bennett exam 3 objectives + answers + candy

compare and contrast protective and destructive GI factors

protective: gastric mucus, bicarbonate, and prostaglandins (stimulate secretion of mucus and bicarb)

destructive: gastrin (stimulates acid secretion), ACh (stimulates release of gastrin), histamine (stimulates proton pump), pepsinogen (breaks down GI lining)

what are the possible pharmacological interventions for GERD

increase lower esophageal sphincter pressure (prevents acid from going up)

enhance esophageal acid clearance

improve gastric emptying

protect esophageal mucosa

decrease gastric volume of refluctate

prevent complications

what are the possible treatments for GERD

antacids (neutralize gastric acid)

H2RAs (block stimulation of proton pump)

PPIs (block proton pump)

prokinetics (increase LES pressure)

mucosal protectants (create a protective barrier)

what is the mechanism of action of antacids

weak base that reacts with HCl to form salt and water → neutralize acid, increase pH, and inactivate pepsin

what are the ADRs for antacids

N/V/D, acid base imbalance, fluid retention (due to Na+ containing products)

what are the advantages to using antacids

symptomatic relief of mild GERD

can be used with other acid suppressing drugs

rapid onset of action (minutes)

what are the disadvantages of using antacids

should only be used short-term

need frequent dosing due to short DOA

most products contain Na+

how/when should antacids be taken to avoid interactions with other drugs

separate from other drugs by 2-4 hours to minimize absorption issues

what component of antacids can cause diarrhea

Mg2+

what component of antacids can cause constipation

Al3+ and Ca2+

what does acid neutralizing capacity mean

measure of how much stomach acid a specific dose of antacid can neutralize to a pH of 3.5

what is simethicone

antiflatulent that reduces surface tension of air bubbles in the GI tract

what is the mechanism of action of H2 receptor antagonists

block H2 receptors → decreased stimulation of proton pump by histamine

rank the various H2RAs from most to least potent

famotidine (Pepcid) > nizatidine > cimetidine (Tagamet)

what is the advantage of using H2RA therapy

effective in decreasing nocturnal acid secretion

what are the ADRs of cimetidine

gynecomastia or impotence in men, galactorrhea in women, worsening of dementia/confusion in elderly patients

what enzymes does cimetidine inhibit

CYP1A2, CYP2C9, CYP2D6, and CYP3A4

how are PPIs usually formulated

delayed-release or enteric coated prodrugs

what is the mechanism of PPIs

irreversibly binds the H/K ATPase pump on parietal cells

how are PPIs activated

weak bases activated by the acidic environment in the parietal cells

what are DDIs with PPIs

CYP2C19 inhibitor, should also avoid clopidogrel

what are the advantages of using PPIs

superior to H2RAs

inhibits fasting and meal stimulated acid secretion

longer effects

what are the disadvantages of using PPIs

hypergastrinemia is more frequent/severe

rebound hypersecretion after discontinuation

increasing pH means increasing risk of bacterial infections

what are the ADRs of PPIs

osteoporosis/bone fractures, B12 deficiency with use >1 year

what is the mechanism of metoclopramide (Reglan)

dopamine receptor antagonist → increases LES pressure and increases ACh

what are some characteristics of metoclopramide

use with caution in patients with parkinson’s disease

use with caution in renal impairment

interacts with levodopa (parkinson’s drug)

undergoes hepatic metabolism

passes BBB and placenta

should decrease the dose in renal dysfunction

what are some ADRs of metoclopramide

hyperprolactinemia, extrapyramidal syndrome, dizziness

what drugs are mucosal protectants

sucralafate (carafate), bismuth subsalicylalte (pepto), misoprostol (cytotec)

what is the mechanism of sucralafate

forms paste in acidic solution that has a negative charge that binds to the positive charged proteins in ulcers → physical protective barrier

also stimulates bicarb and PG secretion

what is an ADR for sucralafate

constipation

how is sucralafate dosed

four times a day

what is the mechanism of misoprostol

PGE1 analog — binds PG receptor on parietal cell → decreases histamine and gastric acid, maintains mucosal blood flow, and increases mucus and bicarb secretion

what are the ADRs for misoprostol

diarrhea and abdominal cramping

what pregnancy category is misoprostol

category X

what is the mechanism of bismuth subsalicylate

absorbs toxins, stimulates PG/mucus/bicarb secretion, coats ulcers, and protects against gastric acid and pepsin

what pregnancy category is bismuth subsalicylate

category C/D

what are the DDIs for bismuth subsalicylate

decreased tetracycline absorption, increased effects of aspirin/warfarin/oral glycemic drugs

why should use of NSAIDs be minimized to protect the GI

acidic drugs that can cause ulcers, compromise mucosal integrity, and damage the lining of the GI tract

also inhibit PGE1 synthesis (PG is protective factor)

what are antiemetics

dugs that are effective against nausea and vomiting

what receptor is ondansetron specific for

5HT3 only

what receptor is promethazine specific for

dopamine, histamine, and muscarinic receptors

what receptor is metoclopramide specific for

dopamine and some 5HT3 receptors

what is the mechanism for ondansetron (zofran) and polanosetron (aloxi)

block 5HT3 receptors in vomiting center of the GI tract and the CTZ

what type of drug is ondansetron

prototype — first drug of its class and what every other drug is based off/tested against

how can ondansetron be given

PO or IV

is ondansetron or palosetron more potent

palosetron

what is a serious ADR for -setron drugs

QT prolongation

when are -setrons given for CINV

before chemo or continuing 3-5 days following chemo

how are -setron drugs metabolized

hepatically

how are -setron drugs eliminated

renally and hepatically

which -setron drug requires dose adjustment in hepatic dysfunction

ondansetron

how are -setron drugs dosed for CINV

once daily

what drugs are dopamine antagonists

domperidone, droperidol, haloperidol, chlorpromazine, metoclopramide, prochlorperazine, and promethazine

where do dopamine antagonists work to treat emesis

dopamine receptors in the brain and CTZ

what are the ADRs for dopamine antagonists

EPS/dystonia, sedation, galactorrhea, breast tenderness, acute EPS in children

what is the antidote for acute EPS in children

Benadryl or benztropine

which dopamine antagonist has antihistamine properties

promethazine (phenergan)

which dopamine antagonists can cause QT prolongation

droperidol and promethazine

which dopamine antagonists are used as anti-psychotics

haloperidol, chlorpromazine, and prochlorperazine

what dopamine antagonist is selective for dopamine receptor subtypes 2 and 3

amisulpride (barhemsys)

what is the mechanism of substance P/NK1 antagonists

inhibits substance P and NK1 receptors that control the emetic reflex in the medulla

what drugs are substance P/NK1 antagonists

aprepitant, rolapint, netupitant, fosaprepitant

what are substance P/NK1 antagonists used for

delayed onset of N/V

N/V due to cisplatin

in combo with Zofran and steroids to treat delayed CINV

what are DDIs for substance P/NK1 antagonists

drugs metabolized by CYP3A4 or 2D6 (rolapitant) — dexamethasone, warfarin, oral contraceptives

what is the mechanism of cannabinoids

possibly activates CB1 neurons and the CTZ

what are ADRs of cannabinoids

hallucinations, euphoria

what are cannabinoids used for

CINV when unresponsive to other treatment

appetite stimulant

what are the metabolite characteristics of cannabinoids

highly protein bound, excreted slowly in feces and urine

what are examples of cannabinoids

dronabinol, nabilone, sativex (only in canada and UK)

what properties of benzodiazepines are effective in treating CINV

anxiolytic, sedative, and amnesic properties are beneficial to treat anticipatory CINV

what two benzodiazepines are commonly used for anticipatory CINV

midazolam and lorazepam

what are some ADRs of benzodiazepines

dependence, sedation, and anterograde amnesia

what is the mechanism of dexamethasone

suppresses inflammation and PG production in cancer cells

what are the advantages of dexamethasone

euphoria, appetite stimulant

when should dexamethasone NOT be used

for simple nausea

what are the ADRs of dexamethasone

cushings syndrome, hypertension

what are the three types of CINV

anticipatory, delayed, and acute

what drugs/drug classes are used as anti-diarrheals

anti-motility drugs, opioids (Lomotil, Imodium, Viberzi), somatostatin analogs (Octreotide), anti-secretory drugs (Bismuth), 5HT3 antagonist (alosetron)

what drugs/drug classes can be used as laxatives

hydrophilic colloids (metamucil), ammonium detoxicants (Lactulose, Enulose), stool softener (docusate), cathartics (bisacodyl), 5HT4 agonists (tegaserod and prucalopride), prostone analogs (amitiza), opioid antagonists, guanyl cyclase agonists, NHE3 inhibitors (tenapanor)

what is the generic name for Lomotil

diphenoxylate + atropine

describe the two components of Lomotil

diphenoxylate — opioid agonist

atropine — anticholinergic to reduce risk of abuse

what is the mechanism of Lomotil

binds mu and delta opioid receptors in GI tract to alter motility and secretion → decrease loss of fluid and electrolytes

why is Lomotil not used for pain

it poorly penetrates the CNS

what are the ADRs for lomotil

constipation and anticholinergic effects

what pregnancy category is lomotil

category C

what is the mechanism of Viberzi

mu opioid agonist and delta opioid antagonist

what are the ADRs for viberzi

constipation, nausea, increased LFTs, URTI, and increased risk of MI

what is Viberzi used for

IBS-D

what are contraindications for Viberzi

alcoholism, hepatic impairment, GI obstruction, pancreatitis

what is the mechanism of octreotide

somatostatin analog — inhibits gastric acid, pepsinogen, intestinal fluid, and bicarb secretion

what is octreotide used for

acromegaly, metastatic carcinoids, severe diarrhea, VIPomas (tumor), profuse water diarrhea, AIDS related diarrhea, GI bleeding

what are the ADRs of octreotide

diarrhea, abdominal discomfort

compare methyl naltrexone, alvimopan, and naloxegol

all are opioid antagonists that are used to treat constipation

contrast methyl naltrexone, alvimopan, and naloxegol

methyl naltrexone — does not pass BBB, no CNS effects, for opioid induced constipation, D/C all other laxatives

alvimopan — contraindicated for opioid use >7 days before using drug, max of 15 doses, for post-op bowel movements, increased risk of MI

naloxegol — don’t take with grapefruit juice, CYP3A4 inhibitor, D/C all other laxatives unless sub-optimal therapy after a few days

what is the mechanism of tegaserod

5HT4 agonist — increases release of ACh and NO, increases intestinal and chloride secretion from colon → increase stool liquidity

what are the ADRs for tegaserod

diarrhea, MI, stroke, and unstable angina

what is a warning for use of tegaserod

suicidal ideation

potentiating serotonin

how and why is tegaserod restricted

restricted due to possibility of MI, stroke, and unstable angina — only use if there is no satisfactory response to any other treatment

what is tegaserod used for

short-term for women with IBS-C who have no responded to other treatment, chronic idiopathic constipation

what is the mechanism of lubiprostone (amitiza)

prostone analog — activates type 2 chloride channels → chloride rich fluid secretion → soften stool, increase motility, and promote spontaneous bowel movements