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Pharmacology > GI: Laxatives, Anti-Diarrheal, Gastroparesis > Flashcards

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

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2
Q

major factors causing diarrhea

A
  1. increased GI motility

2. decreased absorption of fluid

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3
Q

are anti-diarrheal agents used for acute diarrhea due to invasive organism?

A

No

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4
Q

do anti-diarrheals address underlying cause?

A

no

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5
Q

list the two anti-motility agents

A

Dipehnoxylate

Loperamide

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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

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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

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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

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9
Q

what is an adsorbent

A

solid that holds molecules of a gas or liquid or solute as a thin film

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10
Q

List the adsorbents

A

Aluminum Hydoxide

Methylcellulose (fiber)

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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*
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12
Q

most effective agent for tx of diarrheal

A

Anti-motility

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13
Q

list the agents modifying fluid and electrolyte transport

A

Bismuth Subsalicyte (Pepto)

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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
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15
Q

percent (and ml) of stool that is water

A

70-80%
or
100 mL

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16
Q

how to “calculate” water content of stool

A

fluids ingested + luminal secretion
MINUS
absoprtion in the GI tract

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17
Q

what is the first line tx for constipation

A

lifestyle modifications

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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
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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
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20
Q

chronic use of laxatives can lead to?

A

electrolyte deficiency

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21
Q

is there a risk for abuse with laxatives?

A

yes

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22
Q

how are laxatives categorized?

A

by MOA

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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)

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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
Q

List the prokinetic agents (acting primarily on?)

A

acting primarily on MOTILITY

5HT3 rec agonists

Dopamine rec antagonists

Motilides (erythromycin)

26
Q

Categories of laxatives (7)

A 
Bulk Laxatives 
Saline/osmotic Laxatives 
Lubricant Laxatives 
Stimulant Laxatives 
Stool Softeners 
Chloride channel activators (also used in IBS-C) 
Prokinetics
27
Q

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
A

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
Q

Saline Cathartics

  • list the names
  • MOA
  • OOA
  • SE
A

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
Q

Polyethylene Glycol

  • contain?
  • list the different forms
A

Contain Electrolyte Solutions

PEG–Miralax
INDS: chronic constipation

PEG + electrolytes–isotonic,
INDS: colon prep

30
Q

Indication for PEG

*se we worry about

A

chronic constipation

31
Q

Indication for PEG + electrolytes

A

colon prep

its an isotonic solution so we do not worry about electrolyte abnormalities here

32
Q

Lactulose Syrup

  • chemical makeup
  • MOA
  • INDS
  • OOA
A

*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
Q

which laxative is also usd in tx of hepatic encephalopathy

A

Lactulose

34
Q

Stimulants/irritants
MOA
list them

A

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
Q

Senna and Cascara

  • forms it comes in
  • which is not used anymore
  • active ingredient?
  • MOA
  • OOA
  • inidcation
A

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
Q

Bisacodyl (Dulcolax)

  • class
  • available forms
  • MOA
A

Stimulant/irritant
*suppositories and enteric coated tablets

MOA: potent stimulator of the colon–>acts directly on nerve fibers in the mucosa of colon

37
Q

Castor Oil

  • class
  • MOA
  • contra.. why
  • SE
A

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
Q

Docusate sodium and Docusate Calcium (Colace)

  • Class
  • MOA
  • indications
  • OOA
  • drug-drug interactions
  • SE
A

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
Q

Mineral Oil

  • class
  • MOA
  • Route of admin
A

lubricant laxative

MOA: facilitating the passage of hard stools

Route: PO–>always upright to avoid aspiration–>lipid or lipoid pneumonia

40
Q

Glycerin Suppositories

  • class
  • MOA
A

Lubricant laxatives

MOA: facilitating the passage of hard stools

41
Q

Lubriprostone (amitiza)

  • class
  • MOA
  • indication
  • OOA
  • SE
  • drug-drug interactions
A

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
Q

Linaclotide (Linzess)

  • class
  • MOA
  • indication
  • SE
  • do not use in?
A

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
Q

what are prokinetic agents?

*list the drug classes in them

A
  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
Q

Metoclopramide

  • class
  • MOA
  • indication
  • SE
  • timing of when to admin drug and DOA
A

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
Q

what is dopamine’s effect on GI tract

A

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
Q

which drug causes extrapyramidal SE

A

Metoclopramide

47
Q

Cisapride

  • class
  • MOA
  • SE
  • indication
A

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
Q

Tegaserod

  • drug class
  • indications
A

Serotonin (5HT) Receptor Agonists–prokinetic drug

*investigational new drug

49
Q

what is serotonins effect on the GI tract

A

stimulates peristalsis

50
Q

which neruotransmitter is important for normal motility and secretory actions of the gut?

A

Serotonin

51
Q

what cells release serotonin in colon

A

enterochromaffin cells

52
Q

what is motilin

A

potent hormone–contractile agent for upper GI–responsible for amplification of motility

53
Q

What mimics motilin

A

erythromycin the ABX at higher doses

54
Q

Erythromycin

  • class
  • MOA
  • inds
  • peak action
  • when to administer
  • SE
  • metabolism
A

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
Q

Dicyclomine

  • class
  • indications
  • MOA
  • SE
  • timing when to administer
A

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
Q

Hyoscyamine

  • class
  • indications
  • MOA
  • SE
  • OD s/s
  • timing when to administer
A

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
Q

what is the only approved ABX for IBS

A

Rifaximin

58
Q

Rifaximin

  • class
  • Indications
  • absorption
  • peak
  • duration of tx?
A

ABX

FDA approved for IBS-D

Well absorbed
Peak <1 hour

2 week course of treatment

Pharmacology (28 decks)

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