92 - GI drugs Flashcards
Peristalsis is initiated by which 4 things?
- Volume distension
- Change in pressure (stretching)
- Hyperosmolarity
- Digestion product
Peristalsis is achieved when disruption or pressure releases ________ from enterochromaffin cells.
5-HT
How can peristalsis be abolished?
6 ways
- Removing the mucosa (where the pressure receptors are located)
- Ganglionic blocking drugs
- Muscarinic antagonists
- Opioids
- Stimulation of extrinsic postganglionic sympathetic nerves
- Local anaesthetics
When are drugs that increases motility of the gut used?
A. Empty bowel after surgeries B. Prior to endoscopy C. Counteract constipation side effects of other drugs D. Remove parasites E. Remove bacteria
B,C,D
A. Should be before surgery
E. no such thing
Drugs that treat GERD aims to ________ sphincter tone and ________ LES.
increase;
contract
Which 4 pharmacological classes are used to treat GERD? Give example of drugs of each class.
- Muscarinic agonist
- Bethanechol - Dopamine receptor blocker
- Domperidone, metoclopramide (D2 antagonist) - Proton Pump Inhibitor
- Omeprazole, pantoprazole - H2 antagonists
- Cimetidine, Ranitidine
How does muscarinic agonists like bethanechol treat GERD?
It increases GI motility,
used with 5-HT4 agonists
How does Dopamine receptor blocker like domperidone and metaclopramide treat GERD?
It increases sphincter tone
(as dopamine relaxes sphincter)
Metoclopramide increases motility as well.
What effect do PPI and H2 antagonists have on GERD patients?
Reduce acid secretion
Name the 3 pharmacological classes which increases motility of the gut. Give examples of drugs of the class.
- 5-HT4 agonist
- Metoclopramide (D2 antagonists)
- Cisapride, mosapride, prucalopride
(唔-hightea 四個人=四隻藥， caesar salad pride, no sand pride, 呸calories pride）
- Motilin receptor agonist
- Erythromycin
(non-antibiotic agonist, treat diabetic gastroparesis) - Ghrelin
- ipamorelin
- anamorelin
(究竟who more lin？）
ipa/ ana
How does 5-HT4 agonists like metoclopramide increase gut motility?
- They increases sensitivity of reflex to luminal content;
Peristalsis starts more easily. - Achieved by increasing cAMP of neurons, thus increasing acetylcholine releases from ENS
How does motilin receptor agonist like erythromycin increase gut motility?
It acts on smooth muscles receptor and is not blocked by TTX or muscarinic receptor antagonists.
> Migrating motor complex (MMC)
How does ghrelin like ipamorelin increase gut motility?
Via M receptors
and tachykininergic mechanism (NK1)
- promotes feeding and weight gain via growth hormone secretagogue receptors (GHS-R)
- Effect of feeding is mediated through the hypothalamus
Metoclopramide
A. is a D2 agonist
B. is a weak full 5-HT4 receptor agonist at low dose
C. is a strong 5-HT3 receptor agonist and weak 5-HT4 agonist at high dose
D. As PA2 decreases, activates more receptors together (both 5-HT3 and 4)
B and D only
A. is a D2 antagonist (because dopamine relaxes sphincter)
C. at high dose 5-HT3 antagonist
weka 5-HT4 agonist
D. Lower PA2 means lower specificity
Cisapride
A. is a selective 5-HT4 full agonist
B. will cause heart arrythmias when used together with P450 inhibitor
C. is withdrawn in most countries
All
How 5-HT4 receptor agonists facilitate acetylcholine release?
5-HT4 receptor agonists like metoclopramide are positively coupled to adenylate cyclase. With more adenylate cyclase to catalyse ATP > cAMP,
increases cAMP in cholinergic neuron, thus makes it easier to release acetylcholine to act on M3 muscarinic receptors on smooth muscles
therefore easier to achieve peristalsis.
What receptors are negatively coupled to adenylate cyclase?
What activates these receptor?
alpha 2 receptors
Noradrenaline and clonidine,
decreases cAMP,
Closure of Ca2+ channels, more difficult to release Ach
Which of the following are treatments to cause constipation?
A. COX (analgesics) B. Antacids C. Anticholinergics D. Barium sulphate E. Corticosteroids F. Diuretics G. Ganglionic blockers H. Laxatives (chronic) I. MAO inhibitors J. Propranolol K. Verapamil
All of the above
CAUSING CONSTIPATION
E. Corticosteroids prevents arachidonic acids to form PG
J. Propranolol (beta blockers, b1&2)
K. Verapamil (CCB for hypertension)
Laxative drugs are substances that loosen stools and increase bowel movements.
Name the 3 pharmacological classes of laxative drugs. Give examples of all of them .
- Bulk and osmotic laxatives
- Bulk: Methylcellulose, Bassorin, Metamucil
- Osmotic: MgSO4, Na2SO4, Mannitol, Lactulose
- Irritant or stimulant laxative
- Bisacodyl, phenolphthalein, Sennatoside*
DDI: enhance effect of digoxin by reducing serum K+ levels
- Fecal softeners (lubricant laxatives)
- Sodium dioctyl suphosuccinate
- liquid parrifin
Which kind of laxative have the fastest onset?
Osmotic laxatives: 1-3 hours
Irritant/stimulant laxatives: 6-8 hours
Bulk laxatives: 1-3 days
(stretching of wall facilitates peristalsis to provide laxative action, flatulence = farting is common)
How do Irritant/stimulant laxatives work?
- Stimulate sensory nerve endings in mucosa/ myenteric plexus
- Osmotic action, inhibition of Na+/K+ pump, increases ions secretion
- increases PG synthesis and elevates cAMP promoting secretion / motility.
How do lubricant laxatives / faecal softeners work?
- a surfactant that draws water into the faecal mass
- soften stool but not commonly used as may interfere with vitamin absorption
Name the 2 pharmacological classes that is for ant-diarrhea. Give examples.
- Aspirin
- Bismuth salicylate
- Subsalicylate - Opioid agonist
- Codeine
- Loperamide and Diphenoxylate
Other than aspirin and opioid agonists, what can be used as anti-diarrhea drugs? What are their actions?
- Kaolin
- Dioctahedral Smectite
- Activated Charcoal/Carbon
- Provides a surface to adsorb toxins and/or fluid
- For mild to moderate diarrhea
