Pharm- GI Flashcards
Hep A- how do you get it? what type of contact
person to person: fecal oral
come in contact with infected feces somehow—happens a lot through contaminated food
symptoms of Hep A
nausea loss of appetite fever jaundice elevated liver enzymes
in Hep A the virus can _____ outside of the body for several months
live.
doesn’t have machinery to live on its own, it is waiting for a host. but it is still viable for several months before it comes into contact with a host
People that have Hep A will have what type of serology?
vs
People that are immune to Hep A (either from past infection or vaccination) will have what type of serology?
Indicates current or recent infection with hepatitis A=Anti-HAV IgM (IgM antibody to hepatitis A):
Indicates immunity: Anti-HAV IgG (IgG antibody to hepatitis A):
Does Hep A become chronic? Explain
HAV does not become chronic
you either get better or you die (there is no continuity—not like AIDS)
-once you have it, you show anti HAV immunoglobulins. So you can’t get it again.
(patients will demonstrate lifelong anti-HAV IgG)
What are some ways that people can contract Hep A?
- traveling outside of the US
- men who have sex with men
- drug abuse
- working with primates
Can Hep A be contracted vertically?
We do not think this can be contracted vertically (moms cant give to babies)
Are People that already have liver disease more likely to acquire Hep A?
no. they are not more likely to acquire Hep A, but if they somehow do get it, the liver is already damaged so their prognosis is not good. They will progress more rapidly through stages of Hep A.
HAV phases of the illness
- incubation (10-50 days): asymptomatic
- prodromal/preicteric: several days, symptoms start
- Icteric: within 10days of initial symptoms- jaundice: this is when patient seeks help because they realize they are actually really sick
- convalescence
Specifics on the Icteric Phase of Hep A
viremia ends soon after hepatitis begins
fecal infection remains for up to 2 weeks
in rare cases hepatic necrosis can occur:
-high fever
-pain
-vomiting
-jaundice
-hepatic encephalopathy
Symptoms of Hep A last about ______ And most people recover fully by _______
2mos, 6mos
If pt with Hep A develops necrosis (in some rare cases) 70-90% of those patients _____ and if you are over 50 ….
die, no chance of surviving it
Not everyone with hep A develops liver necrosis though—this is just talking about if you DO develop it.
HAV prevention and prophylaxis:
Vaccination – HAVRIX, VAQTA, TWINRIX
Hygiene-we have good hygiene in US so its rare
Avoidance-– avoiding places that don’t have proper hygiene
Seroconversion of HAV
Adults 95% after one dose, 100% after two doses
Children 97% after one dose, 100 % after two doses
Prevaccination testing for HAV in US?
- areas where patients may have already been exposed to hep A
- We don’t do this in USA
- ->If you have pt that comes from Africa –do some serology to see if protected on them before you just give them vaccine.
How long does the HAV vaccine give you immunity for?
vaccine gives long term immunity 14-25 years
& brands are interchangeable for the booster
Post-exposure prophylaxis with HAV
-what’s used/preferred?
Vaccine or IgG (immunoglobin)
-vaccine is preferred
How to give IgG for HAV?
Who needs to get IgG as opposed to vaccine?
-Sterile prep of concentrated antibodies against HAV (antibody A)
-Administered IM
-Most effective in first 2 weeks of exposure and before symptomatic
(You would really need to know “someone I know had Hep A and I came into contact with them 2 weeks ago”)
Special populations need to use IgG for the most part
< 12 months
> 40 years old due to risk of severity
if pt is Immunocompromised – vaccine may be ineffective
HAV postexposure prophylaxis..common rare?
Really rare situation
If someone is exposed to hep A we give them vaccine if we can give them vaccine. If they never got vaccine, and then they become exposed and only find out after 2 weeks, we need to give
IgG
Pts less than 12mos old or older than 40yo and exposed, we give them IgG for post exposure to Hep A—but then we can’t give ______for 6mos after IgG admin
live vaccine
Is Hep A similar to Hep B?
no
how do you come infected with Hep b? what type of contact
Percutaneous or mucosal contact with infected blood or body fluids
**it is blood borne
Examples of ways to get Hep B
Bloodborne Sexual contact IV drug use Vertical transmission Contact with open sores or directly with blood Needle sticks
Symptoms of Hep B
Fever Fatigue N/V Abdominal pain Dark urine Jaundice Clay colored stools -the last 4 symptoms are ones that kind of give clues that its Hep B –these are different from Hep A
Can Hep B virus persist outside of the body?
yes for 7 days
can Hep B become Chronic?
Yes! (this is another way it is different from Hep A which does not become chronic)
in Hep B you can die, you can resolve, or you can have it forever
whereas in Hep A you can either die, or resolve it
Does Hep B have vertical transmission?
Yes if mom has Hep B, baby can get Hep B.
also opposite of Hep A which has no vertical transmission
Hep B- how long is incubation phase. will you see symptoms in this phase?
45-160 days
yes
They can not know they have it and incubation and be infected for 4mos
Hep B- symptoms are more common in adults or kids?
symptoms more common in adults
The Prodromal stage/Preicteric stage of Hep B lasts how long, and what is characterized by?
3-10days
true symptomatic phase
Icteric Phase Of Hep B is how long? what characteristics
1-3 weeks, jaundice
Convalescence phase of Hep B –is generally how long and characterized by?
(weeks to months) persistent fatigue (patients are incredibly tired)
Patients currently with Hep B will have what in blood?
HBsAg
Some pts completely recover from Hep B and if they do they will have ____ in blood which means that they have had it, and it resolved
Patients who recover completely will clear HBsAg and demonstrate anti-HBs
Chronic Infection with HBV
- ___% of vertical transmissions become chronic
- ____% of adults who become infected will develop chronic hep B
- patients may be _____ but can infect others
- 90
- 5
- asymptomatic
If you have hap B you have a greater risk of getting
cirrhosis, hepatitis, liver failure, hepatocellular carcinoma
Prevention and Prophylaxis of HBV: use what?
vaccination (recombivax HB, energy-B, twinrix )
-twinrix gives you immunity from Hep A and B at the same time
Seroconversion after vaccination for HBV
adults 90% after 3 doses
children 95% after 3 doses
After age 60, seroconversion rates are below 75% for HBV
Why?
Our older folks do not mount immune responses the same way—as you get older, vaccines become less effective in general. If you want a Hep B vaccine, or pt wants it, it is better to decide earlier rather than later.
is revaccination testing/titer routine with HBV?
no–because if you don’t know if you are immune, instead of getting you tested, they will just give you the vaccine again
Vaccine for Hep B–long or short term immunity?
long, around 20 yrs
Non-responders for Hep B vaccine?
occur in less than 5% (have had 6 doses)
If you’ve had 6 doses and you are still not responding, you are called a nonresponder –you’re just not going to seroconvert
HBV post exposure prophylaxis
Occupational
Unvaccinated + HBsAg positive source
HBIG (1) + HB series
HBV post exposure prophylaxis
Occupational
Unvaccinated + HBsAg negative source
HB series
HBV post exposure prophylaxis
Occupational
Unvaccinated + Unknown source
HB series
HBV post exposure prophylaxis
Occupational
Vaccinated Responder + HBsAg positive source
no treatment
HBV post exposure prophylaxis
Occupational
Vaccinated Responder + HBsAg negative source
no treatment
HBV post exposure prophylaxis
Occupational
Vaccinated Responder + HBsAg unknown source
no treatment
HBV post exposure prophylaxis
Occupational
Vaccinated Non-Responder + HBsAg positive source
HBIG (1) + HB series
OR
HBIG (2)
HBV post exposure prophylaxis
Occupational
Vaccinated Non-Responder + HBsAg negative source
no treatment
HBV post exposure prophylaxis
Occupational
Vaccinated Non-Responder + HBsAg unknown source
if perceived risk, do what you would do for a positive source=
HBIG (1) + HB series
OR
HBIG (2)
HBV post exposure prophylaxis
Occupational
vaccinated with unknown antibody response + HBsAg positive source
test for HBsAg antibodies
if positive: no tx
if negative: HBIG + booster
HBV post exposure prophylaxis
Occupational
vaccinated with unknown antibody response + HBsAg negative source
no tx
HBV post exposure prophylaxis
Occupational
vaccinated with unknown antibody response + HBsAg unknown source
test for HBsAg antibodies
if pos: no tx
if negative: booster and check in 1-2mos
HBV post exposure prophylaxis
NON occupational
unvaccinated with HBsAg positive source
HBIG + HB series
HBV post exposure prophylaxis
NON occupational
unvaccinated with HBsAg unknown source
HB series
HBV post exposure prophylaxis
NON occupational
vaccinated with HBsAg positive source
HB booster dose
HBV post exposure prophylaxis
NON occupational
vaccinated with HBsAg unknown source
no tx
Babies born to HBsAg positive moms should receive
HBIG within 12 hours of birth and begin HB series
Occupational exposure vs.non occupational exposure
Occupational exposure-exposed at work
Nonoccupational exposure-lifestyle issue/or traumatic incident (stabbing)
HBIG what is it?
HB immunoglobulin –> gives you protection right now
then you can also give the series—it protects your for life (or for a long time)
Why is tx different with non-occupational person?
We don’t hve a titer on them, and the exposure is probably worse than in an occupational exposure
HBV goals (chronic tx)
decrease viral load, improve patient’s immune response
Recommended in chronic active disease
NIH does not recommend treatment for Hep B if:
when do we not tx
1) ALT or liver biopsy is normal, regardless of HBV DNA levels–If your liver enzymes are normal, we are not going to treat you
2)HBV DNA present but no HBsAg unless patient is immunosuppressed-
If you have Hep B DNA and you haven’t mounted surface antigens then we are not going to treat you unless you are immunocompromised and your body cannot defend itself
when we DO tx for Hep B, what do we give the patient?
Give pt Interferon alfa (immune system booster)
What is interferon alfa/fxn?
examples of these drugs
Used to tx Hep B- antiviral
Enhances host immune system
Pegintron, Pagasys and Intron
Also know that all these drugs are called interferon Alpha
Interferon alfa is good for treating specifically
HBV glomerulonephritis
Interferon alfa should only be used
in compensated cirrhosis
the liver is heavily scarred but can still perform many important bodily functions
what are some side effects of interferon alfa?
(used for Hep B )
-Flu-like syndrome lasting 24 hours after administration
(Every time they get vaccine this happens)
-Myelosuppression (decrease in bone marrow)
-Chest pain**
-Fatigue
-Alopecia
-Elevated liver enzymes
other antivirals besides interferon alfa to tx Hep B:
**most end in vir or dine Entecavir (Baraclude) --First-line therapy --Good activity and low resistance Tenofovir (Viread)- Lugo uses this the most in pharmacy --First-line therapy alternative Telbivudine (Tyzeka) --Second-line agent Adefovir (Hepsera) --Third-line agent Lamivudine (3TC) (Epivir) --Third-line agent; high rates of resistance
What is wrong with the antivirals given for HBV? (besides interferon alfa)
Pts who take these antivirals can have severe rxns if they are coinfected with HIV
if you want to take a pt off antivirals for Hep B what do you need to assure?
1) these pts should not have cirrhosis (if they have cirrhosis they should still be on meds)
2) follow pt long term
3) evidence of HbeAg loss and seroconversion to anti-hie after 1 yr of treatment
4) persistently normal ATL levels
5) persistently undectable HBV DNA
is lifelong therapy required/common for HBV?
lifelong therapy is common–
Lifelong therapy is required if patient has cirrhosis (risk of reactivation is high)
know HBV who flow chart
slide 16
Hep C is caused by:
symptoms:
Large or repeated exposures to infected blood (Ex: an entire organ, pints of blood, constantly sharing needles with someone who is infected (takes quite a bit to get you infected—not just 1x)
Symptoms common to all viral hepatitis infections
in Hep C, the virus can live outside of the body for
4 days
Hep C blood tests?
- Anti-HCV antibodies—it just tells us that you are infected
- Presence of viral RNA
Can Hep C become chronic?
yes it can
Which is most common, Hep A, B,C?
C
is sexual contact an issue with hep C
no –that is an issue for Hep B
think needle stick, IV drug use
can Hep C be vertically transmitted?
yes
what % of Hep C pts will clear it without any tx?
therefore what % of Hep C pts will become chronically infected?
15-25%- clear it
so 75-85% will become chronically infected
of the 75%-85% of Hep C pts that will become chronically infected, what % will develop liver disease?
70%
of that 70% that develop liver disease from chronic infection of Hep C, what % will develop cirrhosis?
5-20%
What is the leading cause of liver transplants in the US?
Hep C
to Tx Hep C, you need to know the _____ of the pt
explain
genotype
Genotype 1 – historically difficult to treat
Genotypes 2, 3 – decent response rate
Genotypes 4, 5, 6 – difficult to treat
All drugs to tx Hep C are used in _______
so therefore you need to know if:
combinations
Need to know: =Genotype =Presence and degree of cirrhosis =Treatment naïve? Like if the person that infected your patient has had treatment you need to know because the new patient could have resistance
Tx goal for Hep C
99% of pts will achieve
- Achieving SVR12 (Sustained virologic response by 12 weeks)
- Virologic response means that the hepatitis C virus is not detected in the blood during treatment. When the virus continues to be undetectable 12 weeks or more after completing treatment, a “sustained” virologic response (SVR) has been achieved.
- Reversal of inflammation and fibrosis
- Decreased mortality by 60%
99% will achieve SVR24
should all Hep C patients receive antiviral tx?
all except those with a life expectancy < 12 months due to non-liver comorbidity
ex: ex: someone with pancreatic cancer with a 6mos window, we will not treat them for hep C.
is Hep C tx okay for pregnancy women?
no not recommended
Why is it important for pt compliance for Hep C?
If patients are not willing/able to comply they SHOULD not receive antiviral tx. why??
Patient must be willing and able to complete therapy (consider cost, access, and mental illness)
If they only take part of it, they can develop a resistant strain and then if they pass it to someone else, they can have resistance and its now harder and harder to tx.
Is there a postexposure prophylaxis for HCV exposure
nope
What type of meds do you give for HCV
Acute treatment (within first 6 months of infection) is the same as chronic treatment, except interferon is an option for this group
HCV tx used to be interferon but now we use ______ why?
new all oral tx because they have similar efficacy across populations whereas interferon did not work very well in African Americans/Latinos
Higher degree of _______ is correlated with poorer response rates for HCV tx.
fibrosis to the liver
the more fibrosis in your liver, the more damaged it is, and the worse the outcome
for these patients:
Use longer duration
Add ribavirin
**assess degree of fibrosis of liver before giving tx
does Prior treatment failure decrease chance of response with a different regimen?
nope
RIbavirin (Copegus, Rebetol, Ribasphere, Moderiba)
what is it?
drug used for?
how to use it?
HCV
it is an RNA polymerase inhibitor
Always Used in combination with other HCV regimens; NOT monotherapy (always see it in conjunction with something else)
Adverse affects of ribavirin
- Hemolytic anemia
- Teratogenic (category X) – documented negative pregnancy test required prior to treatment
ribavirin is contraindicated in what types of patients
Contraindicted in women who are pregnant, and contraindicated in men who are trying to have kids
Avoid this drug 6mos before you become pregnant & same with the male partner
Need a documented pregnancy test
Need to prove that you use 2 reliable forms of BC
ribavirin has interactions with what other drugs?
Major drug interactions seen with didanosine and azathioprine
Simeprevir (Olysio) is a drug to tx?
adverse effects?
metabolized by
cheap? expensive?
Hep C
it is a HCV protease inhibitor
Adverse effects Photosensitivity reaction (going out in sun you may develop a skin rxn or rash)
Metabolized by CYP3A4
So lots of drug interactions
insanely expensive
Lepidasvir/Sofosbuvir (Harvoni) used to tx?
important characteristics?
this drug is a combo of 2 drugs
-tx of Hep C
-Contraindicated in moderate to severe hepatic impairment
-Antacids decrease efficacy of lepidasvir – separate by 4 hours (so don’t take them within 4 hours of eachother)
very expensive
all the hep C drugs are
- very expensive and very recent
- a lot of them react with CYP3A4
- if they come in a pack it is better compliance
for a long time we went with no tx and then after 2013 we got a bunch of drugs
Ombitasvir/Paritaprevir/Ritonavir (Technivie)
these tx
–> characteristic
inhibit CYP3A4
Hep C and come in a pack so good for compliance
Elbasvir/Grazoprevir (Zepatier)
tx for?
important because
Hep C
very recent—Lugo uses this the most
can be taken with ribavirin
Acid production occurs in ________ located in the body and fundus of the stomach. They contain receptors for:
parietal cells
receptors for
- gastrin
- Acetylcholine
- histamine
gastrin, Ach and histamine work together to create stomach acid. They are Tightly joined so they potentiate each other—what does this mean?
so the response to 2 of them is greater than 1
So if you have all 3 together= you get a t stomach acid
If gastrin is impaired you get from ach and histamine and not quite as much stomach acid
when creating stomach acid
where do gastrin, acetylcholine, and histamine come from?
Ach
-vagal stimulation of postganglionic enteric neurons
gastrin
-from the G cells
histamine
- ECL (enterochromaffin-like) cells
- histamine gets released in response to act and gastrin
Food in stomach (once it gets absorbed into blood) it starts to stimulate the process of ______
which causes
releasing Ach, Gastrin and Histamine
them to bind to parietal cell and that triggers the release of H+ ions into lumen which helps you make stomach acid
stimulation of gastrin release
dietary peptides/eating
why shouldn’t you use anticholinergics to tx stomach acid?
anticholinergics (decreases acetylcholine) –Bad idea just to lower acidity because greater systemic effects. Theyd get super dried out and constipated and tired, cognitive impairment
what do we use to tx Acid/Peptic Disease?
Antacids
H2 receptor agonists
proton pump inhibitors
Mucosal Protective Agents
Antacids–used to tx
examples of antacids
Acid/peptic Disease
- Sodium Bicarb
- Calcium bicarb
- magnesium hydroxide/aluminum hydroxide
Antacid: Sodium bicarbonate (baking soda, Alka Seltzer)
produces ________which leads to
issues with using sodium bicarb?
CO2 which leads to gastric distention and belching
Issues with sodium: patients with renal disease, HTN, heart failure
NaCl formation may be an issue for patients with hypertension, renal insufficiency, heart failure Metabolic alkalosis (known as milk-alkali syndrome)
Antacid:
Calcium carbonate (Tums)
produces ______
issues with using it?
CO2?
Belching/bloating/constipation Hypercalcemia Milk-alkali syndrome Minimal renal excretion Neutralizes acid but it doesn’t break down well in the gut
Antacids:
Magnesium hydroxide/aluminum hydroxide (Maalox, Mylanta
issues with using it
no gas generated, but can lead to
magnesium- diarrhea
aluminum-constipation
*Metabolic alkalosis is not a concern
Renally excreted
If a patient is taking an antacid and is having difficulty controlling the symptoms, do you increase the frequency or the dose?
increase the frequency
because if you take 2 tums, it can neutralize all of stomach acid so don’t need MORE but need a continuous dose for when it resurfaces
What is a general problem with using antacids very regularly?
You are majorly decreasing your stomach acid, and you NEED that stomach acid. By continuously decreasing your stomach acid, you can really impair your ability to absorb all kinds of things (protein, carbs, fat, vitamins, folate, minerals, etc.
this is not just for antacids–anything that Constantly decreases your stomach acid is not a good thing. You need stomach acid to break down things in your diet and without stomach acid its not going to happen
H2 receptor antagonists
-what are they?
name some examples
end with the word
Histamine 2 receptor blocker. They block histamine from binding to its receptor (mimic structure of histamine).
Histamine 2 is for acid/peptic disease (histamine 1 is for allergic response)
Cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid)
“dines”
Duration of action for H2 receptor antagonists Cimetidine vs NIzadatine vs. Ranitidine vs. Famotidine
longest duration of action: **Famotidine (most potent and most selective) 10-12h
Really easy to use (kids and adults) available IV and oral and lasts a long time and don’t have to take it all the time. Can get OTC
-Nizatidine 10h
-Ranitidine 6-8h
shortest duration of action =**Cimetidine (least potent) 4-5h (Least potent and doesn’t last very long and has tons of drug interactions )
H2 receptors antagonists
effect on elderly
or those with renal disease
Elderly have 50% clearance and ↓ Vd (the drug builds up in elderly people and can become toxic)
Severe renal impairment requires dose adjsutment
H2 receptor antagonists
how do they work? (dynamics)
effect?
- Highly selective for H2 and do not affect H1 or H3
- Competitive inhibitors of parietal cell H2 receptor
Mechanism
Directly compete with histamine binding at parietal cell
Once bound, decreases effectiveness of ACh and gastrin binding
-Decreases volume of gastric secretion as well as concentration of pepsin
H2 receptor antagonists have better control during the day or at night? (nocturnal)
Excellent control of nocturnal acid secretion with modest effect on meal-stimulated secretion
–>They do a good job of supressing acid secretion while you are sleeping—but not as good of a job when awake.
This is because histamine is responsible for nocturnal acid secretion while meal-stimulated secretion is due to mainly to ACh and gastrin
H2 receptor antagonists are often give how many times a day?
Often given BID because duration of action is 12hrs.
H2 receptor antagonists
-safe/dangerous?
very safe
but you have to remember that you are stills suppressing stomach acid (which can be bad over a long period of time in terms of absorbing vitamins/minerals/protein/carbs)
H2-Receptor Antagonists
adverse effects
-IV form of drug appears to cause mental status changes in some groups: Pts with Renal disease, hepatic dysfxn, elderly
-General side effects
Diarrhea, headache, fatigue, constipation
Cimetidine is a special H2-receptor antagonist. Why?
overall good or bad choice in tx of stomach acid?
1) it’s the least potent and has a ton of drug interactions (Inhibits CYP1A2, 2C19, 2D6, 3A4)
2) it’s OTC so people can just take it and think its safe
3) interacts with warfarin
4) Long termuse or very high dose can lead to gynecomastia or galactorrhea
5) If you have muluscum contegiosum (in teenagers) can be used to tx
But otherwise it’s a very bad choice in tx of stomach acid
PPIs
what do they stand for
what do they tx?
name some
-Proton Pump Inhibitors
-Acid-Peptic Disease
-Omeprazole (Prilosec)
Esomeprazole (Nexium)
Lansoprazole (Prevacid)
Dexlansoprazole (Dexilant)
Rabeprazole (Aciphex)
Pantoprazole (Protonix)
PPI meds end with the word ______
prazole
What is the difference between omeprazole and esomeprazole
esomeprazole is the same as omeprazole but it’s the pure isomer so it’s the active isomer of omeprazole
All PPI’s are _______ drugs that are very sensitive to
what does this mean?
prodrugs , sensitive to degradation by acid
- PPIs are not active in their initial form (has to be activated)
- Because they need to be activated, the pts liver must be working well
–> If we drop them in acid, they are destroyed on contact so they are coated in acid resistant capsule or something
–>Capsules have pellets in them so you can open it up and pour it into drink and mix it because the pellets are also acid resistant (coated)
come in the form of Delayed release acid-resistant capsules or enteric-coated tablets
How does a PPI work?
What is something very important to remember about giving a PPI? It must be:
- ->Active drug irreversibly binds H+/K+-ATPase
- ***Bioavailability decreased by 50% if given with food
1) You cannot take them on a full stomach/given with food
2) You have to eat AFTER you take these (or else they don’t work)
Why do you have to take a PPI on an empty stomach?
when should you take a PPI vs. eat?
you should take a PPI 1 hr before a meal.
–> Proton pumps are only active when there is food (because food activates release of stomach acid)
So in order for drug to bind to it’s receptor site, the pump has to be acively working
so you give the drug, let it get metabolized/in circulation, then you eat an hour later. Once you eat, the pump opens because it senses food, and the drug binds to pump and stays
Once a PPI binds to a proton pump, what happens to the pump?
it becomes deactivated and “destroyed” so no acid is being created
the body will generate a new pump over the next 18 hrs
For PPIs does duration of effect correspond to T1/2?
NO
t1/2 is 1-5 hours yet they are dosed once a day (short half life)–but the effect is very long because it destroys a proton pump
Full efficacy of PPIs is not seen for ____ days. why?
3
- -> 70% of your pumps become active after the first time you eat for the day
- -> 20% of your pumps get synthesized over 24hr period
So its hard to capture all pumps that are working so full efficacy cannot be seen for 3 days because its hard to nab all of these pumps—may be able to get majority but it takes awhile
PPIs are mainly metabolized in the _____using what pathways?
this means we do not need to dose adjust for
liver (so if SEVERE liver failure we need to dose adjust)
CYP3A4 & 2C19
renal impairment (because negligible renal excretion)
Why is 2C19 involvement in PPIs a problem?
asians are not very effected by PPIs because they don’t have 2C19
there are IV formulations for esomeprazole and pantoprazole if pt is in hospital
how does that work if pt has to eat?
continuous drip. You have a little bit of proton pumps working all the time, so over time we’re getting the few that are working all the time.
Which is better for supressing acid secretion throughout the day vs. night?
day- PPI
night- H2 receptor antagonist
*Don’t give people PPI for nocturnal acid secretion—just give them H2 blocker
Are all PPIs equally protective if using equivalent doses?
yes (although this is not Lugo’s experience)
if one doesn’t work as well, switch them to another
Where on the proton pump do PPIs work?
Inhibit both basal and stimulated acid secretion (block the final step prior to H+ release)
Right before H+ is released, that’s where they are working (in that area of proton pump)
PPIs adverse effects
1) small % of patients get diarrhea, headache, stomach pain (may need to switch them to H2 just based on severe pain)
2) B12 and calcium deficiency with long term use
3) Infections
- increased risk for nosocomial pneumonia (hospital pneumonia)
- increased risk for Cdiff. (gastric acid helps fight off infection so when you don’t have much, it is easier to get infection
If pt acquires Cdiff while on PPIs you should
take them off the PPIs
PPIs
drug interactions
Rare since half-life is so short (doesn’t have time to rxt with a ton of stuff) –not a lot of drug interactions overall
- however drugs that need stomach acid to work won’t work as well (because you are decreasing your stomach acid with PPIs)
PPIs and clopidogrel
what is clopidogrel?
what is the issue with it and PPI?
Clopidogrel (Plavix) decreases platelet aggregation in people who have had a stroke, MI, recent CABG, and stent placement. It is a prodrug that requires CYP2C19 to be converted to its active form.
some PPIs use 2C19. so these drugs would compete in body for 2C19.
therefore PPIs have been shown to decrease conversion of clopidogrel to its active form.
What can you give pt that is taking clopidogrel but needs a PPI?
Rabeprazole or Pantoprazole in patients on clopidogrel and only if absolutely necessary. (these 2 do not rxt with copidogrel)
Muscosal Protective Agents are used to tx
Acid/Peptic disease–
Mucosal Protective Agents Sucralfate (Carafate) -used to tx -how does it work -when do you administer? -side effects? -problems?
specifically ulcers an erosion
Binds selectively to ulcers and erosions (like a bandage)
Administered on an empty stomach 1 hour before food
Empty stomach because we want it to adhere to what its supposed to
Virtually no side effects (becaues its not absorbed—it just stays in GI tract)
(can rxt with other drugs though)
problem: you have to give it 4x a day and on an empty stomach so compliance is not good
Mucosal Protective Agents Misoprostol** stimulate prostaglandins -acid suppressant? -Stimulates \_\_\_\_\_\_\_&\_\_\_\_\_\_\_ secretion because of its stimulation \_\_\_\_\_\_\_\_; which then increases mucosal blood flow -how often to admin?
-not an acid suppressant it just forms a mucosal barrier
(although it modestly suppress acid)
- mucus and bicarbonate, prostaglandins
- 3-4x a day (like sucralfate)
Misoprostol
- excreted how?
- why do you give this drug with NSAIDs?
- adverse effects in general?
- drug interactions?
- Excreted renally but does not require dose adjustment in impairment
- Used in long term NSAID therapy as a protectant (protects stomach from NSAIDS)
- GI issues are a big problem with these agents (diarrhea, cramping)
- none
Misoprostol/pregnant women
NO NO NO
It has been used to induce abortion—do not use in pregnancy
Bismuth Subsalicylate (Pepto-bismol)
- which part is absorbed?
- what does it do?
- what does it tx?
- Bismuth part is not absorbed; salicylate part can be absorbed and renally excreted
- Coats erosions and ulcers (but does not adhere like sucralfate. Carafate/sucralfate is like a bandage—this is not. It just kind of coats it.)
- Peptic Acid Disease as a Mucosal Protective Agent
Bismuth Subsalicylate
what else can it do besides tx peptic acid disease
Decreases stool frequency and liquidity in acute infectious diarrhea (unique niche in GI healthcare OTC)
Antimicrobial effects of bismuth beneficial in H. pylori infection and traveler’s diarrhea
Bismuth Subsalicylate adverse effects
- Blackening of the stool; darkening of the tongue if taking it more than once
- High doses over long periods could cause salicylate toxicity –don’t OD on this
Caution in renal impairment
can you give bismuth salicylate to kids?
–no. Do not give this to kids
There is a specific children’s Pepto-Bismol with different active ingredient
GERD stands for
Someone has GERD if:
how to tx
Gastroesophageal reflux disease
having symptoms 3 or less times a week
use antacid or H2-blocker prn (as needed)
in GERD, what is superior? PPI or H2?
PPI
when treating GERD with PPI, recurrence of GERD 6 months after discontinuation of PPI ___%
how to help this situation?
80%
So you don’t want pt on PPI indefinitely so you need to look at their lifestyle while they are on the meds.
Changing their lifestyle/checking their other meds could help alleviate these symptoms—treat the underlying cause
Patients with severe symptoms from GERD (asthma, chronic cough, laryngitis, noncardiac chest pain) should use what tx and for how long?
PPI BID 3mos.
Peptic Ulcer Disease (PUD)
what is it?
how is it different from GERD
not just GERD—we have an ulcer and its been identified
ulcer- A sore that develops on the lining of the esophagus, stomach, or small intestine.
for PUD do we use PPIs or H2?
PPIs are superior –> drug of choice for rapid healing
(90% of duodenal ulcers in were healed 4 weeks, gastric ulcers healed in 6-8 weeks
Then once body recovers, we need to make sure we can take care of that rebound acid ( so taper)
however H2 receptor antagonists provide nocturnal coverage which helps with healing
How do we tx ulcers caused by NSAIDs?
Discontinue NSAID if possible; if not, use PPI for more reliable acid suppression
PPIs used qd for prophylaxis against NSAID induced ulcers
How do we tx H. Pylori ulceration?
**Only PPI (in combination with antibiotics) is effective to treat ulcers and eradicate the bacteria
(Treats as well as eradicates)
If H. pylori cannot be fully eradicated, use H2-blocker qhs (everynight indefinitely) to prevent ulcer recurrence
Pt has H. Pylori and its not going away but we still need to prevent the ulcer so we use an H2 blocker
How to tx a rebleeding ulcer?
Goal is to maintain pH above 6 for 3-5 days to facilitate clotting
Use either really High dose PPI or continuous IV
Stress Ulcer Prophylaxis in Critically Ill
what do we use to tx?
exception:
H2-blockers preferred IV due to cost and proven efficacy
Exception: if pt has NG tube, use immediate release oral omeprazole (Zegerid)
–>Must be given continuously for best suppression in this patient population
How to tx a pt with H. Pylori w/ acid disease
Only treat pts with a positive test result
FDA approved regimens:
Lots of different regimens to give to reduce acid. Then we are also going to give some kind of antibiotic to tx H. Pylori.
There are a lot of different products/combos to give
Every regimen is: 2 antibiotics and something for stomach acid (usually PPI or H2)
***Almost all regimens are Some kind of PPI, + clarithromycin + amoxicillin
One weird regimen= bismuth and H2 blocker (to make up for fact that we don’t have PPI if someone is allergic etc), + metronidazole, + tetracycline
