.

These tumors are usually found in the pancreas or duodenum. Unlike gastrin released from G cells in the antrum in response to normal physiological stimuli, gastrin released from gastrinomas is not under physiological control. A basal acid output of more than __________ is diagnostic of Zollinger-Ellison syndrome.

Maximal Acid Output will exceed normal values. Secretin suppresses gastrin secretion by normal G cells (via __________), paradoxically increases gastrin secretion from malignant G cells in gastrinomas

Answer 38

peptic ulceration; gastrinoma; 15 mEq/h; somatostatin

Question 39

Gastric mucous- a protective barrier
• Protects mucosa from auto-digestion, and mechanical and chemical damage.
• HCO3- secreted by mucous cells become trapped in the mucous gel, increase pH, and thereby reduce the corrosive action of gastric acid.
• Acid does not disrupt mucus layer, but crosses by creating ____________.

Answer 39

fine channels

Question 40

Digestive Functions of the Stomach

• _________: digests fats. Not a critical player in fat digestion except in pancreatic insufficiency when pancreatic lipase is deficient.
• Gastric acid (pH ~1): 1) Activates pepsin; 2) Dissolves insoluble iron salts in food. 3) Frees vitamin B12 from food allowing it to bind ______; 4) Disinfectant; 5) Stimulates the duodenum to secrete _____

Intrinsic factor released by parietal cells is essential for Vitamin B12 absorption.

Answer 40

Gastric Lipase; R-binder; Secretin.

Question 41

1. Heal ulcers by suppressing gastric acid secretion
• Antacids
• Histamine H2R antagonists
• Proton Pump Inhibitors
• \_\_\_\_\_\_\_\_\_\_\_\_

2. Heal ulcers by enhancing mucosal defense
   • __________
   • Bismuth compounds
3. Treat H. pylori infection
   • Triple or quadruple therapy

Answer 41

Potassium-competitive acid blockers (P-CABs); Sucralfate

Question 42

Requirements of a good antacid: 1) potent in neutralizing gastric acid, 2) not absorbed from the GI tract, 3) inexpensive and 4) contain negligible amounts of ________. The most widely used preparations are mixtures of aluminum hydroxide and magnesium hydroxide. Al(OH)3 causes _______, while Mg(OH)2 is a ________, but when combined they counteract each others effect (e.g. Gelusil, Mylanta extra strength, Maalox TC).

Mg(OH)2 (Milk of Magnesia): Potent antacid, which neutralizes HCl with the production of MgCl2 and H2O. Magnesium trisilicate: slow-acting weak antacid.

Al(OH)3: Neutralizes hydrochloric acid with the production of AlCl3 and H2O.

Calcium carbonate (CaCO3): Potent and inexpensive antacid, which neutralizes HCl with the production of CaCl2 and H2O.

Sodium bicarbonate (Alka Seltzer, NaHCO3): Potent, rapidly acting and inexpensive antacid but is not used as an antacid for _________.

Answer 42

sodium; constipation; laxative;

peptic ulcer disease

Question 43

H2 Receptor antagonists
• H2 receptor antagonists block _________acid secretion.
• Since Gastrin and ACh stimulate ECL cells to secrete histamine, H2 receptor antagonists partially suppress HCl secretion induced by gastrin and ACh.
• H2 receptor antagonists suppress __________ more effectively than food-stimulated acid secretion. (given preferably at night).

Mechanism of action
• Inhibit production of gastric acid secretion by reversibly competing with histamine for binding to histamine H2 receptors on the ___________ of parietal cells.

Common H2 receptor antagonists
• __________ has the most side effects (5% of patients).
• Ranitidine (Zantac): 4-10 times more potent than Cimetidine; safe.
• Nizatidine (Axid, Tazac): 4-10 times more potent than Cimetidine; safe.
• Famotidine (Pepcid): 20-50 times more potent than Cimetidine; safe.

Answer 43

histamine-induced; nocturnal acid secretion

basolateral membrane;

Cimetidine (Tagamet)

Question 44

• PPIs are weak bases that diffuse into the parietal cell where they become protonated and concentrated. They are non-functional at neutral pH.
• At acidic pH (pH 5), PPIs change into _____________________, which interact with sulfhydryl groups in ___________ and irreversibly inactivate it.

Common PPIs: Omeprazole, Pantoprazole, Lansoprazole, Rabeprazol, Esomeprazole

1. Duration of action ~ 24 h; may require 2-3 days to achieve full effectiveness.
2. PPIs should be taken before a meal, and preferably before the first meal of the day.
3. They are enteric coated tablets that dissolve in the intestine and then travel by the blood stream to parietal cells.

PPIs effective in suppressing acid secretion throughout the day, less effective nocturnally. Must be taken at least 30 min before a meal.

Answer 44

sulphenamide/sulphenic acid; H+-K+-ATPase

Question 45

PPIs: Conventional PPI are ________, which must be protonated to become active. The PPI must first get absorbed in the small intestine, then travel by blood to the parietal cells where protonation of the PPI occurs. This process takes time. PPIs drug must be taken ________ before the meal. After absorption, the T1/2 in plasma is short, approximately _____ for conventional PPIs.

Answer 45

prodrugs; 30 min; 2 h

Question 46

P-CAB: Can be taken regardless of meal ingestion and the rate of absorption is not affected by meals. The absorption speed of P-CABs are rapid, and the time taken to reach maximum concentration in plasma is less than 2 h after oral administration. After absorption, the T1/2 in plasma is approximately 9 hours for vonoprazan, a P-CAB. Therefore, vonoprazan stays in the blood longer and can block acid secretion for longer periods. Other P-CABs = _________________

Answer 46

Revaprazan, Tegoprazan.

Question 47

Comparison of mechanisms of action of lansoprazole (conventional proton pump inhibitor) and vonoprazan (potassium competitive acid blocker).
• (H+, K+)-ATPases are located in tubulovesicles in
quiescent parietal cells and appear on the apical
membrane of secretory canalicus in the active phase, which occurs after a meal.
• PPI / Lansoprazole converts to its active form in the secretory canaliculus, though it degrades soon after. The active form of lansoprazole binds __________ to H+, K+-ATPase.
• P-CAB / Vonoprazan stably accumulates in the ______________ and non-covalently binds to H+, K+-ATPase with a slow dissociation rate and inhibits newly exposed H+, K+-ATPase.

Answer 47

covalently; acidic secretory canaliculus

Question 48

Heal by enhancing mucosal defense

• Sucralfate [Sucrose sulfate + poly Al (OH)3]
‒ At pH <4, polymerizes to form _________, coats ulcers better than normal mucosa, provides physical barrier to acid and pepsin
‒ Taken on an empty stomach 1h before meals, 4 times/day
‒ Constipation: most common side effect

• Bismuth colloidal compounds
‒ enhances secretion of mucus and __________
‒ ________ action against Helicobacter pylori

Answer 48

viscous gel; bicarbonate; Antibacterial

Question 49

Sucralfate, a complex salt of ________- and poly-aluminum hydroxide, appears to be as effective as H2RAs in healing duodenal ulcers, but it appears less effective in treating gastric ulcers. Sucralfate has little or no effect on gastric acid secretion and no acid neutralizing activity. At pH<4 in the stomach, sucralfate becomes a gel-like substance that binds preferably to defective mucosa compared to normal mucosa. It coats ulcer craters and acts as a physical barrier to the diffusion of acid, pepsin, and _____.

Answer 49

sucrose sulfate; bile acids

Question 50

Bismuth: In the stomach, bismuth forms ____________, which enhance secretion of mucus and bicarbonate and protect ulcers from acid-pepsin digestion. Bismuth-protein complexes have little acid-neutralizing effect and do not reduce gastric secretion. Bismuth-containing compounds are used as part of therapy cocktails to treat Helicobacter pylori infection because this heavy metal’s antimicrobial activity is linked to its effect on bacterial iron uptake.

Answer 50

bismuth-protein complexes

Question 51

Treat H. pylori infection
• BMT triple therapy: Bismuth + Metronidazole + Tetracycline
• LAC: Lansoprazole + _________+ _________
• OAC: Omeprazole + Amoxicillin + Clarithromycin
• RBC-AC: __________________ + Amoxicillin + Clarithromycin
• MOC: ___________ + Omeprazole + Clarithromycin

• Quadruple therapy:
‒ Bismuth subcitrate, PPI, Metronidazole, Tetracycline
‒ Bismuthate dicitrate, Esomeprazole, Levofloxacin, Tetracycline
‒ Omeprazole, Metronidazole, Amoxicillin, Clarithromycin

Clarithromycin, an acid stable macrolide antibiotic, exhibits effective antimicrobial activity against Helicobacter pylori (H pylori), and is therefore included in many of the treatment regimens.

Answer 51

Amoxicillin + Clarithromycin;

Ranitidine-bismuth citrate;

Metronidazole

Question 52

NSAIDs (Non-Steroidal Anti-inflammatory Drug) are inhibitors of ______________. NSAIDs reduce the generation of PGE2 from ____________. Hence the brake on acid secretion (PGE2) is lost. Also, there is less protection from acid because less mucous and bicarbonate is made. The result is severe peptic ulceration, often seen in patients who over-use NSAIDs.

Answer 52

cyclooxygenase enzymes; arachidonic acid

Question 53

Gastroparesis: Syndrome characterized by delayed gastric emptying resulting in impaired transit of food from the stomach to the duodenum in the absence of mechanical obstruction. ________ is most common cause of gastroparesis.

Answer 53

Diabetic gastroparesis

Question 54

Metoclopramide activates ___________ in Vagal neurons and inhibits D2-receptors on neurons in the ____________. It also inhibits D2-receptors centrally. Metoclopramide is one of the oldest drugs used
for the treatment of diabetic gastroparesis. Its use is limited by CNS side-effects in as many as 40% of patients.
• Side effects: _____ crosses the blood-brain barrier and therefore causes many neurological adverse effects, particularly extrapyramidal signs in young adults and children e.g. oculogyric crisis. They develop dystonia which can be treated with ____________. __________ that develops with chronic treatment can be irreversible. Metoclopramide may be the commonest cause of drug-induced movement disorder. Other side effects include drowsiness, anxiety, fatigue, insomnia, agitation and restlessness.

Answer 54

5HT4-receptors; Myenteric Plexus; Reglan; benztropine (Cogentin); Tardive dyskinesia

Question 55

Domperidone: Domperidone, a central and_____ peripherally-acting inhibitor is
another prokinetic, which does not cross the blood-brain barrier and therefore has less CNS side effects

Answer 55

D2R

Question 56

Erythromycin: Erythromycin, a ________ antibiotic that stimulates smooth muscle motilin receptors, may dramatically improve gastric emptying in patients with severe diabetic gastroparesis when given intravenously. Long term use of the
drug is of limited efficacy.

Answer 56

macrolide