03-03 GI PHARM Flashcards Preview

SBM GI > 03-03 GI PHARM > Flashcards

Flashcards in 03-03 GI PHARM Deck (29)
Loading flashcards...
1
Q

REVIEW: Motility physio

  • What are the main positive (pro-motility) GI neurotransmitters?
  • The main negative ones?
A

Positive: ACh and Substance P

  • Stimulate contraction by ↑ [Ca2+]

Negative: NO and VIP

  • Maintain relaxation downstream
  • Nice review of mechanism on slide 24.*
2
Q

neostigmine

  • Indication
  • MoA?
  • Drawback?
A
  • used rarely after surgery for acute colonic pseudo-obstruction or paralytic ileus
  • reverisble acetylcholinesterase inhibitor → ↑ ACh bioavailability
    • competitive inhib (ACh look-alike)
  • problem is that they act too generally throughout the body to be very useful
3
Q

domperidone

  • Indication?
  • MoA?
  • How is this improvement over older drugs in class (give example)?
  • ADRs?
A
  • Prokinetic agent but not approved by FDA, only experimental
  • inhibits the inhibition by blocking dopamine (D2) receptors in myenteric plexus
    • does not penetrate CNS as did older drugs (e.g. phenothiazines)
  • ADRs: 2013 EU study showed ↑ CVD risk
4
Q

metoclopramide

  • Indication(s)?
  • MoA?
  • ADRs?
A

Indications

  • promotility agent; anti-emetic

MoA

  • PRIMARY: stimulates 5-HT4-R on enteric interneurons → ACh release → ↑ gastric emptying + faster transit time thru small bowel via…
    • …↑ resting LES tone
    • …↑ gastric tone/peristalsis
    • …relaxes pylorus
    • …↑ duodenal peristalsis
    • no effect on secretions or colon contractions
  • SECONDARY: inhib’s inhib of dop. at D2-R (like domperidone)

ADRs

  • rarely: extrapyramidal SEs
  • ↑er risk when co-Rx’d w/ domperidone; in kids/teens
5
Q

erythromycin

  • Indications
  • MoA
  • ADRs?
A

Indications

  • gastroparesis

MoA

  • motilin (re-call = peptide that reg’s MMC) receptor agonist
  • enhances upper GI motility (not so much lower GI)

ADRs

  • tolerance develops
  • antibiotic effects
6
Q

Re-cap the prokinetic drugs we learned

  • basic MoA?
A
  1. neostigmine
    • acetylcholinesterase inhibitor
    • works at enteric neuro-muscular jct
  2. domperidone
    • inhibits the inhibiton of dopamine
    • D2-receptor antagonist
  3. metoclopramide
    • 1° 5HT4-R agonist; 2° D2-R antagonist
  4. erythromycin
    • motilin receptor agonist

These accentuate natural rhythm already there

7
Q

REVIEW: nausea physio

  • Name brain region responsible
  • receptors involved?
A

CTZ (chemoreceptor trigger zone)

  • previously thought to be area of medulla w/o BBB
    • ?evolved to sense toxins
  • Now ?loosely organized network → “central pattern generator”
  • receptors: 5HT3-R, D2-R, M1-R, CB1-R
8
Q

phenothiazine

  • Indication
  • MoA
  • similar drugs
  • ADRs
A

An example drug is promethazine

  • Indication: nausea in acute emergent situations
    • extrapyramidal ADRs too risky for chronic use
  • MoA: D2R antagonist
  • similar drugs: metoclopramide, domperidone
    • hi-dose metoclopramide is really good for chemo-related nausea but higher dose = higher risk for EPS
9
Q

ondansetron

  • Indication
  • MoA
  • ADRs
A

ondansetron

  • Indication: nausea (esp chemo, radiation, pregnancy and ~post-op)
    • same efficacy as metoclopramide
    • safer but $$
  • MoA: 5HT3-R antagonist
    • acts both on GIT’s vagal 5HT3-R (thought to be 1° MoA) and CNS R’s
  • ADRs: few, no EPS ADRs like metoclopramide
10
Q

dronabinol

  • Indication
  • MoA
  • ADRs
A

dronabinol

  • Indication:
    • prophylax for chemo n/v
    • appetite stim in HIV/AIDS
  • MoA: agonizes canabinoid-R’s → appetite
  • ADRs: abuse and ADRs “related to complex CNS actions”
11
Q

diphenhydramine

  • indicated for?
  • MoA?
A
  • mild-mod motion sickness
  • H1 antagonist
12
Q

scopalamine

  • indication?
  • ADR?
A
  • motion sickness, vestibular d/o
  • Muscarinic antagonists
13
Q

Chemo anti-nausea Rx is often given as a combo of drugs. What drug is usually given with them?

A

dexamethasone is most commonly agent in comboination anti-emetic tx

14
Q

Ginger

  • Shown to work for?
  • MoA?
A

Ginger is indicated for

  • motion sickness, post-op nausea and morning sickness
  • less convincing evidence for chemo n/v
  • influences gastric emptying in healthy pts

MoA

  • shogaols and gingerols stim saliva, bile and gastric secretions
  • some 5HT-3 interaction
  • some ginger preperations inhib TXA2 and platlet aggregation
15
Q

What are the anti-emetic drugs we learned?

  • MoA (SparkNotes edition)?
A
  1. metoclopramide
    • D2-R (dopamine) antagonist
  2. phenothiazines (e.g. promethazine)
    • D2-R antagonist
  3. ondansetron
    • 5HT3-R antagonist
  4. dronabinol
    • canabinoid agonist
  5. diphenhydramine
    • H1 antagonist
  6. ginger
    • shogaols and gingerols stim saliva, bile and gastric secretions
    • 5HT-3 interaction
16
Q

What heartburn/GERD meds did we cover?

A

Mg- and Al- hydroxides, Cimetidine, omeprazole

17
Q

Mg- and Al- hydroxide

  • MoA
  • Most effective preparation
  • ADRs
A
  • MoA: direct neutralization of acid
  • Al/Mg liquid preperations are the best
  • ADRs
    • Al(OH)3 - can have constipating effect
    • Mg(OH)2 - can have laxative effect
18
Q

cimetidine

  • MoA
  • Equally effective sister drugs w/ fewer ADRs
  • ADRs
A

MoA

  • H2 receptor antagonist → ↓ basal (e.g. nocturnal) H+ secretion

Sister Drug

  • famotidine (brand = Pepcid AC) and ranitidine (Zantac)

ADRs

  • P450 inhibition → increases half-life of P450 metabolized drugs
19
Q

omeprazole

  • Indications
  • MoA
  • ADRs
A

Indications

  • GERD
  • PUD (shown more effective at encouraging ucler healing than H2 antagonists)

MoA

  • PPIs are pro-drugs that covalently bind the proton pump irreversibly inhibiting it
  • major difference betwen the PPIs is their kinetics; equal efficacy otherwise

ADRs

  • may inhibit some P450s (warfarin and BZDs)
  • ∆s in pH can affect absorption of other Rxs
20
Q

What diarrhea tx options did we learn?

  • MoA SparkNotes
A

oral rehydration therapy

  • fluid repletion

metamucil

  • bulk-forming but mech unknown

loperamide (Immodium)

  • opiod agonist, 40X more potent at slowing poop than morphine

Pepto (bismuth subsalicylate)

  • mech unknown, safe but causes black stools
21
Q

What IBS treatment options did we cover?

  • SparkNotes MoA
A

alosetron

  • 5HT3 antagonist

tegaserod (Zelnorm)

  • 5HT4 agonist
22
Q

alosetron

  • Indicated for?
  • MoA
  • ADRs?
A

Indicated only for women with IBS-D who have failed other tx

MoA

  • 5HT3 receptor antagonist
    • recall drugs ending in “setron” are serotonergic
    • e.g. ondansetron
  • Reduces:
    • intestinal motility
    • sensitivity to distention
  • Theory is that:
    • ↓ plasma [5HT] is assoc’d w/ IBS-C and
    • ↑ plasma [5HT] assoc’d w/ IBS-D

ADRs

  • rare but serious ischemic colitis
  • Was pulled off market and then returned in 2002 w/ limited marketing capability
23
Q

tegaserod (Zelnorm, a.k.a. creepy belly ad drug)

A

Indicated:

  • IBS-C in women
  • chronic constipation

MoA

  • 5HT4 agonist
  • Theory is that:
    • ↓ plasma [5HT] is assoc’d w/ IBS-C
    • ↑ plasma [5HT] assoc’d w/ IBS-D

ADRs

  • heart attack, stroke, unstable angina
  • pulled off market for a while
  • now only on emergency basis

Available in U.S. under an emergency investigational new drug (IND) process. Emergency situations are defined as immediately life-threatening or requiring hospitalization. Physicians with patients who may qualify can contact the FDA’s Division of Drug Information. The FDA may either deny the request or authorize shipment of Zelnorm® by Novartis.

24
Q

What IBD tx did we learn?

A
  • sulfasalazine/mesalamine
  • prednisone
  • budesonide
  • azathioprine/6-MCP
  • MTX
  • infliximab
25
Q

sulfasalazine/mesalamine

  • Indicated for
  • MoA
  • ADRs
A

Indications

  • Mild-to-Moderate UC
  • More effective in UC than Crohn’s

MoA

  • Sulfasalazine: prodrug not absorbed in upper GI tract cleaved by bacteria into
    • sulfapyridine ~toxic metabolite AND…
    • Mesalamine (5-aminosalicylic acid, or 5-ASA): active metabolite
      • would be absorbed in upper GIT if given PO unless packaged specially
        • e.g. Pentasa (PO mesalamine in time-release capsules)
        • e.g. Asacol (PO mesalamien in pH-sensitive capsules)

ADRs

  • few b/c not absorbed much systemically?
  • nothing in slides
26
Q

azathioprine/6-MCP

A

Indications

  • mod-to-severe IBD

MoA

  • most commonly used immunosuppressives, but take several weeks to kick in
    • need steroids to bridge ‘til that time
  • azathioprine is prodrug of 6-MCP
    • either works well
    • could also consider MTX

ADRs

  • bone marrow suppress
  • leukopenia
  • teratogenesis
27
Q

infliximab (Remicade)

A

infliximab (Remicade)

  • TNFα inhibitor used to control IBD
  • adalimumab (Humira) and certolizumab (Cimzia) are also anti-TNFα used in IBD
28
Q

constipation drugs basics (not on drug list on first slide)

A

physical activity, regular b.m schedule, increased fiber and water intake

stool-wetting agents actually have very minimal effect

stimulant laxatives cause mild inflammation

See image

29
Q

Why is budesonide better than prednisone for mod-to-severe IBD?

A

extensively removed in first-pass metabolism, therefore can be packaged to be released only in terminal ileum where it acts locally but then is most filtered out by liver before systemic

  • pricier