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Year 1: Patho/Pharm > GI PHARM 2 > Flashcards

GI PHARM 2 Flashcards

1
Q

Define
Laxative effect

A

Produce soft, formed stool in 1 or more days

  • slower onset
  • mild effect
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2
Q

Define
Catharsis

A

Prompt fluid evacuation from rectum

  • fast onset
  • intense
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3
Q

Function of the colon

A

Absorb water and electrolytes

  • 1500mL enters the colon
  • 90% water is reabsorbed

*minimal nutrient absorption

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4
Q

Function of the colon is defined by…

A

Consistency of stool (versus stool frequency)

Soft formed stool
Minimal straining

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5
Q

Rome IV Criteria for Constipation
ADULTS

A

2 or more of the following for past 3 months, 25% of the time

  • straining
  • lumpy hard stool
  • incomplete evacuation
  • anorectal blockage
  • manual manuever required (digital, pelvic floor)
  • </= 3 BM per week
  • rarely loose and not IBS
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6
Q

Rome IV Criteria for constipation
CHILDREN

A

1 month with at least 2 criteria
Children </= 4 years

  • </= 2 BM per week
  • stool retention
  • painful hard stool
  • large diameter stool
  • 1x per week incontinence
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7
Q

Indication
Laxatives

A
  • reduce painful elimination (hemorrhoids, anal fissures, episiotomy)
  • Anthelmintic: obtain fresh stool sample (parasites); empty bowel before parasite treatment; empty colon of dead parasites
  • Empty bowel before surgery
  • Modify ileostomy/colostomy effluent
  • prevent fecal impaction bedrest
  • correct constipation (pregnancy, opioid use)
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8
Q

Non pharmacological interventions
Constipation

A
  • increase fluid
  • increase fibre
  • walk after meals
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9
Q

Laxatives
Infants pregnancy

A

Infants
- glycerin, ducosate, lactuluose

Children
- bisacodyl, mineral oil, Senna, ducosate, MgOH

Pregnancy
- caution
- can cause pre-term labour

Breastfeeding
- Senna

Older adults
- caution
- dehydration
- everything is safe

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10
Q

Laxative classification
MOA

A
  1. Bulk forming
  2. Surfactant
  3. Stimulant
  4. Osmotic agent
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11
Q

Bulk forming laxative
Example

A
  1. methylcellulose
  2. Psyllium
  3. Polycarbophil
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12
Q

Surfactant Laxative
Example

A
  1. ducosate sodium
  2. ducosate calcium
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13
Q

Stimulant laxative
examples

A
  1. Bisacodyl
  2. Senna
  3. Caster oil

*cannot be used in infants

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14
Q

Osmotic Laxative
Examples

A
  1. polyethylene glycol
  2. lactulose
  3. magnesium hydroxide, magnesium citrate, magnesium sulfate
  4. Sodium phosphate
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15
Q

Classification Laxatives
Therapeutic action

A

Group I: watery stool in 2-6 hours (bowel prep)

Group II: intermediate semi-fluid stool in 6-12 hours

Group III: slow 1-3 days, soft formed stool (chronic constipation relief)

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16
Q

Example Group I Laxatives

A

*liquid stool, 2-6 hours

High dose osmotic laxative
- Magnesium salts
- Sodium salts
- Polyethylene glycol
- Caster oil

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17
Q

Example Group II Laxatives

A

*semi-fluid stool 6-12 hours

Low dose osmotic laxative
- Magnesium salts
- sodium salts
- polyethylene glycol

Stimulant laxatives
- bisacodyl (oral)
- Senna

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18
Q

Example Group III Laxatives

A

*soft stool, 1-3 days

Bulk forming laxatives
- Methylcellulose
- Psyllium
- POlycarbophil

Surfactant laxative
- decosate sodium
- decosate calcium

Osmotic laxative
- lactulose

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19
Q

MOA
Bulk forming laxatives

A

Increase stool bulk, form viscous gel in water, increase stretch of GI, and peristalsis

Hasten transit time of stool through GI

*nutrients for GI bacteria

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20
Q

AE
Bulk forming laxatives

A

Non-digestable
Non-absorbable
*minimal systemic effects

Esophageal obstrution
GI
Patient education: take with water

obstruciton/impaction

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21
Q

Contraindications
Bulk forming laxatives

A

Narrowed GI

Dysphagia

Can cause GI obstruction and impaction

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22
Q

Indications
Bulk forming laxatives

A

Soft, formed stool, 1-3 days

Constipation

Diverticulitis

Relief of diarrhea (IBS)

colostomy/ileostomy bags

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23
Q

Surfactant Laxatives
MOA

A
  1. Lower surface tension allowing water to easily penetrate feces
  2. Prevent GI from absorbing water, Promote GI to secrete water and electrolytes into lumen
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24
Q

Indication
Surfactant laxatives

A

Group III laxative
soft BM in 1-3 days

Full glass of water

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25
Q

Stimulant Laxatives
MOA

A
  1. Stimulate GI motility
  2. increase water and electrolyte secretion into lumen (and reduce absorption)

Group II
Semi-fluid stool in 6-12 hours

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26
Q

SE & Contraindications
Bisacodyl

A

Contraindications
- do not crush the pill (gastritis)
- do not administer with milk (wait 1 hour)
- not safe in infants

SE
- proctitis

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27
Q

SE & Contraindications
Senna

A

Contraindications
- not safe in infants

SE
- yellow, brown or pink urine

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28
Q

Caster oil
MOA

A

Stimulant laxative
Group I: liquid stool in 2-6 hours

Acts on the small intestine, rapid evacuation

Intestinal lipase converts to ricinoleic acid 1. surfactant 2. stimulate motility 3. increase secretion water, electrolytes into GI (prevent absorption)

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29
Q

MOA
Osmotic laxatives

A

High dose laxative salts are poorly absorbed

Draw water into lumen, fecal swelling, stimulation peristalsis with GI wall stretch

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30
Q

Dosage and MOA
Osmotic laxative salts

A

Low dose
Group II
semi-fluid stool 6-12 hours

High dose
Group I
Fluid stool 2-6 hours

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31
Q

AE
Osmotic Laxative Salts

A

Magnesium toxicity

Sodium stimulated fluid volume overload: HF, HTN, edema

Kidney failure, HTN, Heart failure, Edema

Dehydration

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32
Q

Contraindications
Osmotic Laxative salts

A

Dehydration

Kidney failure

Heart failure

HTN

Edema

ACE inhibitors, diuretics, ARBs –> dehydration –> Kidney failure

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33
Q

SE
Polyethylene glycol

A

not absorbed systemically

Nausea
abdominal bloating
cramping
flatulence
diarrhea at high dose

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34
Q

Indication
PEG

A

osmotic laxative
chronic constipation
17g daily in 4-8oz of water

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35
Q

Lactulose
MOA

A

Group III: Osmotic laxative

disaccharide of galactose and fructose
*not absorbed or digested by GI enzymes

Digested by colon bacteria

Conversion to lactic acid, formic acid, acetic acid

pull water into intestine, soft, formed stool, 1-3 days

excrete ammonia

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36
Q

Lactulose
Indications

A

Group III: osmotic laxative, soft stool, 1-3 days

Chronic liver disease: hepatic encephalopathy, excretion ammonia

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37
Q

Contraindiciations
Laxatives

A
  • appendicitis
  • enteritis
  • c diff
  • diverticulitis
  • ulcerative colitis, Crohn’s disease
  • acute abdominal surgery
  • fecal impaction
  • bowel obstruction
  • caution pregnancy
  • magnesium and sodium salts: kidney disease, heart disease
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38
Q

Patient instructions
Laxatives

A

lowest dose, shortest duration

can diminish deification reflex

drink water

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39
Q

Laxative abuse
Cycle

A

Laxative clears bowel
takes 2-5 days for another BM
*think constipated and repeat the dosage

40
Q

Diarrhea
Definition

A

Increase
1. volume
2. frequency
3. fluidity
of stool

41
Q

Diarrhea
Causes

A
  1. infectious
  2. malabsorption
  3. Inflammation
  4. Bowel disorders (IBS, IBD)
  5. Drugs
42
Q

Management of Diarrhea

A
  1. diagnose cause (infectious, malabsorption, inflammation, disorder)
  2. Treat cause
  3. reverse dehydration, electrolyte imbalances
  4. reduce passage of stools
  5. reduce cramping
43
Q

Two types of anti-diarrheal drugs

A
  1. Specific
    - treat the cause
  2. Non-specific
    - treat the frequency of passage of stools
    - Ex. opioids
44
Q

Opioid Anti-Diarrheal
Examples

A
  • Diphenoxylate (lomotil)
  • Loperamide (Imodium)
45
Q

Opioid anti-diarrheal
MOA

A
  1. Bind mu receptors in GI tract, slow motility, increase Sphincter tone, decrease secretions, increase absorption water, electrolytes, decrease stool volume and frequency
  2. Promote absorption water and electrolytes in small intestine (prevent excretion water, electrolytes)
46
Q

SE
Opioid anti-diarrheals

A
  1. Toxic megacolon IBD
  2. High dose = morphine like effects
  3. Prevent passage of infection (increase duration disease)

High doses diphenoxylate
Equate to morphine

CNS supression
Respiratory suppression
constipation
urinary retention
Euphoria
hypotension, bradycardia

*Atropine included in diphenoxylate (lomotil) to prevent abuse

47
Q

Why is loperamide not regulated

A

It is too large to cross the BBB

48
Q

Management of Infectious Diarrhea

A

Majority self limiting - resolve in 24 hours

Anti-diarrheals prolong disease

Infections requiring antibiotics:

  • Salmonella (gram negative)
  • Shiegella (gram negative)
  • Campylobacter (gram negative)
  • Clostridium dificile (+ anaerobe)
  • sometimes E. coli
49
Q

Traveller’s Diarrhea
Etiology

A

E. coli (gram negative bacilli)
Most common

Usually self limiting
- drinking water
- eating local unwashed food
- do not take anti-diarrheal if moderate or severe

50
Q

Prevention Traveller’s Diarrhea

A
  • boil, cook, peel or forget it
  • avoid raw, uncooked meat, fish, seafood, dairy
  • don’t drink tap water, ice cubes
  • ground grown greens, vegetables, fruits (untreated water)
  • street vendors unless hot
51
Q

Anti-biotic treatment in Thailand, India, Nepal, Indonesia

A

Azithromycin

*resistance to fluroquinolones is high

52
Q

Definition and Treatment
Mild to Moderate
Traveller’s Diarrhea

A

E. coli.

up to 3 BM per day
No blood
No fever

First line
Loperamide (opioid)
Bismuth subsalicylate (antibiotic)

Should resolve 24 hours

53
Q

Definition and Treatment
Moderate to Severe
Traveller’s Diarrhea

A

Moderate
3-5 BM per day
no blood or fever

Severe
3-5 BM per day
blood and/or fever

First line
Fluroquinolones: norfloxacin, ciprofloxacin, levofloxacin

Second line
Azithromycin (first line children, pregnant)
Rifaximin (no blood, not pregnant)

54
Q

Indications
Prophylaxis treatment
Traveller’s Diarrhea

A

Anti-biotics:
start day 1 high risk area
continue 1-2 days upon return home
maximum: 3 weeks

Probiotics
- lactobacillus
- Saccharomyces

Vaccination (Dukoral)
- high risk, short term travel
- children > 2 years
- chronic illness
- greater risk (hypochlorhydria, immunocompromised, history repeat travellers diarrhea)

55
Q

Non pharmacological treatments
Traveller’s Diarrhea

A

Fluid
- clear fluid
- salted crackers
- electrolyte solutions
- pedialyte (children)

56
Q

Contraindications
Moderate to Severe Traveller’s Diarrhea

A

Anti-motility agents
increase curation of infection

57
Q

Clostridium Difficile
Diarrhea

A

Gram positive anaerobic bacteria
Spore forming
Toxin A and B attack GI mucosal membrane
inflammation, edema, pus

58
Q

Complications
Clostridium Difficile Infections

A

Mild infection
- abdominal pain, nausea, vomiting, anorexia, diarrhea, fever

Severe infection
- toxic megacolon, pseudomembranous colitis, colon perforation, sepsis, death

59
Q

Treatment
Clostridium Difficile Infections

A
  1. ORAL
  2. Antibiotic therapy
    - Vancomycin OR
    - Metronidazole

30% Re-occurance rate
1. Vancomycin, QID, 10 days
2. Rifaxamin TID, 20 days

60
Q

Etiology
Clostridium Difficile

A
  • fluroquinolones
  • tetracyclines
  • cephalosporins
  • PPIs
  • can occur up to 6 weeks after D/C
  • proton pump inhibitors
  • ingestion spores
61
Q

MOA
Fluroquinolones

A

Inhibit DNA gyrase (supercoils DNA for replication) and DNA topoisomerase (daughter strands cannot separate)

62
Q

Indication
Fluroquinolones

A

Indication
moderate-severe traveller’s diarrhea

Abx. Spectrum
Gram positive, gram negative, pseudomonas

63
Q

SE/AE
Fluroquinolones

A

Prolonged QT interval

C. Diff infections: N/V/D

Phototoxicity

Tendon ruptures
- greater risk elderly, glucocorticoids, children, transplants

Teratogenic

64
Q

MOA
Azithromycin

A

Macrolide antibiotic

Inhibits 50S ribosomal subunit, bacteriostatic, prevents replication

65
Q

Indication
Azithromycin

A

Moderate-Severe Travellers diarrhea

Antibiotic spectrum
Gram positive and gram negative bacteria

66
Q

SE/AE
Azithromycin

A

Prolonged QT interval

N/V/Metallic Taste in mouth

Ototoxicity

67
Q

MOA
Vancomycin

A

Binds cell wall precursors, preventing synthesis of cell wall

bacteria cell lysis and death results

68
Q

Indication
Vancomycin

A

Gram positive bacteria and MRSA

C. diff infection

69
Q

SE/AE
Vancomycin

A

Nephrotoxic
Ototoxicity
Bleeding risk

*safe in pregnancy

70
Q

MOA
Metronidazole

A

Antibiotic spectrum
anaerobic bacteria - convert prodrug into active form which damages DNA

71
Q

Indication
Metronidazole

A

Anaerobic bacterial infections and protozoa

C. difficile
Quadruple therapy for PUD

Amox/meteonidazole + clarithromycin/levooxacin + ppi

Bismuth + tetracycline + metronidazole + ppi

72
Q

SE/AE
Metronidazole

A

N/V/HA/Dizziness

Disulfram reaction with alcohol
Inhibits aldehyde dehydrogenase

Hepatitis

73
Q

Crohn’s Disease
Treatment Pathways

A
  1. Mild Disease
    - Induction and maintenance remission 5-ASA (sulfasalazine, methalazine)
  2. Mild-Moderate Disease
    - Induction remission budesonide
    - maintenance remission 5-ASA
  3. Moderate to severe disease
    - Induction and maintenance remission

Tumour necrosis factor alpha (infliximab, adalimumab) + Methotrexate OR Thiopurine (Azathiopurine/Mercaptopurine)

74
Q

5-ASA
Examples

A
  1. Sulfasalazine (metbaolized to 5-ASA and sulfapyridine)
  2. Mesalazine (no sulfa moiety, less SE)
75
Q

5-ASA
MOA

A
  1. Inhibit COX formation of prostaglandins
  2. Inhibit migration of inflammatory cells to site of action
76
Q

5-ASA
Indication

A

Induction and maintenance of remission mild-moderate IBD

77
Q

5-ASA
SE/AE

A

Locally acting
Inactivated by first pass effect

Sulfa moiety: nausea, fever, rash, arthralgia

78
Q

5-ASA
Prescriber considerations

A

Safe in pregnancy and breast feeding

Monitor CBC and diff

79
Q

Budesonide
MOA

A

Anti-inflammatory and immunosupression

Prevents transcription of inflammatory genes and inhibits formation of cytokines (TNF, IL)

Inhibits activation of pro-inflammatory cells: macrophages, neutrophils, T cells, dendrites, etc.

80
Q

Budesonide
INdication

A

Enterocort EC
release in ileum and cecum
induction of remission in mild-moderate collitis not responsive to first line 5-ASA

81
Q

Budesonide
SE/AE

A

Minimal systemic effects
inactivated by first pass effect

82
Q

Anti-Tumour Necrosis Factor alpha (TNF alpha)
Examples

A

Infliximab
Adalimumab

83
Q

Anti-TNF alpha
MOA

A

Block the effect of TNF alpha

pro-inflammatory cytokine
responsible for recruitment inflammatory cells and immune response (fever)

84
Q

Anti TNF alpha
SE/AE

A

BLACK BOX WARNING:
- increase risk for serious and fatal infections
- bacterial
- fungal
- TB and HBV

Infusion reactions:
- flu like symptoms
- fever, HA, chills, dyspnea, hypotension, anaphylaxis

Rare:
- heart, liver failure
- cancer
- allergic reactions

85
Q

Prescriber considerations
anti TNF alpha

A
  • no live vaccinations
  • screen for opportunistic infections (HBV, TB)
86
Q

Methotrexate
Indication

A

Induction and maintenance of remission with anti-TNF alpha therapy of moderate-severe CDM

87
Q

Methotrexate
MOA

A

folate anatonist

inhibition of B and T cells

onset: 3-6 weeks

88
Q

Methotrexate
SE/AE

A

Hepatic fibrosis

bone marrow supression

pneumonitis

GI ulceration

Teratogenic

Reduced life expectancy: CVE, cancer, infection

89
Q

Prescribing considerations
Methotrexate

A

Monitor
- CBC and diff
- Kidney and liver function
- lung function
- screen for pregnancy
- screen for TB, HBV, infections
- no live vaccines
- no alcohol

90
Q

Thiopurines
Examples

A
  1. Azithioprine (pro drug)
  2. Mercaptopurine (active drug)
91
Q

Thiopurine
Indication

A

Maintenance of remission with anti-TNF alpha, moderate to severe disease

Onset delayed: 6 months

92
Q

Thiopurine
SE/AE

A

hepatitis

blood dyscaria

malignancy

93
Q

Ulcerative Colitis (UC)
Treatment Pathways

A
  1. Mild disease
    Induction 5-ASA
    rectal suppository: proctitis
    enema: L sided colitis
    oral: pancolitis
  2. Mild-moderate disease
    Induction 5-ASA with oral budesonide MMX
    Second line: prednisone systemic corticosteroid
  3. Moderate-Severe Disease

Induction and maintenance: anti-TNF alpha + Thiopurines

Induction and maintenance: Vedolizumab (integrin blocker, monoclonal antibody) + thiopurine

94
Q

Which drug is not used in Ulcerative Colitis

A

Methotrexate

95
Q

5-ASA is more effective in which disease?

A

Ulcerative colitis

96
Q

Special population
UC and CD treatment in pregnancy

A

Continue 5-ASA and suppliment with folic acid

Methotrexate is teratogenic

Budesonide has minimal systemic effect and is safe

Infliximab and adalimumab are safe in pregnancy

Year 1: Patho/Pharm (39 decks)

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