GIT (Drugs For Motility Disorders and Irritable Syndrome) Flashcards
Drugs that can selectively stimulate gut motor function
(prokinetic)
DRUGS FOR MOTILITY DISORDER
drugs that increases ____________ pressure may be
useful for GERD
lower esophageal sphincter pressure
Increase lower esophageal sphincter pressure may be
useful for
GERD
Improves gastric emptying may be helpful for ________ and ________
gastroparesis; post surgical gastric emptying delay
CHOLINOMIMETICS will reduce ________
LES sphincter tone
Stimulate muscarinic M3 receptor on muscle cell and at
myenteric plexus synapse
BETANECHOL
BETANECHOL is used in the past for the treatment of _______ and
____________
GERD and gastroparesis
Used in the past for the treatment of GERD and
gastroparesis
BETANECHOL
T/F: Betanechol is no longer used due to toxic effect
T
Motility Disorder Drugs that is also an Acetylcholinesterase inhibitor
NEOSTIGMINE
what does NEOSTIGMINE inhibits
Acetylcholinesterase
Can enhance gastric and small intestine and colonic
emptying
NEOSTIGMINE
Administration of ______ of Neostigmine may lead to evacuation of the feces
2mg
Side Effects of Neostigmine
○ Excessive salivation
○ Bradycardia
○ Nausea
○ Vomitting
○ Diarrhea
Used in hospitals for acute bowel distention
NEOSTIGMINE
Activation of dopamine receptor inhibits ________________ therefore its blockade is
believed to be the primary prokinetic mechanism
cholinergic
smooth muscle stimulation
primary prokinetic mechanism
blockade of cholinergic smooth muscle stimulation caused by the activation of dopamine receptor
Movement in the GI is faster if _________ is blocked
dopamine
D2 blockade causes (increase/decrease) bowel transit
increased
METOCLOPROMIDE (can/cannot) cross the blood brain barrier (BBB)
can
Blocks D2 receptor in the chemoreceptor trigger zone
(CTZ) of the medulla, resulting in potent antinausea and
antiemetic action
METOCLOPROMIDE
METOCLOPROMIDE blocks D2 receptor in the chemoreceptor trigger zone
(CTZ) of the medulla, resulting in potent _______ and ________ action
potent antinausea and
antiemetic action
Metoclopromide blocks D2 receptor in the _______________ of the medulla, resulting in potent antinausea and
antiemetic action
chemoreceptor trigger zone
(CTZ)
May also cause parkinsonian symptoms (dystonia,
akathisia, parkinsonian)
METOCLOPROMIDE
D2 Antagonist that does not cross the blood-brain barrier; less likely to cause
CNS effects
DOMPERIDONE
T/F: Domperidone does not have anti-emetic property
T
only improves motility → transit of the bowel
DOMPERIDONE
MOTILIN RECEPTOR AGONISTs
Erythromycin
Erythromycin is classified under ________ antibiotics
macrolides
Stimulates the motilin receptors on gastrointestinal
smooth muscle and promote the onset of a migrating motor
complex
Motilin Receptor Agonist (Erythromycin)
Motilin Receptor Agonist stimulates the motilin receptors on gastrointestinal
smooth muscle and promote the onset of a _______________
migrating motor
complex
form and dose of erythromycin that is beneficial in some patients
with gastroparesis
IV erythromycin (3 mg/kg)
Used in patients with acute upper gastrointestinal
hemorrhage to promote gastric emptying of blood before
endoscopy
Motilin Receptor Agonist (Erythromycin)
ADRs of Motilin Receptor Agonist (Erythromycin)
Diarrhea
Gastroparesis
T/F: Tolerance can be rapidly developed in Erythromycin
T
LAXATIVES
BULK FORMING LAXATIVE
STOOL SURFACTANT AGENTS (SOFTENER)
OSMOTIC LAXATIVE
BALANCED POLYETHYLENE GLYCOL
STIMULANT LAXATIVE
DIPHENYLMETHANE DERIVATIVE
BULK FORMING LAXATIVEs
Psyllium, Methylcellulose, Polycarbophil
Indigestible, hydrophilic colloids that absorb water,
forming bulky, emollient get that distends the colon and
prompt peristalsis
BULK FORMING LAXATIVE (Psyllium, Methylcellulose, Polycarbophil)
STOOL SURFACTANT AGENTS (SOFTENER)
Docusate, glycerin and mineral oil
Soften stool material, permitting water and lipids to
penetrate
STOOL SURFACTANT AGENTS (Docusate, glycerin and mineral oil)
STOOL SURFACTANT AGENTS May be administered _________ or ________
orally or rectally
lubricates fecal material, retarding water
absorption from the stool
Mineral oil
Used to prevent the impaction of the fecal matters
Mineral oil
Long term use impairs absorption particularly insoluble
vitamins (Vit. A, D, E, K
STOOL SURFACTANT AGENTS (Docusate, glycerin and mineral oil)
Soluble but nonabsorbable compound (sugar) that result
in increased stool liquidity due to an obligate increase in
fecal flui
OSMOTIC LAXATIVE
Nonabsorbable sugar or salt (Osmotic Laxative) is used for the treatment of ________ or the prevention of ________
acute constipation or the
prevention of chronic constipation
Commonly used osmotic laxative
Magnesium hydroxide (Milk of Magnesia)
Magnesium hydroxide should not be used for prolonged period in
patients with _______________ due to the risk of
hypermagnesemia
renal insufficiency
Nonabsorbable sugar that can be used to prevent
or treat chronic constipation
Sorbitol and Lactulose
Sorbitol and Lactulose are metabolized by ____________
producing severe flatulence and cramps
colonic bacteria
These sugar are metabolized by colonic bacteria
producing severe flatulence and cramps
Sorbitol and Lactulose
High doses of osmotically active agents produces
prompt bowel evacuation within
1 to 3 hours
May be used for the treatment of acute constipation or
to cleanse the bowel prior to medical procedure
OSMOTIC LAXATIVE
infrequently used osmotic laxative due to the
risk of hyperphosphatemia
Sodium phosphate
Osmotic Laxatives
- Absorbable sugars
- Nonabsorbable sugars:
* Magnesium hydroxide (Milk of Magnesia)
* Sorbitol and Lactulose
* Sodium phosphate
Used for complete colonic cleansing before
gastrointestinal endoscopic procedure
BALANCED POLYETHYLENE GLYCOL
Inert, nonabsorbable, osmotically active sugar (PEG) with
sodium sulfate, sodium chloride, sodium bicarbonate and
potassium chloride
BALANCED POLYETHYLENE GLYCOL
Designed so that no IV fluid and electrolyte shift will occur
BALANCED POLYETHYLENE GLYCO
For opitmal bowel cleansing ____ to ______ liters of BALANCED POLYETHYLENE GLYCOL solution should be ingested rapidly (over 1 to 2 hours) on the evening before
the procedure and again in ___ to ___ hours before the
procedure.
1 to 2 L; 4 to 6 hours
For treatment or prevention of chronic constipation,
smaller doses of _____________ may be mixed with water or
juice (17 g/8 oz)
PEG powder
Induce bowel movements through a number of poorly
understood mechanisms
STIMULANT LAXATIVE
Direct stimulation of the enteric nervous system and
colonic electrolyte and fluid secretion
STIMULANT LAXATIVE
Anthraquinone Derivative
STIMULANT LAXATIVE
Anthraquinone Derivative (plants)
Aloe, senna, cascara sagrada
Poorly absorbed and after hydrolysis in the colon,
produce a bowel movement in 6 to 12 hours when given
orally and within 2 hours when given rectall
Anthraquinone Derivative
Chronic use of Anthraquinone Derivative causes __________
melanosis coli
Carcinogenic
Anthraquinone Derivative
DIPHENYLMETHANE DERIVATIVEs
Bisacodyl (Dulcolax)
Bisacodyl is used for the treatment of ________ and ________
acute and chronic constipation
Used in conjunction with PEG solution for colonic cleansing
prior to colonoscopy
DIPHENYLMETHANE DERIVATIVE (Bisacodyl)
Bisacodyl Induces bowel movement within ______ to _______ hours when given
orally and ______ to ______ minutes when taken rectally
6 to 10 hours orally; 30 to 60 rectally
CHLORIDE CHANNEL ACTIVATORs
LUBIPROSTONE
LINACLOTIDE
Prostanoic acid derivative labeled for use in chronic
constipation and irritable bowel syndrome (IBS)
LUBIPROSTONE
Stimulating the type 2 chloride channel (CIC-2) in the
small intestine
LUBIPROSTONE
LUBIPROSTONE stimulates the _________ in the
small intestine
type 2 chloride channel (CIC-2)
Increases the chloride rich fluid secretion into the intestine,
which stimulate intestinal motility and shortens intestinal
transit time
LUBIPROSTONE
LUBIPROSTONE increases the _______ rich fluid secretion into the intestine,
which stimulate intestinal motility and (shortens/lengthens) intestinal
transit time
chloride; shortens
_________ mcg of LUBIPROSTONE orally ______ daily is recommended dose for
treatment of chronic constipation
24; twice
T/F: There is no loss of efficacy if Lubiprostone is taken as long term therapy
T
Minimally absorbed Chloride Channel Activator
LINACLOTIDE
14 amino acid peptide that stimulates intestinal chloride
secretion through a different mechanism
LINACLOTIDE
LINACLOTIDE is approved for the treatment of chronic constipation
and _____________
IBS with predominant constipation
Binds to and activates guanylyl cyclase-C on the luminal
intestinal epithelial surface, resulting in increased
intracellular and extracellular cGMP that leads To
activation of the cystic fibrosis transmembrane
conductance regulator (CFTR) leading to increased
chloride rich secretion and acceleration of intestinal transit
LINACLOTIDE
LINACLOTIDE binds to and activates guanylyl cyclase-C on the ____________, resulting in ______(increased/decreased)
intracellular and extracellular cGMP that leads To
activation of the ________________leading to increased
chloride rich secretion and acceleration of intestinal transit
luminal
intestinal epithelial surface; increased; cystic fibrosis transmembrane
conductance regulator (CFTR)
OPIOID RECEPTOR ANTAGONIST
METHYLNALTREXONE BROMIDE AND ALVIMOPAN
Acute and chronic therapy with opioids may cause
___________ by decreasing intestinal motility, which
results in _________ transit time and _________ absorption of
fecal water
constipation; prolongs; increased
METHYLNALTREXONE BROMIDE AND ALVIMOPAN (Do not readily cross/ Readily cross) the blood-brain barrier
Do not readily cross the blood-brain barrier
inhibit peripheral µ-opioid receptor without
impacting analgesic effects within the CNS
METHYLNALTREXONE BROMIDE AND ALVIMOPAN
METHYLNALTREXONE BROMIDE AND ALVIMOPAN inhibit peripheral µ-opioid receptor _____(with/without)
impacting analgesic effects within the CNS
without
Treatment of opioid induced
constipation; administered SQ (0.15 mg/kg) every 2 days.
Methylnaltrexone
Short term used to shorten the period of
postoperative ileus in hospitalized.
Alvimopan
Opiod antagonist that have cardiotoxic effect
Alvimopan
Opiod antagonist that doesnt have pschological/CNS effects
Methylnaltrexone
SEROTONIN 5-HT4 RECEPTOR AGONISTs
TEGASEROD
PRUCALOPRIDE
Stimulation of ____________ on the presynaptic terminal
of submucosal intrinsic primary afferent nerves enhances
the release of their neurotransmitters, including __________, which stimulates second order enteric
neurons to promote the__________
5-HT4 receptor; gene
related peptide; peristaltic reflex
Serotonin 5-HT4 partial agonist that has high affinity for
5-HT4 receptor but no appreciable binding 5-HT3 or
dopamine receptor
TEGASEROD
TEGASEROD is approved for the treatment of patients with chronic
constipation and ______________
IBS with predominant constipation
High affinity 5-HT4 agonist available in Europe
PRUCALOPRIDE
PRUCALOPRIDE is used as treatment for chronic constipation in ______
women
ANTIDIARRHEAL treats _______
Mild to moderate diarrhea
Can Antidiarrheals be used for patients with bloody diarrhea, high fever and systemic toxicity?
No, If given, it can worsen underlying conditions becase it increases the colonic phasic activity inhibiting the
stimulation of the GI
OPIOID AGONISTs
Loperamide
Diphenoxylate
Kaolin
Pectin
Combined: Kaolin-Pectin
Increase colonic phasic segmenting activity through
inhibition of presynaptic cholinergic nerve in the
submucosal and myenteric plexuses and lead to increased
colonic transit time and fecal water absorption.
OPIOID AGONIST
Opioid agonist that does not cross the blood-brain
barrier
Loperamide
Opioid agonist that has no analgesic properties or potential addiction
Loperamide
Prescription opioid agonist that has no analgesic
properties in standard doses
Diphenoxylate
Higher doses have CNS effect, and prolonged use can
lead to opioid dependence
Diphenoxylate
Naturally hydrated magnesium aluminum silicate
Kaolin
Indigestible carbohydrate from apple
Pectin
Absorbs bacterial toxin and fluids
Pectin
T/F: Combined: Kaolin-Pectin may interfere with the absorption of other drugs
T
T/F: Combined: Kaolin-Pectin can cause constipation
T
Conjugated bile salt normally absorbed in the terminal
ileum
BILE SALT BINDING RESIN
BILE SALT BINDING RESINs
Cholestryramine, Colestipol and Colesevelam
BILE SALT BINDING RESIN is normally absorbed in the
terminal
ileum
May decrease diarrhea caused by excess fecal bile acid
BILE SALT BINDING RESIN
BILE SALT BINDING RESIN ADRs
○ Bloating
○ Flatulence
○ Constipation
○ Fecal impaction
OCTREOTIDEs
SOMATOSTATIN
T/F: Somatostatin is not a statin
T
14 amino acid peptide that released in the gastrointestinal
tract and pancreas from paracrine cell, D cells and enteric
nerve as well as from hypothalamus
SOMATOSTATIN
nhibits the secretion of numerous hormones and
transmitter including gastrin, cholestykinin, growth
hormones
SOMATOSTATIN
SOMATOSTATIN inhibits the secretion of numerous hormones and
transmitter including ______, __________, ____________
gastrin, cholestykinin, growth
hormones
Reduces intestinal fluid secretion and pancreatic secretion
SOMATOSTATIN
Slows gastrointestinal motility and inhibits gallbladder
contraction
SOMATOSTATIN
Reduces portal and splanchnic blood flow
SOMATOSTATIN
Inhibits secretion of some anterior pituitary hormone
SOMATOSTATIN
Clinical usefulness of somatostatin is limited by its ________( short/long)
half-life in the circulation
short
Somatostatin can inhibit _________ and reduce __________:
Inhibits:
-secretion of numerous hormones and
transmitter including ___________________
secretion of _________________
Reduces
- _____________ secretion and ________ secretion
- _________ and _________ blood flow
Inhibits:
-secretion of numerous hormones and
transmitter including gastrin, cholestykinin, growth
hormones
-secretion of some anterior pituitary hormone
Reduces
- intestinal fluid secretion and pancreatic secretion
- portal and splanchnic blood flow
an idiopathic chronic, relapsing disorder
characterized by abdominal discomfort (pain, bloating,
distention or cramps) in association with alterations in
bowel habits (diarrhea, constipation
IBS
Pharmacologic therapy for IBS are directed at __________ and __________
relieving
abdominal pain and discomfort and improving bowel
function
ANTISPASMODIC (ANTICHOLINERGIC) Drugs
Dicyclomine and Hyoscyamine
Works primarily through anticholinergic activities
ANTISPASMODIC (ANTICHOLINERGIC)
Inhibits muscarinic cholinergic receptor in the enteric
plexus and on smooth muscle
Dicyclomine and Hyoscyamine
Used to relieve abdominal pain
Dicyclomine and Hyoscyamine
At lower dose, Dicyclomine and Hyoscyamine exhibits
minimal autonomic effect
At a higher dose, Dicyclomine and Hyoscyamine exhibits
significant anticholinergic effect
activate
visceral afferent pain sensation via extrinsic sensory
neurons from the gut to the spinal cord and central
nervous system
5-HT3 receptor
Inhibition of afferent gastrointestinal 5-HT3 receptor may
_____(increase/reduce) unpleasant visceral afferent sensation, including
nausea, bloating and pain
reduce
Highly potent and selective antagonist of the 5-HT3
receptor
Alosterin
Alosterin is rapidly absorbed from the gastrointestinal tract with a
bioavailability of 50 to 60%, and has a plasma half-life of
____________ but a much longer duration of effect
1.5 hours
Alosterin undergoes extensive _____________ with renal excretion of most metabolite
hepatic cytochrome P450
metabolism
Alosterin binds with ________ affinity and dissociates _________ from
5-HT3 which accounts for its long duration of action
higher; more slowly
Alosterin is approved for the treatment of women with __________ in
whom diarrhea is the predominant symptoms
severe IBS
Drugs that are approved for the treatment of chronic constipation
and IBS with predominant constipation
LINACLOTIDE
TEGASEROD
Alosterin (for women)
