GI: Laxatives, Anti-Diarrheal, Gastroparesis Flashcards
1
Q
list the three classes of drugs for used to tx diarrhea
A
antimotility
adsorbents
agents modifying fluid and electrolyte transport
2
Q
major factors causing diarrhea
A
- increased GI motility
2. decreased absorption of fluid
3
Q
are anti-diarrheal agents used for acute diarrhea due to invasive organism?
A
No
4
Q
do anti-diarrheals address underlying cause?
A
no
5
Q
list the two anti-motility agents
A
Dipehnoxylate
Loperamide
6
Q
Dipehnoxylate
Loperamide
- drug class
- MOA
- OOA
- which is preferred of the two
- SE
- INDS
- Contra
- which crosses BBB and which does not
A
Anti-motility agents
MOA:
- analogs of meperidine
- opiate analogs
- have opiate actions on gut
- activate preesynaptive opioid recs in enteric NS–>inhibits ACH release and decrs peristalsis and slower GI transit time (absorb more water)
- NO analgesic affects
- rapid OOA
- Loperamide is preffered
SE:
can cause toxic megacolon–
INDS:
- acute diarrhea
- traveler’s diarrhea
- 13 YO +
CONTRA in kids and PT with colitis
Diphenoxylate crosses BBB (why it is added with atropine)
Loperamide does not cross BBB
7
Q
Loperamide
- potency?
- absorption in CNS?
- Metabolism
A
40-50X potent > morphine as an anti-diarrhea
BUT
**poor CNS penetration because cannot cross BBB
*extensive hepatic metab
8
Q
why is Dipehnoxylate added to atropine
A
since Diphenoxylate acts on opioid receptors, PT can become addicted.
-atropine + drug makes the SE of abuse noticeable and unpleasant–leading to discontinuation from the PT and decrs potential for abuse
9
Q
what is an adsorbent
A
solid that holds molecules of a gas or liquid or solute as a thin film
10
Q
List the adsorbents
A
Aluminum Hydoxide
Methylcellulose (fiber)
11
Q
Adsorbents as a class:
- MOA
- effectiveness compared to anti-motility?
- SE
A
MOA: remove toxins and intestinal organisms by binding to them–>and further protecting/coating intestinal mucosa
- NOT as effective for tx of diarrhea vs anti-motility agents
- Aluminum hydroxide– also used as an antacid and SE is constipation*
12
Q
most effective agent for tx of diarrheal
A
Anti-motility
13
Q
list the agents modifying fluid and electrolyte transport
A
Bismuth Subsalicyte (Pepto)
14
Q
Bismuth Subsalicyte (Pepto)
- MOA
- indication
- SE
A
MOA:
- decrs fluid secretion in bowel
- antimicrobial effect
- some antiinflammatory
- COATING action ANNND Salicylate action
INDS:
- travelers diarrhea
- mild diarrhea/dyspepsa
- HP—part of the quad tx
SE:
- Salicylate poisoning with overuse
- black tongue
- black stools
15
Q
percent (and ml) of stool that is water
A
70-80%
or
100 mL
16
Q
how to “calculate” water content of stool
A
fluids ingested + luminal secretion
MINUS
absoprtion in the GI tract
17
Q
what is the first line tx for constipation
A
lifestyle modifications
18
Q
list the lifestyle mods for tx of constipation (6)
A
- diet
- fiber supplements
- incr exercise
- incr water intake
- look at medication list
- predisposing dz’s that can cause constipation–EX hypothyroidism
19
Q
general MOA for laxatives (3)
A
- soften stool (retaining fluid in stool)
- accelerate motility of bowel (propulsions)
- decreasing absorption of fluid by altering electrolyte transport
20
Q
chronic use of laxatives can lead to?
A
electrolyte deficiency
21
Q
is there a risk for abuse with laxatives?
A
yes
22
Q
how are laxatives categorized?
A
by MOA
23
Q
List the luminally active agents (classes)
A
Hydrophillic colloids, bulk forming agents (fiber)
Osmotic agents (nonabsorbable salts/sugars)
Stool-wetting agents (surfactants) and emollients (docusate, mineral oil)
24
Q
list the nonspecific stimulants or irritants
*do these have effect on fluid secretion and motility?
A
Diphenylmethanes (biscodyl)
Anthraquinones (senna and cascara)
Castor Oil
YES effect on fluid secretion and motility
25
List the prokinetic agents (acting primarily on?)
acting primarily on MOTILITY
5HT3 rec agonists
Dopamine rec antagonists
Motilides (erythromycin)
26
Categories of laxatives (7)
```
Bulk Laxatives
Saline/osmotic Laxatives
Lubricant Laxatives
Stimulant Laxatives
Stool Softeners
Chloride channel activators (also used in IBS-C)
Prokinetics
```
27
Fiber
* list the agents / class
* what are they chemically
* MOA
* OOA
* SE
* caution with what PT
* which one can interact with other drug's absoprtion
BULK LAXATIVES
Bran, Psyllium, Methylcellulose
*natural or synthetic polysaccs--NOT digestible
MOA: since they not digestible-->get to colon-->bacteria ferment it-->creates FAs that are prokinetic-->bacterial mass increases-->creates a GEL in the LI-->water retention-->intestinal distention-->increasing peristalsis
OOA: 12-72 hours
SE: Bloating
Caution in IMMOBILE Pts beacuse can cause severe bloating and/or obstruction
Psyllium can reduce the absoprtion of other PO drugs--so separate the adminstration of the two+ agents by TWO hours
28
Saline Cathartics
* list the names
* MOA
* OOA
* SE
Mag Citrate and Mag Hydroxide
MOA: non-absorbable salts aka anions and cations-->increase H20c(water follows salt)-->distends bowel-->increases motility
****holds water in intestines thru osmosis
OOA: few hours
SE:
****be aware of hypermag
29
Polyethylene Glycol
* contain?
* list the different forms
Contain Electrolyte Solutions
PEG--Miralax
INDS: chronic constipation
PEG + electrolytes--isotonic,
INDS: colon prep
30
Indication for PEG
| *se we worry about
chronic constipation
31
Indication for PEG + electrolytes
colon prep
| its an isotonic solution so we do not worry about electrolyte abnormalities here
32
Lactulose Syrup
* chemical makeup
* MOA
* INDS
* OOA
*semisynthetic disaccharide sugar
MOA:
* acts as osmotic laxative
* degraded by bacteria into short chain FAs (lactic, formic and acetic acids)--incrs osmotic pressure-->causing fluid accumulation-->colon distention-->soft stools-->defecation (create propulsion)
OOA: 24-48 hours
INDS:
* opioid induced constipation
* elderly constipation
* idiopathic constipation
* hepatic encephalopathy bc it can reduce ammonia levels
33
which laxative is also usd in tx of hepatic encephalopathy
Lactulose
34
Stimulants/irritants
MOA
list them
MOA:
* directly effect enterocytes, enteric neurons and GI SM
* can induce limited low-grade inflammation in small and lrg bowel-->accumulation water + electrolytes
Senna and Cascara
Bisacodyl (Dulcolax)
Castor Oil
35
Senna and Cascara
* forms it comes in
* which is not used anymore
* active ingredient?
* MOA
* OOA
* inidcation
STIMULANT /IRRITANT
liquid, tablet
CASCARA not used anymore
*active ingredient: sennosides
MOA:
*water + electrolyte secretion into the bowel-->stimulate bowel motility
OOA: 6-12 hours when taken PO
IND:
*when combined with docusate good for opioid induced constipation
36
Bisacodyl (Dulcolax)
* class
* available forms
* MOA
Stimulant/irritant
*suppositories and enteric coated tablets
MOA: potent stimulator of the colon-->acts directly on nerve fibers in the mucosa of colon
37
Castor Oil
* class
* MOA
* contra.. why
* SE
stimulant/irritant
MOA: broken down (in SI) into Ricinoleic acid-->very irritating on stomach-->quickly induces peristalsis.
CONTR: pregnant women because it can induce uterine contractions
SE:
*GI adverse effects
38
Docusate sodium and Docusate Calcium (Colace)
* Class
* MOA
* indications
* OOA
* drug-drug interactions
* SE
Stool Softener aka Emollient Laxative
MOA:
* lowers surface tension of stool-->allows mixing of FAs (emulsification) + watery substances-->softens stool-->easily evacuated if softened
* stimulates intestinal fluid and electrolyte secretion-->later stimulating intestinal mucosal permeability
Indication:
*prophylaxis and not so much acute tx
OOA: Days
Drug-drug:
*do not take with mineral oil bc of potential of mineral oil to absorb
SE:
*generally well tolerated
39
Mineral Oil
* class
* MOA
* Route of admin
lubricant laxative
MOA: facilitating the passage of hard stools
Route: PO-->always upright to avoid aspiration-->lipid or lipoid pneumonia
40
Glycerin Suppositories
* class
* MOA
Lubricant laxatives
MOA: facilitating the passage of hard stools
41
Lubriprostone (amitiza)
* class
* MOA
* indication
* OOA
* SE
* drug-drug interactions
Secretory Agent (chloride chanel activator)
MOA: activates Cl- channels-->increases fluid secretion in the intestinal lumen-->eases passage of stool with LITTLE electrolyte change
*increases weekly BMs
IND:
* IBS-C
* chronic constipation
OOA: 24 hours
SE:
* N/V
* dyspepsia
* HA
* dizziness
* hypotension
*Very little drug-drug interactions bc drug is quickly absorbed in stomach + jejunum
42
Linaclotide (Linzess)
* class
* MOA
* indication
* SE
* do not use in?
Secretory Agent
MOA:
peptide agonist of cyclic GMP-->enhancing Cl- and HCO3- secretion into the lumen-->incrs water secretion-->increasing motility
IND:
*IBS-C
```
SE:
*diarrhea
*abdmon pain
*flatulence
*HA
*abdominal distention
DO NOT USE in PT <17 YO
```
43
what are prokinetic agents?
| *list the drug classes in them
1. medications that enhance the GI motility and transit of GI tract contents by enhancing excitatory NTs w.o interfering with normal pattern
* Dopamine Receptor Antagonists
* Serotonin Receptor Agonists
* Motilin and Macrolide Antibiotics
44
Metoclopramide
* class
* MOA
* indication
* SE
* timing of when to admin drug and DOA
Class: dopamine Rec antagonists
MOA:
1. agonism to serotonin (5Ht4) rec
2. vagal and central 5Ht3 antagonism
3. possible sensitization on muscarinic recs on smooth muscle
4. dopamine antagonism
all of this results in coordinated muscle contraction
INDS:
* anti-emetic and anti nausea (2nd or 3rd line)
* Gastroparesis (main use of this drug)
SE:
*Extrapyramidal SE --dystonia, dyskinesia
*admin 30 min before effect is desired (EX: before chemo or before meals)
DOA: 1-2 hours
45
what is dopamine's effect on GI tract
inhibitory effect on the GI motility since D2 receptors mediate suppression of ACH release from myenteric motor neurons
**so the dopamine ANTAGONISTS stimulate this normal effect--- creating a PROKINETIC effect on GI tract
46
which drug causes extrapyramidal SE
Metoclopramide
47
Cisapride
* class
* MOA
* SE
* indication
Serotonin (5HT) Receptor Agonists--prokinetic drug
MOA
>90% of serotonin receptors are in the gut-- serotonin stimulates peristalsis
SE:
* FATAL cardiac arrythmias--VT, torsades
* use is limited now
IND:
*nighttime GERD
48
Tegaserod
* drug class
* indications
Serotonin (5HT) Receptor Agonists--prokinetic drug
*investigational new drug
49
what is serotonins effect on the GI tract
stimulates peristalsis
50
which neruotransmitter is important for normal motility and secretory actions of the gut?
Serotonin
51
what cells release serotonin in colon
enterochromaffin cells
52
what is motilin
potent hormone--contractile agent for upper GI--responsible for amplification of motility
53
What mimics motilin
erythromycin the ABX at higher doses
54
Erythromycin
* class
* MOA
* inds
* peak action
* when to administer
* SE
* metabolism
Macrolide- prokinetic agent
MOA:
1. mimicks the effects of motilin
2. increases LES pressure
3. stimulates gastric and Sm bowel contractility
4. little/no effect on colonic motility
IND:
* diabetic gastroparesis (more so upper GI issues like esophagus and small bowel)
* refractory GERD (not first line) due to increasing LES pressure
Peak action: 30 mins to 2.5 hrs
administer 30 mins b4 meals
metabolized liver by CYP34A--always check drug-drug interactions
SE:
* GI toxicity
* Ototoxicity
* Pseudomembranous colitis
* QT prolongation
* sudden death
55
Dicyclomine
* class
* indications
* MOA
* SE
* timing when to administer
Antispasmodics/Anticholinergic agents
Indications: IBS-C and IBS-D
MOA: antimuscarininc--decrs GI spasms and motility
SE: anticholinergic effects like drowsiness and dry mouth
*given PRN or before meals to prevent pain and fecal urgency
56
Hyoscyamine
* class
* indications
* MOA
* SE
* OD s/s
* timing when to administer
Antispasmodics/Anticholinergic agents
INDS: IBS-C and IBS-D
MOA: antimuscarininc--decrs GI spasms and motility
SE: drowsniess, dry mouth
OD: hallucinations, arrhythmias, N/V
*given PRN or before meals to prevent pain and fecal urgency
57
what is the only approved ABX for IBS
Rifaximin
58
Rifaximin
* class
* Indications
* absorption
* peak
* duration of tx?
ABX
FDA approved for IBS-D
Well absorbed
Peak <1 hour
2 week course of treatment
