DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes

Things to keep in mind:

- Gerd: Dosing of ppi’s and h2’s she pointed out, potential ADE and mechanism of action of all those drugs , know the when to tx a pt w/ various comorbidities ex: pt is HP w/ penicillin, what would you give them?
Pt w/ active ulcer vs occasional gerd sxs – know when to use PPI vs fomedidine.
- Constipation: when to pick an appropriate regimen of laxatives for a pt – it’ll be an obviously wrong dose of qhrs or qd etc. what drugs can induce constipation?
- IBS/D: pick out medications of what are not indicative (like a laxative when a pt swings back and forth) ADE of medications we talked about; common ade, what medications you wouldn’t use, CI
- Diarrhea: when is it appropriate to tx – ADE, n/v: ade, moa, pick most reasonable medication like ex: benzo’s are best for anticipatory medication.

Acidic-Peptic disease
● GERD tx goals: alleviate/eliminate Sx. Decr reflux frequency, recurrence & duration→ promote injured mucosal healing & prevent complication development.
o Therapy target: incr LES pressure, enhance esophageal acid clearance, improve gastric emptying, protect esophageal mucosa, ↓refluxate acidity & gastric vol
o Phase I = lifestyle mod (elevate head, avoid EtOH & smoking), dietary changes (avoid food irritants, incr food frequency), wt reduction, avoid drugs that worsen GERD (Iron, estrogen, NSAIDs…), OTC H2 receptor
antagonist/antacids
o Phase II = acid-suppressing therapy→ H2RA, PPI (start w/ severe sxs). 70-90% will relapse in 1 yr after d/c, maybe long term therapy → relapse/comp
o Lower doses w/ less severe, higher w/ ↑severity (Worry about Barrett’s esophagus, strictures, or hemorrhage)
● ZES tx goals: control hypersecretion of acid. Locate & possibly reduce gastrinoma, surgical option, med management = limit comp. but not curative
● PUD tx goals: etiology dependent – relieve pain, heal ulcer, prevent recurrence & reduce complications.
o Eliminate/reduce irritants- NSAIDs (if can’t d/c, admin w/ PPI or H2RA), eradicate H. pylori. PPI provide more rapid sx & faster ulcer healing → surgery is the best option
o W/ NSAIDS reduce dose or use APAP, Nonacetylated salicylates or selective cox 2 inhibitors
o Prevent rebleeding →high/continuous dosing of IV PPI x 3-5d (reduces bleeding); intragastric pH>6 ↑ coagulation & plt aggregation
● HP tx: Resistance at low pH d/t multiplication & activity = limited; higher pH= higher response w/ Abx ➔ ie why H2 aren’t useful d/t not being able to raise pH. Tx for 2 wks
DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes
Drugs that reduce intragastric acidity – Most commonly used drugs
PPI Irreversibly binds to H/K ATPase, an ● Most efficacious to take DOC for HP infxn bc it can Generally well tol: All preg B, except O = C, Protects itself w/ enteric
Omeprazole (Prilosec) enzyme that transports acid across 30 mins – 1 hr BEFORE meal (15-30 raise pH to 6 at higher ● HA, breast feeding unknown coating from HCl→weak
Lansoprazole (Prevacid) the gastric parietal cell. mins pre breakfast, 10-12 hrs apart doses! dizziness, antacids/alkaline may
Pantoprazole (Protonix) - @ therapeutic dose, inhibits prior to meal/snak if BID) Quad therapy x 2wks somnolence, N/D, DDI → know there aren’t break enteric coat
Esomeprazole (Nexium) >90% of 24 hr gastric acid ● P,E,L = short ½ life → IV x 1. PPI BID constipation. many DDI’s &
secretion 24-48 hrs 2. 3 Abx: ● Possible ↑ ketoconazole/warfarin
Others: Rabeprazole, Maintain pH>4 post prandial ● L – disintegrating tab a. Clarithro, Amox, risk of MI → interact w/ everything *Asian pop. = 4 x ↑ in
dexalnsoprazole ● Pantoprazole also Metronidazole BID: dysregulation of - Affect drug absorption median omeprazole
(dexilant) metabolized by sulfphotransferase: for no bismuth s/e vascular NO synthesis where acid/base exposure, may need to
less DDI Those w/ penicillin or ● ↑ risk of hip environment is ↓dose and clopidogrel
● P&R = coated ● Dosing for GERD: mycin allergies: Bismuth, fx w/ long term use required (↓azole, ↑ interaction
tabs o O: 20-40 mg/d x 4-8wks metro, tetra – QID w/ or multi dose digoxin)
● O,E,L = coated o P: 40 mg/d x 8 wks bismuth s/e ● Vit B12 - CYP2C19&3A4 enzyme
caps – can be opened deficiency – ↓ serum levels
and mixed ↓ ulcer incidence & ● Resp&enter (diazepam, PHT,
● P, L, E = IV Dosing ranges come 20’s & 40’s – complications in pts ic infxn – c.diff, CAP, warfarin w/
● O = NG/ND keep in mind for testing purposes continuing aspirin or nosocomial Omeprazole)
tubes NSAIDs pneumonia - ↓Ca absorption or
inhibit osteoclast fxn
Other uses: - Weak antacids or
DU,GU, GERD, EE, ZES, HP, alkaline juice → break
SRMD enteric coat
H2-receptor antagonists - H2RA competitively & selectively Dose for GERD GERD, DU/GU, Prevention Generally safe, ADE is DDI: Pt w/ overnt sx or no
(H2RA) inhibit histamine action on H2 - Ranitidine: 150 mg BID of stress related bleeding LOW (except - Cimetidine complications may
- Cimetidine (Tagamet) – receptors on parietal cells = reduce - Famotidine: 20 mg BID - SRMD cimetidine) PHT, Warfarin, benefit best from H2RA
Don’t use d/t high DDI basal & stimulated gastric acid GI: D, constipation theophylline, nifedipine,
- Ranitidine (Zantac) secretion Will have to dose reduce for poor Thrombocytopenia: benzos, carbamazepine,
1
 DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes
- Nizatidine (Axid) - SSS - Histamine bind to H2-receptors → CrCl <50 in Ranitidine, <20 in reversible BB, quinidine, TCA,
- Famotidine (Pepcid): activate adenylate cyclase → ↑ Nizatidine, <10 in Famotidine CNS: mental confusion, verapamil → just know
most widely used for intracellular cyclic AMP → activate HA, dizziness, you shouldn’t use it
SRMD parietal cell proton pump to Cimetidine&Ranitidine (less): CYP450 drowsiness (high dose - Ranitidine < cimetidine
secrete hydrogen ions against a metabolism w/ elderly/ICU – adj - C&R inhibit renal tubule
concentration gradient in exchange renal dose!) secretion of
for K ions Ranitidine: procainamide – dose
- H1 = no significant action → does Hepatotoxicity: rare dependent → not seen
not block H2 receptors Famotidine: HA w/ famotidine
Cimetidine: - Azoles – incr pH =
gynecomastia, reduce absorption of
impotence HR2A
Rare: Arrhythmias,
angioedema, derm rxn
(rash)
Antacids Neutralize/buffer existing HCl Onset: 5-15 mins, last ~2hrs - GU/DU – pain relief - Mg2+:diarrhea Avoid PO meds w/in 1-2 Mixing Mg + HCl sets off
- Al: AlOH Weak base + HCL = salt + H2O - Food elevated pH to 5x & prolongs - GERD sx - Al 3+: constipation, hrs➔ reduce drug the CO2 ↑ flatulence →
- Ca: CO3-Tums ↑ LES pressure antacid effects x 2 hrs - SRMD insoluble salts w/ absorption use Simethicone
- Magaldarte - AlMg ↓intragastric acidity →↑ pH - Antacids cleared from empty - Adjunct: ZES dietary phosphorus, - Cipro, tetra: chelation &
- Mg: milk of magnesia stomach in ~30 mins - Short-term sx relief bone marrow reduce dose
- NaHCO3: Alka Seltzer Dose: after meals, HS x 4-6 wks or ONLY – rescue meds suppression, - Warfarin, digoxin,
- Mg2+, Al 3+: Maalox, asxs hypothyroidism quinidine, phenytoin,
Mylanta - Al + Mg = ↓ GI theophylline, isoniazid
Antacids (OTHER) ● Forms highly viscous sol’n that effects - H2 blockers need acid
- Gaviscon: antacid w/ floats on surface of gastric - Alkalosis esp w/ to be absorbed!
alginic acid contents NaHCO3 (worse w/↓ - ↑intragastric pH can ↓
● Protective barrier for esophagus renal fxn) absorption of drugs
against reflux of gastric content - Alkaluria: (azoles), enteric coated
Simethicone: Anti- Alters elasticity of mucus-coated precipitation of may be released
flatulant – commonly bubbles, causing them to break. CaPO4, stones prematurely
added to antiacids - Release of CO2 can - ↑ urinary pH → basic
cause belching, occ urine = ↑ UTI
N, abd distension, - Physical barrier to
flatulence absorption
- Gastric acid secretion
test
Promote mucosal defense for stress related mucosal damage
Risk factors for Prophylaxis: coag (plts <50, INR > 1.5 or Ptt > 2x control), mechanical vent >48 hrs, GI Bleed hx x 1 yr, Brain/spinal trauma, burn pts, 2+ of (sepsis, ICU x 1wk, steroids > 250 mg HCT, GI bleed hx >6d)
Do not prophylax low risk pts and stop prophylaxids once it is not necessary
Misoprostol (Cytotect) Synthetic PGE1 analog - Deesterifcation to free acid; Prevent & tx NSAID GI: N/D, ab pain, Preg cat X Arthrotec: diclofenac +
- Binds to PG receptor on parietal extensively absorbed induced GU dyspepsia, flatulence misoprostol
cell = ↓histamine & acid secretion - Peaks @ 25 mins, T ½:20-40 mins GU: spotting, cramp, DDI: food diminishes
- mucosal protective effects – ↑ - <90% protein bound, 80% recovered hypermenorrhea plasma concentration
mucosal blood flow, ↑ HCO3 & in urine HA Mg containing antacids:
mucous secretions → uterine aggravates diarrhea
contractions
Sucralfate (Carafate) Protects ulcerated tissue from acid, Topical --@ pH 2-2.5 binds to DU, GERD, GI bleed Constipation Preg cat B
inhibits pepsin, absorbs bile salts damaged tissue = barrier → Contra: Dialysis pt
attachment to ulcer x 6hrs Immediate relief w/ ulcers Infreq dry mouth, N, DDI:

2
 DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes
Stimulates endogenous dizzy, rash ↓absorption: TCA, FQ,
prostaglandins, may suppress H. Dose QID azole, PHT, digoxin,
pylori Sz in dialysis pts who warfarin
are receiving Al *Requires acidic pH to be
Contains sucrose moiety – role in containing antacids activated, so shouldn’t
ulcer healing be administered
simultaneously w/
antacids, H2RA or PPI
Bismuth compounds Coats ulcers & erosions Acute D/dyspepsia: 30 ml or 2 tabs - Reduce stool frequency Blackening of stools → Salicylate toxic in renal Good for those who’s
(Pepto-bismol, - Creates protective layer against PO QID & liquidity in infectious educate pts(NOT GI dysfxn – don’t use tried prescription meds
Kaopectate, Helidac) acid & pepsin diarrhea BLEED) and not working
- Stimulates mucous, prostaglandin - Direct antimicrobial - Blacken tongue w/
& HCO3 effects/binds liquid form
entertoxins (traveler’s - Bismuth toxicity →
diarrhea) & HP (trip & encephalopathy
quad dosing) (ataxia, HA,
- Dyspepsia & acute confusion, sz) ➔ in
diarrhea renal dysfxn
More GERD tx – Prokinetic agents → not 1st Line for GERD; pts who fail high dose PPI d/t motility d/o
Metoclopramide - ↑UGI tract motility w/o PO & IV - pts w/ Tachyphylaxis DDI:
(Reglan) secretions GERD: 10-15 mg up to QID known/suspected CNS: extrapyramidal CNS depress: ETOH,
- Sensitizes tissues to Ach motility d/o or inpts effects → irreversible, morphine, diazepam
- Motility effect not dependent on who fail high dose PPI fatigue, drowsiness Reduce absorb: cimet, dig
vagal innervation → stopped w/ - Impaired gastric CV: hypo/HTN ↑absorb: ETOH,
Anti-Ach drugs emptying/DM Endocrine: ↑ prolactin, cyclosporine
- ↑tone and amplitude of gastric gastroparesis amenorrhea, Succinylcholine-
contractions → relaxes pyloric - GERD galactorrhea, ↑neuromuscular blocking
sphincter & ↑peristalsis in - Prevention of post op gynecomastia, d/t inhibition of
duodenum & jejunum; ↑LES tone; N/V impotence cholinesterase
little effect on gall bladder or - Prevention of chemo- GI: N/D, bowel disturb
colon motility. induced emesis
- Antagonizes central & peripheral
DA receptors – antiemetic effect
Cholinomimetic agonists - Stimulate M3 receptor on muscle - Bethanechol – GERD & Neo: salivation, N/V/D, Just know these exist –
Bethanechol cells gastroparesis bradycardia other drugs are better
Neostigmine - Neostigmine – enhance
gastric, SI & colonic
emptying for large
bowel obstruction
Macrolides – - Directly stimulates motilin IV - Gastroparesis
Erythromycin receptors on GI smooth muscle & - UGI hemorrhage to
promotes onset of MMC promote gastric
emptying before
endoscopy

Constipation: > 2 of the following complaints present for at least 12 months when not taking laxatives: straining, incomplete evacuation, <2 BMs in 1 wk
- Tx approach: diet & life-style mod → incr fiber. Correct underlying dz, d/c or lower dose of constipation-causing meds
Drug induced: Analgesic → Opiates (#1), anticholinergics, muscle blocker, antacids, barium, CCB, clonidine, diuretics, Fe supplements
Osmotic Saline – Attract/retain H2O in 0.5-3 hrs onset Cause watery stool (QUICK) Bloating, cramping, gas, incr Intravascular vol depletion,

3
 DRUG
Mg citrate/hydroxide
Mg sulfate
Sodium biphosphate
Stimulant/irritant
Cascara, Senna, Bisacodyl
suppository, Castor oil
Bulk-producing
Methylcellulose,
Polycarbophil, Psyllium
Emollient
Mineral oil
Not recommended – here for
completeness – ie don’t
concentrate too much
Fecal softeners: Docusate
Hyperosmotic:
Lactulose, glycerin suppository
MOA
intestinal lumen increasing
intraluminal pressure; CCK
release
Rapid H20 → distal Small
bowel & colon → high liquid
stool vol. (mg ct/NaP
Direct action on intestinal
mucosa/nerve plexus, alters
water & electrolyte secretion
Holds H2O in stool to ↑ bulk-
stimulating peristalsis, form
emollient gel→distends colon
& promotes peristalsis
In D: absorbs free fecal H2O,
forms gel → stool
Inhibits colonic absorption of
H2O → ↑stool wt & ↓stool
transit time
↓ surface film tension of
interfacing liquid contents of
bowel – permit H2O & lipids
to permeate
Surfactant, stool softeners
PK/DOSE USE ADEs DDI/Contra Notes
Small & large - Acute/chronic constipation thirst electrolyte fluctuations
intestines prevention
- Prompt bowel evacuation: rapid CI: frail, elderly, CHF or renal
Avoid long term H2O movement insuff
use in renal insuff
d/t risk of DDI:
HyperMg Mg-containing: ↓Cipro
- Na polystyrene may bind w/
Mg preventing neutralization
of HCO3→ ALKALOSIS
Colon Semifluid stool/soft stool ▪ Severe abd cramp CI: appendicitis, pregnancy, Except for Senna, can’t
Neurologic impaired, bedbound ▪ Significant fluid & lactation be use long term!
pts electrolyte imbalance
▪ Destruction of myenteric
plexus → colonic dilation
▪ Melanosis coli: darken
colonic mucosa
pigmentation from chronic
use
▪ Senna → Urine
discoloration: discolors
acidic urine yellow-brown &
alkaline urine pink-red, red-
brown
▪ Castor: may induce
premature labor d/t irritant
effect
12-72 hrs onset, *Useful in C&D, IBS, decr Total ↑bloating & flatus Ca polycarbophil w/ tetracycl Safe to use in anti-
works on small & cholesterol & LDL Esophageal, stomach, small diarrheal thus can be
large intestine intestine & colon obstruction helpful for both
Start here and then use other constipation and
meds for constipation tx. diarrhea
- Soften stool
Colon Prevent & tx fecal impaction for - Aspiration: lipid pneumonia Caution w/ pts at risk for Soften stool
relative SHORT period of time - Foreign body rxn in aspiration
lymphoid tissue
- Long term can impair fat
soluble vit absorption
- Leak from anal sphincter
Small & large Prevent dry, hard stools & Allergy – skin rash
intestine straining Stomach/intestinal cramping,
throat irritation
Colon
4
 DRUG
Osmotic balance –
polyethethylene glycol
(Miralax, glycolax)
Chloride channel activator
Lubiprostone
Naloxegol (Movantik)
Methylnaltrexone (Relistor)
MOA PK/DOSE USE ADEs DDI/Contra Notes
Prevent water absorption by Drink 4L over 2-4 Cleansing prior to GI exam, No significant mix w/ H20 or juice daily
intestines hrs tx/prevention of chronic cramps/flatulence
constipation
Stimulates chloride channel - Chronic idiopathic constipation N/D, HA, abd pain & Preg cat C Reserved for failed
opening in intestines – ↑ - IBS w/ constipation: women distension, flatulence therapies, equally as
liquid secretion into >18 yrs, effective as senna!
intestines & shortens transit - Opioid-induced constipation
time (non-cancer)
Peripherally-acting Mu- Many DDIs, - Long term Opioid-induced Abd pain, flatulence, HA, N MANY DRUG Stop all laxative &
antagonists CYP3A4 constipation ONLY INTERACTIONS!!!! CYP3A4 resume after 3 days

Reserved for pts who

failed traditional
therapy

Diarrhea:
Nonpharm: Diet (stop solids x 24hrs, avoid dairy, fasting in osmotic diarrhea, feed children w/ bacterial diarrhea), H20 & electrolytes (vol. depletion → replace, Parenteral & enteral routes if necessary, PO rehydration)
Pharm: anti-diarrheal agents for mild to mod acute diarrhea
- Avoid in bloody diarrhea, high fever or systemic toxicity, IBS, IBD
- Stop if diarrhea worsens
USE: IBS,IBD
Opioid Agonist: Delay intraluminal content Antimotility Difeno&Dipheno w/ atropine: All preg C, except Loperamide = B
❖ Diphenoxylate transit agents - Antichol effect → primarily in children
❖ Difenoxin w/ atropine (discourage -↑gut capacity, prolong - CNS: dizzy, drowsy, HA DDI:
abuse) contact & absorption - GI: N/V, dry mouth CNS depressant
❖ Loperamide: doesn’t cross BBB, -Enkephalins – reg fluid Loperamide: Atropine/antichol, MAOI
no addiction/analgesic effect movement by stimulating - Minor, self limiting ab pain, distention, Cimetidine, ranitidine
❖ Paregoric: tolerance may dev; absorptive process discomfort, N/V, constipation, dry mouth Erythromycin, clarithromycin
agonist activity w/ mu receptor - Fatal arrhythmia tied to misuse/OD/DDI
Bile binding resins Binds bile acid forming 4-5 g TID b4 Bloating, flatulence, constipation, fecal Binds other drugs → preventing
Cholestyramine complexes (fecal excretion) meals impaction, fat malabsorption: ↓bile acid absorption
Colestipol pools Don’t give other drug w/in 2 hrs of
taking bile binding resins
Antisecretory Doesn’t stop diarrhea but has Salicylism effect: tinnitus, N/V DDI: ↓TCN absorption, anticoagulant
Bismuth subsalicylate (Pepto) microbial effects Salicylate induce gout attacks

USE: Prevents travelers’

diarrhea, HP
Octreotide Prolong intestinal transit time; - Injection, SQ CV: sinus brady, arrhythmias, conduction BB, bromocriptine, cyclosporine, This drug works quickly, if it
(Sandostatin) Slows GI motility and reduces (absorbed rapidy abnormalities CYP3A4 didn’t work initially it’s not
intestinal fluid & completely) – CNS: HA, dizziness going to work
duration 12 hrs Inject site pain, flushing, edema, pruritis,
USE: acromeg, carcinoid - peak 0.4 hrs hair loss
tumor, VIPomas, - Somatostatin Endocrine: hyper/hypoglycemia
gastroesophageal varices Short T ½ : 3 min GI: D, loose stools, N, discomfort, stones,
bleeding, GI fistula, diarrheal - Octreotride T ½ steatorrhea, fat-sol vit deficency

5
 DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes
states, dumping syndrome 1.5 hrs
- Adj dose by
response
- Check Renal fxn
MISC PRODUCTS
Lactobacillus → yogurt Lactase enzyme: needed for carb digesting – diary produces lead to osmotic diarrhea
Replaces colonic microflora, restoring intestinal fxn & suppresses pathogenic microorg growth
Dose varies w/ brand → given w/ milk, juice, H20 or cereal
ADE: Intestinal flatus - MC

Irritable bowel syndrome (IBS)

- Idiopathic chronic relapsing d/o; common.
- Noted to also have elevated 5HT3 levels
- Sxs: abd pain & altered bowel habits (diarrhea and/or constipation)
Tx approach:
❖ Diet modifications:
▪ Regular meal patterns, avoid large meals, ↓intake of fat & gas producing foods, caffeine, EtOH, herbals, teas & artificial sweeteners. Avoid lactose/gluten, ↑fiber, eliminate offending itemm
▪ Constipation: ↑fiber➔ dietary fiber 1 tablespoon to TID ➔ use psyllium & try to avoid laxatives!
▪ Pain: use TCA, SSRI, but avoid TCA if pt has constipation
Alosetron (Lotronex) 5HT3 receptor antagonist – CYP450 metabolism Use: Constipation (30%), Prescribing program:
inhibits visceral pain reflex, - Women w/ severe ischemic colitis and severe Lotronex
delays colonic transit, Dose: 0.5 mg BID x 4 wk, ↑ 1 diarrhea predominate IBS constipation →
↑colonic compliance & mg QD if tol. DC after 4 wks - Sx>6 mos hospitalization Not used often
intestinal water/electrolyte if no improvement - Failed conventional tx
absorption
Chloride channel activator: See above in constipation PO BID w/ food - IBS w/ constipation N/D, flatulence, HA Preg cat C Also not very often used
Lubriprostone (Amitiza) IBS: 8mcg - Idiopathic constipation
Idiopathic const: 24 mcg
Anticholinergics Inhibit muscarinic receptor Efficacy for relief of abd sx - Use in pt w/ only diarrhea Antichol effects Can swing a person into
Dicyclomine (Bentyl) in enteric plexus never convincingly IBS no constipation constipation – not great
Hyoscyamine demonstrated choice
Eluxadoline (Viberzi) Mixed mu-opioid receptor ↓dose: hepatic impair or - Fail other therapies ($$$) N, abd pain, constipation, EtOH(>3 drinks/day) d/c if constipation >4 d
agonist (Schedule IV CS) pts w/o gallbladder euphoria, respiratory H/o pancreatitis, sphincter
Intolerance to high dose (asthma, bronchitis, URI) of oddi dysfunction
N/V
Scopolamine Antimotion sickness – ↓ Transdermal patch – apply - Motion sickness Dry mouth, blurred vision,
vestibular input 4-8 hrs prior to embarking, drowsiness, occ confusion &
drug released over 3 days visual hallucinations
(ELDERLY)
Antihistamine & antichol Antimuscarinic, sedative & - Motion sickness Dizziness, sedation Caution: narrow angle
Dimenhydrinate histamine blocking effects - Emesis confusion, possible glaucoma, prostatic
(Dramamine), that lead to antiemetic tachycard, urinary retention, hyperplasia, asthma
diphenhydramine activity, depress conduction visual change
(Benadryl), Meclinzine in inner ear Avoid ETOH → additive
(antivert), Buclinzine effects
(BucladinS), Cyclizine

6
 DRUG
(Marezine)
Phenothiazines
Prochlorperazine,
promethazine
Butyropenones
Substituted benzamides
Trimethobenzamide
Metoclopramide - DOC
Corticosteroids
Dexamethasone,
methylprednisolone
5HT3 antagonists: “-trons”
ondansetron, granisetron,
dolasetron, palonosetron
Neurokinin receptor
antagonist “-pitant”
Aprepitant, fosaprepitant
Cannabinoids
Droabinol (Marinol) Sch III
Nabilone – Sch II
MOA
Block dopamine &
muscarinic receptors in CTZ
Block dopa stimulation
Dopa-receptor blocker
Prostaglandin syn inhibition,
may enhance efficacy of
5HT3 receptor antagonists
Blocks 5HT3 receptor in
vomiting center – blocks
peripheral receptors on
extrinsic intestinal vagal &
spinal afferent nerves
Crosses BBB & occupies NK1
receptors
THC inhibits vomiting
control mechanism
PK/DOSE
PO 300 mg, 200 mg IM TID-
QID
Reduce dose w/ Meto
PO bioavail: 60-75%
CYP3A4 metabolism
Eliminated renal & hep
T ½:
O – 4hrs→ adj. hepatically
G: 5-6 hrs
D: <10 mins → active
(hydrodolasetron) 7 hrs
P: 40 hr
Renal dose unnecessary
1st pass hep metabolism
excreted in feces, urine over
days – wks
USE
- Simple N/V
- Pre/post op
- Mildly emetogenic dose of
chemotherapy
Useful in pts that aren’t on
opiates, allergies & pts that
have failed other tx
- Prevent postop N/V &
emetogenic chem
- Hyperemesis gravidarum
(intractable N/V,
dehydration in pregnancy)
- EPS
- Chemotx induced
- Postop
post-op n/v tx & prevention
Chemotx & radiation-
induced n/v
- Prevent acute & delay N/V
from highly emetogenic
chemo
- Post op
- Appetite stimulant (FDA
Approved)
- Antiemetic in chemo
ADEs
Extrapyramidal rxn (EPS),
HOTN, hypersen rxn w/
possible liver dysfxn,
Lower sz threshold
Rare: blood dyscrasias, QT
prolong
, melanosis, skin necrosis
Extremely sedating, HOTN,
tachy card
EPS: dystonia
EPS: restlessness, dystonias,
Parkinson sx
Mood changes (anxiety to
euphoria), GI irritation,
indigestion, incr appetite,
HA, ab discomfort,
hyperglycemia
Well tol
HA, mild fatigue, HTN,
dizziness, D, constipation, ab
pain
D: QT prolong, incr HR
O & G: ↓HR, QT prolong
Abd pain, fatigue, D,
dizziness, constipation,
dyspepsia, hot flush,
infusion site pain,
induration, HA
MJ type effects: Euphoria,
dizziness, paranoid,
somnolence, drymouth,
tachycard, conjunctival
injection, HOTN
Tolerance developed to
most ADE – not antiemetic
activity
DDI/Contra Notes
DDI: CNS depressant, Not useful bc of
antidepressant sedation & ADEs
Only use in resistant
pts d/t ADE
Just for our information
Metoclopramide readily
available in the US
Other drugs may ↓ hep
clearance.
Atenolol & cimetidine ↑ D
levels
Rifampin ↓D levels.
Avoid QT prolong drugs
Preg cat B
DDI: $$$$
Inhibit metabolism:
docetaxel, imatinhib
↑aprepitant plasma: azole,
FQ, clarithromycin,
verapamil,
↓INR in pts taking warfarin
NO DDI Combo therapy w/
phenothiazine provides
synergistic effects &
reduce ADE
7
 DRUG MOA
Benzodiazepines
Lorazepam, diazepam
Sulfasalazine Metabolized to sulfapyridine
& 5ASA
Anti-inflammatory effects:
Cyclooxygenase or
lipoxygenase inhibition
Inhibit macrophage
production of
cyclooxygenase,
thromboxane synthetasae,
platelet-activating factor
synthetase, and Interleukin-
1 Tablets acts on colon
Superoxide-free radical
scavenger
Anti-inflammatory or
immunomodulatory
properties noted in vitro
(may block cyclooxygenase
and PG production), affinity
for connective tissue, or to
relatively high conc in liver
& intestinal walls
Olsalazine Reduce absorption of parent
drug in SI
Na bioconverted to 5ASA →
COLON
Dimer of 5ASA
Mesalamine 5ASA, absorbed → gut &
Pentasa: stomach, SI, LI liver
timed released
Asacol: SI, LI – pH
dependent
PK/DOSE
Ulcerative Colitis/Crohn’s disease – IBD
Tx depends on clinical severity of IBD
<15% absorbed in intestines
Peak 10 hrs after dose
70% protein bound (SP),
90% (5-ASA)
T ½: fast acetylators 10.4
hrs, slow: 14.8 hrs
- 5-ASA metabolized by
acetylation in liver &
intestine; most 5-ASA
excreted via feces.
Minimally absorbed <10%,
deactivated in colon, liver
99% protein bound
T ½: 7 days
P
20-30% absorbed in UGIT
after PO
PO, enema
USE
- Anticipatory N/V: best
therapeutic alternative
Tx after 1st chemotx,
N/V post= 1st tx
N post 1st tx described as
“moderate, severe or
intolerable”
<50yrs old
Susceptibility to motion
sickness
Feeling warm or hot all over
post-tx
Sweating post- tx
- generalized weakness
- UC
- UC for pts intol of
sulfasalazine
- UC
- Proctitis
- proctosigmoiditis
ADEs DDI/Contra Notes
Treat the following
symptoms:
Dose related: N/V, HA, DDI: cyclosporine digoxin, Rec Folic acid
fever, anorexia, arthralgia folic acid
Hematologic: G^PD  MTX, sulfonylureas,
deficiency hemolytic anemia thiopurines, warfarin
Cyanosis, male infertility,
skin rash, TEN, don’t use in preg!
bronchospasms,
hepatotoxic, lupus like
syndrome, raynaud’s,
nephritic syndrome
D, pain, cramps, N (take w/
food), rash, HA, itching,
arthralgia
Mild & transient
RARE: pericarditis,
pancreatitis, hepatitis
CNS: HA, fever, dizziness,
asthenia
8
 DRUG MOA
Azo compound: LI –
azoreductase in colon by
bacterial
Balsalazide Linked to an inert carrier →
Colazal cleaved in colon &
mesalamine released
Corticosteroid Inhibit inflame cytokine
Prednisone, prednisolone – production, NO synthease,
commonly used PO phospholipase A2, COX2.
Hydrocortisone enemas Reduce expression of
Budesonide - IV inflammatory cell adhesion
molecules
Azathioprine, 6 Immunosuppression &
mercaptopurine (6MP) steroid sparing effect
Methotrexate Inhibit dihydrofolate
PO, SC, IM reductase: Enzyme
important in thymidine &
prurines production
- High doses inhibit cellular
proliferation
- Interfere with IL-1
- Stimulate release of
adenosine, an endogenous
anti-inflammatory
- Stimulates apoptosis &
death of activated T-
lymphocytes
Antimicrobials Interruption of bacterial role
Metronidazole in inflammatory process
TNF inhibitors Decr inflammation & TNF-a
Infliximab (remicade) production
Becomes resistant d/t the
antibodies developed from
this
Adalimumab (humira)
Certolizumab pegol Cimzia
Natalizumab Humanized IgG4
PK/DOSE
750 mg caps, TID x 8 wk
B for crohn’s: PO 9 mg QAM
x 8 wk, repeat for recurring;
UC distal: 2 mg as enema
Dose - uncertain
15-25 mg SC Qwk, response
w/in 8-12 wks, reduce to 15
mg/wk
500 mg PO QID
5 mg/kg @ 0,2,& 6 wks – up
to 10 mg/kg; repeat Q8wks
300 mg q4 wks via IV
USE
- UC
- Mod-severe active IBD
- Not for maintenance of
remission
- Budesonide: Crohn’s &UC
- UC, Crohns – induction
and maintenance
remission → up to 80%
- Induce & maintain
remission in Crohn’s dz
- Crohn’s (induce &
maintenance)
- Reduce # of fistulas
- Mod-severe UC –
eliminate corticosteroid
use
- Induce/maintain remission
of mod-severe Crohn’s
- Maintain response in
mod-severe Crohns
- Crohn’s, who have failed
ADEs
GI: ab pain/cramp,
arthralgia, rhinitis, N/V/D,
dyspepsia
Ab pain, D, anorexia,
flatulence, flu-like d/o
Taper to minimize ADEs
Hyperglycemia, HTN, acne,
osteoporosis, fluid
retention, electrolyte
disturbance, myopathies,
muscle wasting, psychosis
N/V, bone marrow
depressin, hep toxic, severe
leukopenia
Bone marrow depression,
megaloblastic anemia,
alopecia, renal insufficiency
→ leads to hepatic
accumulation & toxicity
Mild, common
Paresthsias, metallic tatse,
glositis, disulfiram-like rxn
Infusion rxn, fever,HA,
dizziness, SOB, chest
discomfort, hep toxic, CNS,
hepatosplenic T-cell
lymphoma, hematologic
events
Infusion rxn, infxn
DDI/Contra Notes
Budesonide: less
effective than
conventional
corticosteroid – less
ADEs
Preg cat D 50-60% achieve
Monitor: CBC, LFTs, reduce remission after 3-6 mos
dose w/ abnormalities tx, remission in up to
DDI: allopurinol (XO) 80%
Genetic: thiopurine
polymorphism: inactivates Allows dose
azathioprine, enzyme reduction/elimination
deficiency at greater risk for of steroids in majority
hep toxic
Preg X Need folate sup
Renal insuff leads to
hep toxic
Preg cat B → can’t breast
feed
DDI w/ warfarin (incr INR)
Need PPD test, typically Clinical response 60-
safe in pregnancy 70%
$$$
50% response
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 DRUG
DRUG
Pancreatic enzyme sup.
Lipase (creon, zenpep,
pancreaze)
Ursodiol (Actigall)
Cirrhosis tx: identify & eliminate cause of cirrhosis
- Assess risk for variceal bleeding & begin pharm prophylaxis
- Portal HTN & variceal bleeding ➔ prevent first bleeding episode, tx acute variceal hemorrhage, prevent rebleeding in pts w/ previous bleed
Non-selective B-blocker (1st
choice)
Propranolol 10 mg TID
Nadolol 20 mg QD
Nitrates (only if they don’t
respond to BB)
Isosorbide-5-mononitrate
10 mg BID and incr 20 mg
TID after 1 wk
Somatostatin & Octreotide
Vasopressin (ADH)
Ascites tx: Paracentesis
MOA PK/DOSE USE ADEs DDI/Contra Notes
monoclonal antibody other tx
Pancreatitis: acute, severe, chronic
MOA PK USE ADE DDI /CONTRA NOTES
140000 IU/h Chronic ab pain, Contain nucleic acids – Fe: enzymes reduce Fe Compliance
delivered post malabsorption/steatorrhea → hyperuricosuria, absorption problems: # of
prandially eliminate abdominal cramping hyperuricemia, kidney caps/dose, freq of
adjust dose for & bloating stone, impair folic dose, cost!
steatorrhea & sx absorption, N, cramp,
colonic strictures &
H2RA/PPI may incr intestinal obstruction (HIGH
bioavail. – helps DOSE)
maintain pH>4 : Hypersen to powder-pork
prevents bile acid protiein
ppt, decr
intragastric vol
Expands total bile salt pool, reduce T ½: ~100 hrs Bile acid therapy for gallstones Diarrhea
hep cholesterol secretion, stabilize – dissolution of small
hepatocyte membrane cholesterol gallstones in
symptomatic gallbladder dz
Early biliary cirrhosis – decr LFT,
improve liver histology
Block adrenergic dilatory tone of Portal HTN & variceal bleeding Reduce by 50% &
mesenteric arterioles= unopposed a- prophylaxis continued lifelong
mediated vasoconstriction & ↓in unless not tol.
portal inflow & pressure
Smooth muscle vasodilation & Nitrats can incr Iso-5-mononitrate:
reduction in portal pressure portal blood flow higher long term
→ incr portal mortality than
pressure by propranolol in >50
enhancing NO yo
mediated
vasodilation of
vasculature
Decr splanchnic blood flow = decr Variceal hemorrhage Hypo/hyperglycemia, Endoscopy (EBL/EIS)
portal blood flow and pressures - if standard therapy fails (2 cardiac conduction primary therapeutic
(portal & variceal) failed endoscopic procedure) ➔ abnormalities tool
balloon, TIPS, surgical shunt
Causes arterial vasoconstriction – IV – continuous Portal HTN, acute GIB HTN, MI, mesenteric Reduce effects of nitro
reduce splanchnic perfusion, lower infusion infarction, N, abd cramps,
portal venous pressure diarrhea, retain free water
(hypoNa, fluid retention, pul
edema, promotes
vasospasm)
10
 DRUG MOA PK/DOSE USE ADEs DDI/Contra Notes
Abstain from ETOH, Na restriction, Spironolactone 100 mg & Furosemide 40 mg QAM
Discontinue: encephalopathy, severe HypoNa, renal insuff (Sc >2 mg/dl)
Spontaneous bacterial peritonitis (SBP)
TX:
- Cefotaxime 2 gm q 8 hrs or 3rd gen cephalosporin.
- All pts who survive an episode of SBP should receive long-term anbx prophylaxis
- Prevention for high risk: Norfloxacin, ofloxacin
- Intermittent prophylactic strategies: cipro, bactrim
Hepatic encephalopathy tx
Nonpharm: limit dietary protein
Drug MOA NOTES
Lactulose - #1 option - Fermented by bacteria in colon, producing organic acids, decr PO, Tube, Enema
colonic pH to ~5
- Acidification of colon inhibits the viability of urease-
Understand mechanism producing bacteria & promote growth of non-urease
bacteria, decr absorption of ammonia
- Acidification also enhances net movement of ammonia from
blood → bowel
- Cathartic effect eliminates ammonia as well as protein
subtrats inhibiting ammonia production
Hyperammonemia:
- Inhibit urease-producing bacteria: Neomycin; Metronidazole
- Others: replace urease-producing bacteria in colon w/ non-urease producing strains (Lactobacillus, Enterococcus faecium, eliminate HP)
- Enhance ammonia removal by stimulating detoxification by supporting alternative metabolic pathways: L-ornithine L-asparatate (OA) → enhances ureagenesis & reduces ammonia concentration. Zn:
cofactor for ammonia metabolism

11