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S4M2 > GI Pharm > Flashcards

GI Pharm Flashcards

1
Q

Goal of HBV treatment

A

Suppress HBV DNA to undetectable levels
Seroconversion of HBeAg from (+) to (-)
Reduction in elevated liver transaminase levels

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2
Q

Goal of HCV treatment

A
  1. Viral Eradication –> Sustained viral response (absence of detectable viremia for 6mo after therapy) –> decr risk of HCC & cirrhosis
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3
Q

Current Tx strategy of HCV infection

A

Weekly administration of INF-a AND daily Ribavirin

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4
Q

MoA of INF-a

A

SC/IM/IV admin
Induces JAK-STAT pw
–> nuclear translocation of cell protein complex that binds genes w/INF-specific response element
–> induces expression of viral resistance genes
—–inh of viral penetration,etc
—–incr expression of MHC ag, incr phagocyte activity of Macrophages

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5
Q

Interferon Tx of HBV infection

A

INF a-2B

PegINF a-2A

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6
Q

Interferon tx of HCV infx

A

All 4 (INF a-2B, a-con-1; PegINF a-2A, a-2B)

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7
Q

Treatment of Condylomata acuminate

A

Genital warts caused by papilloma virus

Tx: INF a-2B

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8
Q

A/E of IFN-a tx

A

Flu-like syndrome
Alopecia
Mood disorder/depression/suicide

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9
Q

Adefovir MOA & TU

A

adenine analog– phosphorylated x2

Competitively Inhibits HBV reverse transcriptase –> chain termination

Reduces HBV DNA levels by 99% (BUT slow & least likely to induce HBeAg seroconversion)

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10
Q

Adefovir A/E

A

Nephrotoxicity
Lactic acidosis
Hepatomegaly w/steatosis
HBV exacerbation

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11
Q

Entecavir Pharm, MOA & T/U

A

Guanosine nucleoside analog
100% oral bioavailability on empty stomach

Competitively inhibits all 3 fx of HBV-RT (base priming, reverse transcrip of neg strand from pregenomic RNA, synth of + strand of HBV DNA)

For CHRONIC HBV infection w/active replication & persisten elevations in serum aminotransferase

Resistance is rare

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12
Q

Lamivudine- pharm, MOA, T/U, A/E

A

3x phosphorylated, oral

Inhibits HIV & HBV-RT enzymes by competing w/deoxycytidine triphosphate for incorp into viral DNA (-> chain term)

HBV, HIV-1, & HIV-2 infx in adults & children

A/E: pancreatitis in pts with BOTH HIV & HBV infx. Mitochondrial toxicity + lactic acidosis

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13
Q

What anti-Hepatitis drug are you MOST likely to see resistance with?

A

Telbivudine (25% after 2 years)

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14
Q

Telbivudine:
MOA
T/U
A/E

A

Thymidine nucleoside analog

Competitively inhibits HBV-RT

Chronic HBV in adults

A/E: BLACK BOX for HBV exacerbation after discontinuation, lactic acidosis, severe hepatomegaly
High resistance

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15
Q

Ribavirin:
MOA
T/U
A/E

A

Purine nucleoside analog w/D-RIBOSE sugar.
Higher oral BA w/fatty meals, lower w/antacids

Unclear MOA– may interfere w/GTP & viral RNA-dep Pol synthesis

T/U: HCV infection (in combo w/INF-a)
Also, RSV (aerosol), Lassa Fever, Viral Hemm Fevers, Measles pneumonitis, Encephalitides

A/E: ALWAYS GIVE w/IFN-a to protect from HEMOLYTIC ANEMIA
Teratogenic!!! (partner can’t take either)

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16
Q

Telaprevir & Boceprevir
MOA
T/U

A

Target viral proteases NS3A, NS4A

For HCV genotype 1 infection (only for previously untreated or previous IFN-a/Ribavirin tx failure)
— still ALWAYS use in combo with IFN-a & Ribavirin!!!

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17
Q

What are the subclasses of Laxatives?

A
  • Bulk Forming
  • Stool Softeners
  • Osmotic
  • Stimulants (Cathartics)
  • Chloride channel activators
  • Opioid Receptor Antagonists
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18
Q

Bulk forming laxatives: MOA

  • Methylcellulose
  • Psyllium
A

MOA: absorption of water –> emollient gel, causes distension of colon, promoting peristalsis

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19
Q

Stool softeners: MoA

  • Docusate
  • Mineral Oil
A

↓ surface tension → permits water & lipids to penetrate stool

(mineral oil aslo lubricates stool, retarding water-absorption)

Docusate is oral AND rectal; mineral oil oral only

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20
Q

Mineral oil A/E

A

Aspiration can cause severe lipid pneumonitis; impaired fat-sol vitamin absorption

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21
Q

Lactulose: MoA

A

Osmotic laxative– soluble but non-absorbable → obligate ↑ fecal fluid

*pt must maintain adequate hydration to compensate for fluid loss

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22
Q

Balanced Polyethylene Glycol: T/U

A

Osmotic laxative used for complete colonic cleansing before GI endoscopic procedures

Small doses taken to treat/prevent chronic constipation

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23
Q

Stimulant/Cathartic Laxatives: MOA, T/U, A/E

  • Senna (natural plant)
  • Bisacodyl
A

not sure, but may DIRECTLY STIMULATE ENS & colonic electrolyte/fluid secretion

T/U: constipation; colonic cleansing for colonoscopy (Bisacodyl)

A/E: Cathartic Colon (n. damage due to abuse); Melanosis coli (brown pigmentation- w/Senna)

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24
Q

Chloride Channel Activator: Lubiprostone

A

MOA: Stimulates type 2 Cl- channel (CLC-2) in small intestine
→ ↑ Cl-rich fluid secretion into intestine → stim intestinal motility, shorten intestinal transit time

T/U: IBS w/predominant constipation

A/E: N&V

C/I: pregnancy

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25
Q

Opiod Receptor Antagonists:

  • Alvimopan (oral)
  • Methylnaltrexone (SC)
A

Peripheral mu-opiod receptor antagonist

T/U:
Alvimopan: shorten period of post-operative ileus (don’t take for >7days)
Methylnatrexone: opioid-induced constipation

A/E: Alvimopan → cardiotoxicity– only given in hospital

**no analgesia effect on CNS

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26
Q

Use of Antidiarrheal Agents

A

mild-moderate acute diarrhea, diarrhea caused by IBS or IBD

DON’T use in: blood diarrhea, high fever, systemic toxicity, worsening diarrhea despite tx

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27
Q

What are the Anti-diarrheal agents?

A

Opioid Agonists:

  • Diphenoxylate
  • Loperamide

Bile Salt-Binding Resins

  • Cholestyramine
  • Octreotide
28
Q

Diphenoxylate: admin, A/E

A
  • Always given orally with ATROPINE to discourage overdose (but this can cause anti-cholinergic AE)
  • Crosses BBB → CNS effects
29
Q

Does loperamide cross BBB?

A

No → no significant analgesic properties or addiction potential

30
Q

Cholestyramine

A

MOA: binds bile acids @ intestinal lumen & prevent reabsorption

T/U: Diarrhea caused by excess fecal bile acids

A/E: ↓folic acid absorption, steatorrhea

C/I: diverticulitis, strongly charged drugs (warfarin)

31
Q

Octreotide

A

MOA: Somatostatin receptor agonist

Admin: SC or once/mo depot IM

T/U:

  • secretory diarrhea
  • systemic sx from carcinoid tumor & VIPoma
  • AIDS, short bowel diarrhea
  • ↓ portal flow & varicose pressure in pts w/ cirrhosis & portal HTN
  • Pitutary tumor tx
  • GI bleeding in kids
  • Acromegaly (1st line after surgery)
  • Hypoglycemia & Hyperinsulinemia in infancy
32
Q

Irritable Bowel Syndrome treatment of Chronic abdominal pain

A

Low dose of tricyclic anti-depressants

33
Q

Alosetron

A

Potent & selective 5-HT3 receptor antagonist → inh unpleasant sensation, inh colonic motility, ↑ total colonic transit time

T/U: women with severe diarrhea-predominant IBS

A/E: BLACK BOX FOR GI TOXICITY– must be part of prometheus program
Constipation in 30%

34
Q

Dicyclomine

A

Spasmolytic: Non-specific muscarinic receptor antagonist

T/U: functional bowel/IBS

35
Q

Anti-emetic Agents

A

Ondansetron

Neurokinin Receptor Antagonists:

  • Aprepitant
  • Fosapretant

Cannabinoid:
- Dronabinol

36
Q

Ondansetron

A

MOA: Inh 5-HT3 receptors @ vomiting center, CTZ, extrinsic intestinal vagal, & spinal afferent nn.

T/U:

  1. Prevent ACUTE chemo-induced N&V (give IV 30min prior) along w/glucocorticoid, NK1-receptor antag
    - Also, prevention & tx of post-op & post-radiation N&V

A/E: QT prolongation

37
Q

Neurokinin Receptor Antagonists:

  • Aprepitant (oral)
  • Fosaprepitant (parenteral)
A

MOA: antagonist @ NK1-R in brain → central blockade of area postrema

T/U: acute AND delayed chemo-induced emesis

  • both cross BBB

C/I: warfarin

38
Q

Dronabinol

A

Cannabinoid: psychoactive

T/U: Chemo-induced N&V in combo w/ phenothiazines
- Increase appetite

A/E: abuse, dependency & withdrawal

39
Q

Aminosalicylates

  • Mesalamine
  • Sulfasalazine
A

MOA:

  • Anti-inflammatory:inh production of pro-inflamm cytokines, activity of NF-kB, fx of NK cells/mucosal lymphocytes/ macrophages;
  • Scavenge ROS;
  • Modulate inflamm mediators from COX & LOX pws

T/U: 1st line for mild-moderate UC & CD (in colon or distal ileum)

40
Q

Sulfasalazine:

  • Pharm
  • A/E
A

Azo carrier allows absorption in terminal ileum & colon
BUT
A/E: myelosuppression, ↓ folic acid absorp, oligospermia, headache, Muscle pain, hypersensitivity (sulfa)

41
Q

How do you treat GI Inflammation as opposed to inflammation elsewhere?

A

Use aminosalicylates instead of NSAIDs

42
Q

First choice for moderate-severe active IBD?

A

Prednisolone, Prednisone

43
Q

Which Glucocorticoid is given as an enema / foam / suppository?

A

Hydrocortisone

44
Q

Which glucocorticoid is given for Chron’s Disease (@ distal colon)

A

Budesonide

45
Q

Anti-Metabolites:

  • Mercaptopurine
  • Azaothioprine
A

MOA: Inhibits enzymes involved in de novo purine nucleotide synth

T/U: induction & maintenance of remission of IBD

A/E: myelosuppression

C/I: pregnancy, TPMT defx (mercaptopurine)- prescreen

46
Q

Pharm of mercaptopurine & azaothioprine

A

azathioprine → mercaptopurine
mercaptopurine –XO–> inactive metabolite
mercaptopurine –TPMT–> active thioguanine nucleotides

47
Q

Methotrexate

A 
MOA: inhibits enzymatic fx of DHF-red → block synth of THF from Folic Acid
→ inh cell prolif
→ interfere w/ IL-1 actions
→ ↑ adenosine release
→ apoptosis of activated T-lymphocytes

T/U: induction & maintenance of CD remission

48
Q

Infliximab

A

Anti-TNF agent: binds & neutralizes soluble & membrane-bound TNF
→ reverse signaling

T/U: mod-severe IBD in pts who have INADEQUATE RESPONSE to conventional tx
1/3 pts lose response

A/E: opportunistic infx (TB!!!- take PPD test + prophylaxis for (+) result)

  • infusion/injection rxn
  • headache, HTN, SOB
49
Q

Natalizumab

A

Anti-Integrin Agent: binds & neutralizes a4 subunit of integrin

T/U: mod-severe CD in pts who have failed other tx

A/E: Progressive Multifocal Leukoencephalopathy (reactivation of JC virus)

BLACK BOX WARNING for PML risk (TOUCH program distribution)

50
Q

Ursodiol

A

MOA: ↓ cholesterol content of bile by ↓ hepatic cholesterol secretion
→ expand bile acid pool
→ dissolves gallstones

T/U: dissolution of small chol gallstones for non-surgery pts
- prevent gallstones in obese pts undergoing rapid weight loss

51
Q

What drug is used for chronic constipation that works by forming a bulky emollient gel?

A

Methylcellulose, psyllium

52
Q

What drugs are given to promote complete colonic cleansing?

A

PEG + electrolytes +/- Bisacodyl

53
Q

What is the mechanism of Alosetron?

A

For severe diarrheal IBS– Inhibits enteric cholinergic neuron 5-HT3 receptors

54
Q

Drug associated with TB or opportunistic infection?

A

Infliximab: used for Chron’s– supresses cytokine release by binding TNF

55
Q

What is the Mechanism of Infliximab?

A

Binds soluble & membrane bound TNF, thereby suppressing cytokine release…

56
Q

What effect does Loperamide have on the brain?

A

Minimal- poor distribution to CNS. muahaha

57
Q

What drug would you use for Portal Hypertension and what is its MOA?

A

Octerotide: somatostatin-receptor agonist

58
Q

What drug works on Type 2 Chloride channels (CLC-2)?

A

Lubiprostone- for constipation IBS

59
Q

What drug would you give for severe constipation and daily laxative therapy?

A

Lactulose– increases stool liquidity due to an obligate increase in fecal fluid

60
Q

What three drugs can be used for chemo induced N/V?

A
  • Ondansetron (for acute only)
  • Aprepitant (acute & delayed)
  • Dronabinol
61
Q

Mechanism of Ondansetron?

A

5-HT3 receptor inhibition in CTZ

62
Q

Which drugs directly induce the JAK-STAT pathway?

A

Interferon alfas

63
Q

Which HBV drug are you most likely to see resistance develop?

A

Telbivudine

64
Q

Which anti-HBV has almost 100% oral bioavailability on an empty stomach?

A

Entecavir (inh all 3 fx of HBV-RT)

65
Q

HCV standard treatment regimen?

A

IFN-a2b, ribavirin

S4M2 (10 decks)

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