27 - GI Pharmacology Flashcards
Gastric Secretion
Acid is secreted from
Gastric Parietal Cells
stimulated by:
Histamine / Acetylcholine / Gastrin
which all share a final-common pathway:
activate H+/K+ ATPase Proton Pump
- *Prostaglandin E2 & E2**
- *Function**
INHIBIT ACID
Stimulate Secretion of:
Mucus & Bicarbonate
DILATE mucosal blood vessels
REDUCE INTRAGASTRIC ACIDITY
Pharmacological Mechanisms for treating PUD
Block Gastric Acid secretion
multiple mechanisms
- *Neutralize Excess Gastric Acid**
- *antiacids**
- *Eradicate H.Pylori**
- *antimicrobials**
PROMOTE MUCOSAL DEFENSE
Pharmacological Mechanisms for treating PUD
- *Repair Mucosal Barrier Breakdown**
- *Cytoprotectants**
Prostaglandin-Stimulated Cytoprotection
Prostaglandin - analogs
ALSO reduce gastric acid secretion
H2RA
MoA
-tidine
- *Competitive Antagonist of H2 Receptor**
- virtually NO h1 Antagonist*
Inhibit GASTRIC ACID secretion
from Histamine / Analogues / Food
reduce:
Volume of GA secretion / H+ concentration
Gastrin / Pepsin / IF secretion
H2RA
ADR / Side Effects
-tidine
Cimetidine = many DI’s
Usually MINOR side effects
Microorganisms
from BASIC/hypoChloridic Stomach
Bradycardia –> Rapid IV, not usually givin IV though
CNS-Mental Confusion
- *PPI**
- *MoA**
PRODRUG
needs acidic environment –> absorbed in intestine
forms Disulfide bridge w/
H+ /K+ -ATPase Enzyme
Proton Pump
VVVVV
Decrease Gastric Acid Secretion
PPI
ADR’s
- Relatively MINIMAL side effects:*
- HA / Nausea / Diarrhea / Ab pain / Rash*
Potential for mucosal hyperplasia
- *Concerns about LONG TERM use**
- *Dementia?**
- *rebound HYPERacidity** –> TAPER OFF
DI’s –> other drugs that decrease acid secretion
- *CNS ACTIVE**
- *Anti-Muscarinics**
ATROPINE
SCOPOLAMINE
CNS inactive
probantheline / methscopolamine / glycopyrolate
Antimuscarinics
Scopolamine / Atropine
MoA
Block M1 & M3 Cholinergic Receptors
M1 –> histamine containing paracrine cells
M3 –> on parietal cells
most are non-selective
do NOT totally inhibit gastric acid secretion
LEAST effective class of antisecratory agents
usually used in tandem / with another drug
AntiMuscarinics
Scopolamine / Atropine
ADRs
Peripheral PARA-Sympatholytic Activity
Tachy Cardia // Constipation // Blurred Vision
drying/slowing
- *CNS** if it crosses BBB
- *sedation / memory disruption**
Types of Antacids
SCAMM
Systemic –> bloodstream
•Sodium bicarbonate
•Calcium bicarbonate
non-systemic –> poorly absorbed from intestine
•Aluminum hydroxide
•Magnesium hydroxide
•Magnesium trisilicate/Aluminum trisilicate
Antacids
MoA
CHEMICAL NEUTRALIZATION of Gastric HCL
RAISE pH of stomach contents
thereby
decreasing acid load –> to duodenum
& reducing PEPSIN activity
FAST ACTING // Short duration
Systemic Antacids
Sodium Bicarbonate >> Calcium Bicarb
Are ABSORBED –> BLOODSTREAM
so they have a potential to:
Increase blood pH & alkalinize URINE
hazardous if used chronically
days - weeks
Non-Systemic Antacids
Mg & Al
Hydroxide
POORLY absorbed from SMALL INTESTINE
so they are NOT
likely to alter BLOOD / URINE pH
Misoprostol = Cytotec
Class // MoA
Prostaglandin Analog
synthesized in GI mucosa –> reduce gastric acid production by:
inhibiting AC synthesis of cAMP
Stimulate secretion of mucus = Cytoprotectant
Used WITH NSAIDS to Prevent ULCER Formation
NSAIDS –> inhibit produciton of PG’s & cause ulcers
Prostaglandin Analog
Misoprostol = Cytotec
ADR
GI Cramping & Diarrhea
increased secretory activity –> accumulation of fluid in bowel
- *Increases UTERINE CONTRACTIONS
- NOT FOR PREGNANT WOMEN***
Sucralfate = Carafate
Class // MoA
CYTOPROTECTANT
Al-Sucrose-Sulfate
Basic –> @pH 4 –> polymerizes to from a viscous gel
- *Complexes w/ proteins** on ulcer surface to form a
- *PROTECTIVE LAYER** against:
- *HCL / PEPSIN / BILE**
inhibits PEPSIN activity & absorbs BILE ACIDS
Cytoprotectant
Sucralfate = Carafate
PK & Uses
- POORLY Absorbed from GI TRACT*
- *GOOD = want to COAT**, not absorb
6-12 hours
Increases rate of PEPTIC ULCER HEALING
efficacy is comparable to H2RA’s
Bismuth Subsalicylate = Pepto Bismol
MoA
Binds to an ulcer base –> providing Protective Coating
INCREASES SECRETION of:
Prostaglandin // Mucus // BiCarbonate
- REDUCES H. PYLORI*
- *antimicrobial**
Bismuth Subsalicylate
ADR
very FEW serious side effects
SALICYLATE concerns
STAINS –> difficult to remove
Gut Absorption Process
Normal gut absorption is dependent on the
BALANCE of:
Absorption // Secretion
of Water & Electrolytes
- *Small Intestine = 80% of fluids**
- colon absorbs the rest*
Antigrade Motility of GI Tract
SLOWER Transit –> GREATER FLUID ABSORPTION
Faster Transit –> less fluid absorption
Types of ANTIDIARRHEALS
& Goals
INCREASE water&electrolyte Absorption from the gut
by decreasing GI motility –> INCREASES transit time
Opiates
Bismuth
Gel-Forming Substances
Antimuscarinics
5-HT Antagonist
Opiates that do NOT cross the BBB
Anti-Diarrheals
- *LOPERAMIDE**
- *Imodium**
- *Diphenoxylate + Atropine**
- *Lomotil**
Loperimide & Diphenoxylate+Atropine
Opiates that do NOT cross the BBB
MoA
Increase SEGMENTAL CONTRACTIONS
of both small/large intestines
but this is NON-Synchronized –> slows down movement
in turn Increasing ABSORPTION
Decrease Secretion of FLUID & E- into lumen
CNS-Active
increase transit time & accumalation of fluid in lumen via CNS sites
Kaolin + Pectin
MoA / Drug Class
GEL-FORMING SUBSTANCE
for Diarrhea
MoA:
forms a clay-like gel when hydrated
which PROMOTES stool formation
adsorbs:
toxins / bacteria / absorbs fluid
Issue with
ANTIMUSCARINICS + OPIATES
DO NOT WANT TO PATIENTS TO TAKE A LOT OF THESE
if you SLOW down GI activity with these drugs
you run the risk of the
PATHOGEN ENTERING THE BLOOD STREAM
Antimuscarinics as Anti-diarrheals
Drugs // MoA
Dicyclomine // Propantheline // Hyoscyamine
MoA:
reduce GI MOTILITY
reduce SECRETIONS
by inhibiting parasympthetic impulses
Alosetron (Lotronex)
Drug Class / Use / MoA
5-HT3 Antagonist
for IBS w/ DIARRHEA
- *GI 5-HT Blockade**
- inhibits* unpleasant visceral sensations = Nasuea/bloating/pain
- inhibits* colonal motility –> increased transit time
- CNS 5-HT receptor inhibition*
- REDUCES* brain response to visceral afferent stimulation
Constipation
mainly an issue in
Babies & Elderly
- *SYMPTOM**
- not a disease*
Characteristics:
caused by host factors
size / frequency / consistency of bowel movements are
HIGHLY VARIABLE
often caused by dehydration of feces that stay too long in colon
Laxative
CLasses & Drugs
- *Chloride Channel Activator**
- *Lubiprostone** = Amitiza
- *Guanylate Cyclase C Agonist**
- *Linaclotide** = Linzess
Dietary fiber & bulk-forming laxatives
Psyllium (Metamucil)
Osmotic laxatives
MoM // Golytely PEG
Stimulant laxatives (Cathartics)
Bisacodyl = Dulcolax
**_Emollient laxatives (Stool softeners)_** Docusate sodium (Colace)
How do LAXATIVES promote Defacation?
RETENTION of Fluid in colonic contents
reduction in NET absorption of WATER & NaCl
INCREASED Intestinal Motility
- *Psyllium** = Metamucil
- *Methylcellulose** = Citrucel
BULK-FORMING LAXATIVES
Whole Grains // Fruits // Veggies
are similar
act as DIETARY FIBER
Bulk-Forming Laxatives
MoA // ADR
Increase in
- *Fecal MASS** // Rate of Colonic TRANSIT
- *Water Content of feces –> form Bulky / Emollient gel**
Soften feces in 1-3 days
Relief of symptoms of CHRONIC DVT
ADR:
Gas / Bloating / Ab discomfort
Osmotic & Saline Laxatives
Drugs / MoA / ADR
Magnesium Sulfate & Hydroxide
Epsom Salt // Milk of Magnesia
Osmotic Pressure –> retain water in colon
Sodium Phosphates = Fleet
stimulate secretion of cholescytokinin –> secretion & motility
ADR:
INCREASED Mg Salt absorption
Electrolyte Disturbances
PEG Electrolyte Solution
NonAbsorbable Sugars
MoA // Class / ADR
Osmotic Laxatives
- *Accumulation of Fluid** in LUMEN
- *watery evacuation
- -> 1-3 hours**
ADR:
- *Flatulence & abcramps**
- *N/V**
Stimulant Laxatives
Drugs // MoA
Bisacodyl** // **Danthron** // **Castor oil
diphenymethane // senna(anthraquinone) // ricinoleic acid
INCONSISTANT EFFECTS
act DIRECTLY to stimulate colon
–> enteric neurons & GI smooth muscle
Soft or semisolid stool in
6-8 hours
Emollient Laxatives = Stool Softeners
Drugs // MoA / ADR
Docusate Sodium** // **Lactulose
Colace
Stool softener by incorporating water –> fatty fecal matter
Surfactant = soap
Softens feces
in 1-3 days
ADR:
Nausea + AbCramp
Lubiprostone = Amitiza
CHLORIDE CHANNEL ACTIVATOR
for CHRONIC CONSTIPATION
MoA
Specifically activates Cl- Channels in gut
Increases liquid secretion –> intestines
shortens Intestinal TRANSIT TIME
Linaclotide = Linzess
GUANYLATE CYCLACE C AGONIST
used for CHRONIC Constipation
a poorly absorbed 14 AA peptide
MoA:
Binds to Guanylate Cyclace C receptor on GUT Enterocytes
activates cystic fibrosis transmembrane conductance channel
stimulates intestinal fluid secretion
