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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
Opiod Receptor Antagonists: - Alvimopan (oral) - Methylnaltrexone (SC)
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
26
Use of Antidiarrheal Agents
mild-moderate acute diarrhea, diarrhea caused by IBS or IBD DON'T use in: blood diarrhea, high fever, systemic toxicity, worsening diarrhea despite tx
27
What are the Anti-diarrheal agents?
Opioid Agonists: - Diphenoxylate - Loperamide Bile Salt-Binding Resins - Cholestyramine - Octreotide
28
Diphenoxylate: admin, A/E
- Always given orally with ATROPINE to discourage overdose (but this can cause anti-cholinergic AE) - Crosses BBB → CNS effects
29
Does loperamide cross BBB?
No → no significant analgesic properties or addiction potential
30
Cholestyramine
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
Octreotide
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
Irritable Bowel Syndrome treatment of Chronic abdominal pain
Low dose of tricyclic anti-depressants
33
Alosetron
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
Dicyclomine
Spasmolytic: Non-specific muscarinic receptor antagonist T/U: functional bowel/IBS
35
Anti-emetic Agents
Ondansetron Neurokinin Receptor Antagonists: - Aprepitant - Fosapretant Cannabinoid: - Dronabinol
36
Ondansetron
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
Neurokinin Receptor Antagonists: - Aprepitant (oral) - Fosaprepitant (parenteral)
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
Dronabinol
Cannabinoid: psychoactive T/U: Chemo-induced N&V in combo w/ phenothiazines - Increase appetite A/E: abuse, dependency & withdrawal
39
Aminosalicylates - Mesalamine - Sulfasalazine
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
Sulfasalazine: - Pharm - A/E
Azo carrier allows absorption in terminal ileum & colon BUT A/E: myelosuppression, ↓ folic acid absorp, oligospermia, headache, Muscle pain, hypersensitivity (sulfa)
41
How do you treat GI Inflammation as opposed to inflammation elsewhere?
Use aminosalicylates instead of NSAIDs
42
First choice for moderate-severe active IBD?
Prednisolone, Prednisone
43
Which Glucocorticoid is given as an enema / foam / suppository?
Hydrocortisone
44
Which glucocorticoid is given for Chron's Disease (@ distal colon)
Budesonide
45
Anti-Metabolites: - Mercaptopurine - Azaothioprine
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
Pharm of mercaptopurine & azaothioprine
azathioprine → mercaptopurine mercaptopurine --XO--> inactive metabolite mercaptopurine --TPMT--> active thioguanine nucleotides
47
Methotrexate
``` 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
Infliximab
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
Natalizumab
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
Ursodiol
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
What drug is used for chronic constipation that works by forming a bulky emollient gel?
Methylcellulose, psyllium
52
What drugs are given to promote complete colonic cleansing?
PEG + electrolytes +/- Bisacodyl
53
What is the mechanism of Alosetron?
For severe diarrheal IBS-- Inhibits enteric cholinergic neuron 5-HT3 receptors
54
Drug associated with TB or opportunistic infection?
Infliximab: used for Chron's-- supresses cytokine release by binding TNF
55
What is the Mechanism of Infliximab?
Binds soluble & membrane bound TNF, thereby suppressing cytokine release...
56
What effect does Loperamide have on the brain?
Minimal- poor distribution to CNS. muahaha
57
What drug would you use for Portal Hypertension and what is its MOA?
Octerotide: somatostatin-receptor agonist
58
What drug works on Type 2 Chloride channels (CLC-2)?
Lubiprostone- for constipation IBS
59
What drug would you give for severe constipation and daily laxative therapy?
Lactulose-- increases stool liquidity due to an obligate increase in fecal fluid
60
What three drugs can be used for chemo induced N/V?
- Ondansetron (for acute only) - Aprepitant (acute & delayed) - Dronabinol
61
Mechanism of Ondansetron?
5-HT3 receptor inhibition in CTZ
62
Which drugs directly induce the JAK-STAT pathway?
Interferon alfas
63
Which HBV drug are you most likely to see resistance develop?
Telbivudine
64
Which anti-HBV has almost 100% oral bioavailability on an empty stomach?
Entecavir (inh all 3 fx of HBV-RT)
65
HCV standard treatment regimen?
IFN-a2b, ribavirin

S4M2 (10 decks)

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