_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

27 - GI Pharmacology Flashcards by Karlo Sison

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

How well did you know this?

Not at all

Perfectly

*Prostaglandin E2 & E2**
*Function**

INHIBIT ACID

Stimulate Secretion of:
Mucus & Bicarbonate

DILATE mucosal blood vessels

How well did you know this?

Not at all

Perfectly

REDUCE INTRAGASTRIC ACIDITY

Pharmacological Mechanisms for treating PUD

Block Gastric Acid secretion
multiple mechanisms

*Neutralize Excess Gastric Acid**
*antiacids**
*Eradicate H.Pylori**
*antimicrobials**

How well did you know this?

Not at all

Perfectly

PROMOTE MUCOSAL DEFENSE
Pharmacological Mechanisms for treating PUD

*Repair Mucosal Barrier Breakdown**
*Cytoprotectants**

Prostaglandin-Stimulated Cytoprotection
Prostaglandin - analogs
ALSO reduce gastric acid secretion

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

*PPI**
*MoA**

PRODRUG
needs acidic environment –> absorbed in intestine
forms Disulfide bridge w/
H+ /K+ -ATPase Enzyme
Proton Pump
VVVVV
Decrease Gastric Acid Secretion

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

*CNS ACTIVE**
*Anti-Muscarinics**

ATROPINE

SCOPOLAMINE

CNS inactive
probantheline / methscopolamine / glycopyrolate

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

AntiMuscarinics
Scopolamine / Atropine

ADRs

Peripheral PARA-Sympatholytic Activity
Tachy Cardia // Constipation // Blurred Vision
drying/slowing

*CNS** if it crosses BBB
*sedation / memory disruption**

How well did you know this?

Not at all

Perfectly

Types of Antacids

SCAMM
Systemic –> bloodstream
•Sodium bicarbonate
•Calcium bicarbonate

non-systemic –> poorly absorbed from intestine
•Aluminum hydroxide
•Magnesium hydroxide

•Magnesium trisilicate/Aluminum trisilicate

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Non-Systemic Antacids

Mg & Al
Hydroxide

POORLY absorbed from SMALL INTESTINE
so they are NOT
likely to alter BLOOD / URINE pH

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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* ## Footnote **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) ## Footnote **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 ## Footnote ***_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** ## Footnote **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**