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Pharmacology > Motility, Laxatives, Anti-diarrheals, IBD > Flashcards

Motility, Laxatives, Anti-diarrheals, IBD Flashcards

1
Q

Which classes of drugs stimulate motility?

A
  1. Metocloparamide
  2. Cholinergic or Acetylcholinesterase
  3. Macrolides
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2
Q

Bethanecol, Neostigmine, are in what drug class?

A
  1. Cholinergic or Acetylcholinesterase
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3
Q

What is MOA of bethanecol

A

stimulates muscarinic receptors on muscle cells and my-enteric plexus
*used to tx gastroparesis

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4
Q

What is MOA of neostigmine?

A

blocks AChE to prolong affect of Ach

* enhances gastric and colonic emptying

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5
Q

What are the ADE of cholinergic agents?

A
  • salivation
  • N/V/D
  • bradycardia
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6
Q

What are the clinical uses of cholinergic agents?

A
  • GERD
  • diabetic gastroparesis
  • post surgical disorders that cause delayed emptying ( vagotomy, antrectomy
  • to promote advancement of nasoenetric tubes from stomach to duodenum
  • non-ulcer dyspepsia
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7
Q

What is MOA of metoclopramide?

A

Dopamine receptor antagonist

  • blocks cholinergic smooth muscle stimulation
  • Increases: esophageal peristalsis, gastric emptying, LES pressure
  • has NO effect in small intestine or colon
  • anti-emetic action: blocks chemo receptor zone in medulla
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8
Q

What are ADE of metoclopramide?

A
  • CNS: insomnia, agitation, drowsiness
  • Extra pyramidal effects: Parkinsonism, dystonias, akathisia
  • Tardive dyskinesia
  • elevated prolactin (galactorrhea, gynecomastia, impotence , menstrual disorders
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9
Q

What is MOA of macrolides/ azithromycin?

A

-binds motilin receptors on gastrointestinal smooth muscle and produce onset of migrating motor complex

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10
Q

What is a disadvantage to using macrolides?

A

-rapid tolerance develops

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11
Q

What is the clinical use of macrolides?

A
  • tx for gastroparesis

- used when patient has upper GI bleed and need to promote gastric emptying of blood for endoscopy

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12
Q 
What drug class do the follwoing belong to:
Bulk forming
Stool softeners
osmotic laxatives
stimulant laxatives
chloride channel activator 
Guanylate-cyclase C agonists
Opioid receptor antagonist 
Seratonin 5HT4 receptor agonist
A

Laxatives

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13
Q

Which drug classes can cause constipation?

A
  • Opioids
  • Diuretics
  • Calcium carbonate or or AlOH antacids
  • Iron preparations
  • NSAIDS
  • TCA
  • Anti-cholinergic
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14
Q

How do you prevent constipation?

A
  • high fiber diet
  • adequate fluid intake
  • exercise
  • heeding of nature’s call
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15
Q

How do you treat constipation?

A

-treat the specific diagnosis
or
choose symptomatic therapy
Ex. give opioid antagonist to tx opioid induced constipation

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16
Q

Which agents cause watery evacuation of stool in 1-6 hrs?

A

PEG-4L
Magnesium citrate or Magnesium hydroxide
Bisacodyl -rectal prep
sodium phosphate

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17
Q

Which agents cause semi fluid stools in 6-12 hrs?

A

Bisacodyl- 15mg orally

Senna

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18
Q

Which bulking agents cause fecal softening in 1-3 days?

A

Psyllium
Polycarbophil
Methylcellulose4-6 gm/day

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19
Q

What is MOA of bulk forming laxatives?

A

they are indigestible colloids that attract water creating bulk and dilating the colon ( emollient gel created)=peristaltic waves

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20
Q

What are common preparations of bulk forming agents?

A
  • Natural: psyllium, methylcellulose

synthetic: polycarbophil

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21
Q

What are ADE of laxatives?

A

bloating and flatulence

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22
Q

What is clinical use of bulking laxatives?

A
  • used for prevention of constipation

- don’t use in mega colon or mega rectum

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23
Q

What is MOA of stool softeners?

A

-decrease surface tension of stool allowing water to penetrate and soften the stool main passage easier

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24
Q

Name two stool softeners?

A
  • docusate (rectal or oral administration

- mineral oil ( lubricates fecal material, not tasty but take with juice?

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25
Q

What is the clinical use of stool softeners?

A
  • tx fecal impaction in kids and adults
  • prevent constipation
  • reduce straining at defecation
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26
Q

What are the disadvantages of stool softeners?

A
  • long term use can cause deficiency in fat soluble ADEK vitamins
  • aspiration can lead to lipid pneumonitis
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27
Q

What is MOA of osmotic laxatives?

A

-work in the colon by retaining water in the lumen ( create an osmotic pressure)
side note: the colon is isotonic and cannot concentrate or dilute

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28
Q

Lactulose and Sorbitol -nonabsorbable sugar laxatives

Milk of Mg (MgOH)

A

ADE of Lactulose/Sorbitol: flatulence

ADE of milk of mg: dont use if pt has renal issues

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29
Q

What is clinical use of Sugar/Salt osmotic laxatives?

A

acute constipation or prevention of chronic constipation

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30
Q

Which osmotic laxative is considered a purgative?

A

Mg citrate or Sodium phosphate

-prompt bowel evacuation in 1-3 hrs

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31
Q

What are some concerns with sodium phosphate?

A
  • high phosphate
  • low calcium
  • high soidum
  • low K
  • all of these can casue heart issues
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32
Q

What is the clinical use of PEG?

A
  • clean colon before endoscopy

- prevention tx in chronic constipation

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33
Q

What is special about PEG?

A

-it is safe for everyone to use because it is an isotonic soln that has an inert, non-absorbable , osmotically active sugar (PEG) and is designed so that no shift in electrolyte fluids occur

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34
Q

What are ADE of PEG

A

safe!

does not cause cramps or flatus!

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35
Q

What is MOA of stimulant?

A

-directly stimulate the enteric NS

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36
Q

What is clinical use of stimulant?

A

long term use for bed bound patients

neurologically impaired

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37
Q

T/F Nerve damage may be the cause of chronic constipation rather than the use of stimulant laxatives

A

True

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38
Q

Aloe, senna, and cascara are what drug class?

A

stimulant laxative -athraquinone derivatives

occur naturally in plants

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39
Q

What is MOA of stimulant laxative -athraquinone derivatives?

A

hydrolyzed in the colon and produce bowel movement in 6-12 hrs when oral 2 hrs when given rectally

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40
Q

What is special about Aloe, senna, and cascara?

A
  • chronic use can cause brown pigmentation of colon “melanosis coli”
  • concern that these agents are carcinogenic but epidemiology studies don’t support that
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41
Q

What is bisacodyl?

A

stimulant laxative-dimethylphenate derivative class

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42
Q

What is clinical use fo bisacodyl?

A

tx for acute and chronic constipation

  • oral dose: 6-10 hrs for bowel movement to happen
  • rectal dose: 30-60 min for passage to occur
  • used with PEG for colon cleanse before endoscopy
43
Q

What are ADE of bisacodyl?

A

safe for long term use

minimal systemic absorption: overall safe

44
Q

Naloxegol, Alvimopan, methylnaltrexzone are what drug class?

A

Opioid receptor antagonist

45
Q

What is MOA of Opioid receptor antagonist?

A

act peripherally to block opioid receptors and dont affect analgesia in CNS
-don’t cross blood brain barrier

46
Q

What is clinical use of methylnaltrexozone?Alvimopan?Naloxegol?

A
  • tx for opioid induced constipation in palliative care
  • tx for post-operative ileus in hospitalized patients who have undergone large bowel resection, no more than 7 days, CVD risk
  • tx for opioid induced constipation, contraindicated in pts with obstruction
47
Q

Which drugs can cause diarrhea?

A
  • ABx: clindamycin
  • Methyldopa
  • Digoxin
  • PPI
  • H2 blockers
48
Q

How do you treat acute diarrhea?

A

<3 days and fever and neg stool sample: abx and
< 3 days and fever with + stool sample for ova, parasite: tx disease
< 3 days and no fever: give fluids, loperamide, diet modification

49
Q

How do you tx chronic diarrhea?

A

> 14 days–> get H&P–>infection, IBD, drug induced,
motility issue–>dx: stool sample, endoscopy, culture–>TX : depends on cause if no identified casue give fluids, loperamide, adjust diet

50
Q

T/F It is not appropriate to withhold foods in patients with no dehydration and diarrhea

A

TRue

51
Q

T/F As bowel movements decrease a band diet is begun

A

True

BRAT diet

52
Q

T/F Anti-diarrhea agents are not used in bloody diarrhea or systemic toxcity

A

TRUE

53
Q

What is an anti-motility diarrhea drug?

A

Opioid agonist

-constipating effect

54
Q

What is an adsorbent anti-diarrheal drug?

A

Kaolin-pectin

55
Q

What is an anti-secretory anti-diarrheal?

A

Colloidal bismuth
Bile salt binding resins
Octreotide
Bacterial replacement and enzymes

56
Q

What is MOA of opioid agonists?

A
  • inhibit presynaptic cholinergic neurons in myenteric plexus
  • increased colonic transmit time and fecal wtaer absorption
57
Q

What is lopermaide?Diphenoxylate?

A
  • opioid agonist-OTC
  • does not cross blood brain barrier
  • no analgesia
  • prescription opioid agonist
  • with higher doses have CNS effects
  • can lead to opioid dependence
58
Q

What is MOA of Kaolin-pectin?

A

adsorbs nutrients, toxins and digestive juices onto the surface of the product

59
Q

What is MOA bile acid sequestrants?

A

-bile acids are not absorbed in ileum can cause diarrhea in certain disorders?
BAS act by binding the bile

60
Q

Cholestyramine, Colestipol, Colesevelam are what drug class?

A

Bile acid sequestrants

61
Q

What are ADE BAS?

A
  • fecal impaction
  • constipation
  • bloating
  • fat malabsorption
  • bind other drugs and reduce theri absorption (Except colesevelam)
62
Q

What is an anti-secretory anti-diarrheal?

A

Octreotide

63
Q

What is somatostatin?

A
  • 14 a.a peptide released in GI tract from D cells, paracrine cells, hypothalamus, enteric nerves
  • inhibits hormone secretion:
  • reduces intestinal and pancreatic fluid secretion
  • slows GI motility and gall bladder contraction
64
Q

What is 1/2 life of somatostatin?

A

3 min when given by IV-limits is usefulness

65
Q

What is the clinical use of octreotide?

A

blocks the effects of endocrine tumors
other uses: stops pancreatic secretion in patients with a panc fistula, tx for acromegaly ( pituitary tumors), decreases splanchinic blood flow ( GI bleed)

66
Q

Which cancers cause secretory diarrhea?

A

VIPoma

carcinoid

67
Q

What are ADE of octreotide?

A
  • steatorrhea
  • bradycardia
  • hypothyroidism
  • N/V/D, flatulence
68
Q

TX for bacterial agent causing diarrhea

A 
C. jejuni: Cipro or Azithro
Cholera: Cipro or Azithro, or Doxy
C. diff: oral vancoycin or metronidazole 
Shigella: Cipro, Azithro
Giardia: Metronidazole 
E. hystolitca: Metro, Tinidazole
69
Q

What are the three types of IBS?

A

IBS-D
IBS-C
IBS-M

70
Q

What is 1st ine tx for IBS-C?

A

1st: Psyllium
2nd line: PEG
3rd line: Lubiprostone, linaclotide, plecanatide
Refractory: tegaserod , prucalopride

71
Q

T/F For IBS-C PEG improves constipation but not abdominal pain?

A

TRUE

72
Q

What is MOA of Lubiprostone?

A
  • stimulates type II chloride channel in small intestine and draws chloride rich fluid into the lumen
  • stimulates intestinal motility
73
Q

What is the clinical use of lubiprostone?

A

used for IBS-C in women >18 y/o

unproven efficacy in men

74
Q

ADE of lupbiprostone?

A
  • reduce the dose in hepatic issues
  • Nasuea
  • Pregnancy C category-don’t use in women of child bearing age
75
Q

What is MOA of Linaclotide?

A

Guanylate Cyclase C Agonist - stimulates intestinal fluid secretion and reduces transit time

76
Q

When do you prescribe linaclotide?

A

used in patients who have constipation despite being on PEG tx
-significant improvement in abdominal pain

77
Q

What is ADE of Linaclotide?

A

Diarrhea

78
Q

What is MOA of Plecanatide?

A

Guanylate Cyclase -C agonist : increase in cGMP luminal intestinal epithelium which increase bicarbonate and Chloride and increases GI transit time

79
Q

What is the clinical use of Plecanatide?

A

chronic constipation IBS-C

80
Q

What is black box warning for Plecanatide?

A

dehydration risk in pediatric patients

-don’t use in pregnancy

81
Q

What are ADE of plecanatide?

A

UTI
Sinusitis
Increased AST/ALT

82
Q

What is MOA of tegaserod?

A

5-HT4 receptor agonist

-stimulates peristaltic reflex and intestinal secretion

83
Q

What is the clinical use of tegaserod?

A

only used in emergency situations for IBS-C or chronic idiopathic constipation in women <55

84
Q

What are ADE of tegaserod?

A

increased # of cardiovascular deaths

85
Q

What is MOA of Prucalopride?

A

selective high affinity 5HT4 receptor agonist
-promotes cholinergic and non adrenergic neurotransmission by enteric neurons leading to peristaltic reflex , intestinal secretions and GI motility

86
Q

T/F Reduce dose of Prucalopride in patients with renal issues

A

True

87
Q

What are ADE of prucalopride?

A

N/V/D

HA

88
Q

What is 1st tx for IBS-D?

A

1st: loperamide

give 2mg 45 min before each meal, on regularly scheduled doses

89
Q

How does loperamide work?

A
  • inhibits peristalsis, prolongs transit time,

- it does NOT improve bloating or abdominal pain

90
Q

What is Eulaxodine?

A

-it is mu and kappa receptor agonist and kappa receptor antagonist

91
Q

What is MOA of Eluxadoline?

A

-acts locally to reduce abdominal pain and diarrhea
doe not cause constipating effects!!
-A mixed mu-opioid receptor agonist, delta-opioid receptor antagonist and kappa opioid receptor agonist

92
Q

What is the clinical use for Eluxadoline?

A

IBS-D

93
Q

What is contraindications for use Eluxadoline? (4)

A

biliary disorders
liver failure
pancreatitis
alcohol use

94
Q

What are ADE of Eluxadoline?

A 
nausea 
constipation
pancreatitis 
CNS depression
abuse potential
95
Q

What is 2nd line tx for IBS-D?

A

Bile acid sequestrants
Cholestyramine, Colestipol, Colesevelam
-50% of patients with IBS-D have bile acid malabsorption

96
Q

What are ADE of bile acid sequestrants?

A

bloating, flatulence, abdominal pain, constipation

97
Q

What is MOA for Alosetron?

A

5HT3 receptor antagonist
block activation of visceral afferent pain sensation from enteric NS to spinal cord and reduce sensation of nausea, bloating, and pain
-blockade at the terminal ends of entric neurons also decreases motility in left colon and increases total colonic time

98
Q

What is the clinical use of Alosetron?

A

IBS-D in women who have failed all other therapies

efficacy in men not established

99
Q

PK of alosetron?

A

potent 5HT3 antagonist-long duration of action
extensive cytochrome P450 metabolism
-rapidly absorbed in GI- 50% bioavailability

100
Q

What is efficacy of alosetron?

A
  • reduces lower abdominal pain, cramps, urgency and diarrhea
  • reduces # of bowel movements and improves stool consistency
101
Q

What is black box warning for Alosetron?

A

GI toxictity
ADE: constipation, ischemic colitis requires FDA approval
No know drug interactions

102
Q

What is additional therapy that can help tx chronic abdominal pain in IBS?

A

TCA: low dose amitriptyline or desipramine

  • alters CNS processing of visceral afferent info
  • reduces stool liquidity and frequency
103
Q

What is the role of antispasmodics in IBS?

A
  • dicylcomine and hyoscyamine
  • work through anti-cholinergic activities dry mouth, - -higher doses can cause visual disturbances, urinary retention, constipation

Pharmacology (47 decks)

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