Drugs are bad, m'kay.... Flashcards
proton pump inhibitors (PPI)
oral once a day
IV: GI ulcer bleeding (not FDA approved)
SUPERIOR to H2 blockers
-prazole
irreversible inhibition of H/K ATPase
acid labile: ENTERIC COATING: erratic absorption
taken up by parietal cells and protonated to trap there: short T1/2 but effect lasts longer
metabolized by CYP2C19, 3A4
most effective for basal and food stimulated acid
take BEFORE FOOD
NO tolerance develops
Tx: hyperacidity: GERD, PUD, ulcer bleeding (not approved)
AE: slight increase in enteric infections, possible rebound acid secretion on withdrawal, possible increase risk of fractures
may be CI in Vit. B def. due to reduced absorption
H2 blocker
-tidine
competitive antagonists
take before bed: most effective for basal/overnight acid (doesn’t help for mealtime acid)
MODEST inhibition of gastric secretion from parietal cells
TOLERANCE within days
Tx: hyperacidity: GERD (only in mild cases), PUD (no longer recommended since PPI is superior and H. pylori assoc.); basically just for mild intermittent heartburn
ranitidine
H2 antagonist
cimetidine
H2 blocker
CYP inhibitor
drug interactions: phenytoin, warfarin, theophylline
nizatidine
H2 blocker
famotidine
H2 blocker
esomeprazole
PPI
drug interaction: possibly clopidogrel
lansoprazole
PPI
omeprazole
PPI
nasogastric or orogastric tube: in formulation with NaHCO3 for accelerated absorption rather than enteric coating: only PPI approved for upper GI bleed
also oral enteric coat form
CYP inhibitor
drug interactions: phenytoin, warfarin, diazepam, possibly clopidogrel
rabeprazole
PPI
mesalamine
5-aminosalicylic acid
Tx: ulcerative colitis (orally and rectally)
continue rectal until bleeding stops
stay on oral
bulk-forming laxatives
hydrophilic: form mass when mixed with water
in lumen: absorb and retain water and increase bulk in GI: stimulate stretch receptors to peristalsis
Tx: constipation
carboxymethylcellulose (Citrucel)
bulk-forming laxative: colloid mass
digestible
AE: impedes concurrent drug absorption
OFF LABEL: IBS-C
metamucil (Psyllium)
bulk-forming laxative: gelatinous mass absorb water Tx: constipation, diarrhea AE: flatulence, esophageal obstruction, choking, allergic rxn may inhibit warfarin absorption OFF LABEL: IBS-C
polycarbophils (Mitrolan)
bulk-forming laxative: polyacrylic resins
absorb 60-100x their weight in water
Tx: IBS-C
CI: Ca2+ release may chelate tetracyclines
osmotic (saline) laxative
Mg cations or other non absorbable molecules (Phosphate)
osmotic: retain water in lumen of GI tract: stimulate stretch receptors in increase cholinergic activity in ENS
Ex: Mg sulfate, hydroxide, citrate (citrate is cathartic); Pi containing given as enema or tablet
CKK release: increase intestinal motility and secretion
Tx: constipation
lactulose
osmotic laxative
non-absrobable disaccharide
fecal acidifier: metabolized to organic acids: lactic, acetic, formic: traps ammonia in ammonium form (slows diffusion into blood)
decreases glutamine and NH3 absorption
Tx: constipation; portal-systemic encephalopathy (adjunct to protein restriction and supportive Tx)
polyethylene glycol (PEG; Golytely)
osmotic laxative
dissolve in 4 L water
Use: bowel prep for colonoscopy, constipation, IBS-C
CI: bowel obstruction (nausea, vomiting, abdominal pain or distention) or perforation
docusate sodium (Colace)
anionic surfactant laxative
stool softener: reduce strain of defecation
NO direct stimulatory effect on peristalsis
Tx: constipation
CI: abdominal pain, vomiting
AE: irritate intestinal mucosa, increase absorption of other drugs
SHORT TERM use
chloride channel activators
laxative
increase volume and hydration of stool: stretch recpetors cause peristalsis
Tx: constipation, IBS-C
AE: abdominal distention and pain, diarrhea, flatulence
linaclotide
chloride channel activator: increase intestinal secretion and motility
CFTR
agonist of GC (guanylate cyclase) C2; cGMP; PKG: INDIRECT activation of chloride channel
Tx: constipation (idiopathic and IBS-C)
CI: in children less than 6 yrs
lubiprostone
PGE1: chloride channel activator: increase intestinal secretion and motility DIRECT: CLC channel PKA INDEPENDENT Tx: constipation (IBS-C) AE: nausea
loperamide
opiate agonist
binds calmodulin
chloride secretion blocker and enteric neural blocker: direct action on sm. muscle to slow motility
Tx: diarrhea
AE: hyperglycemia, GI pain (N/V); somnolence
OFF LABEL: IBS-D
opiate antagonist
Tx: opiate induced constipation
methylnaltrexone
opiate antagonist
AE: abdominal pain, flatulence, nausea, GI perforation (increased risk with compromised structural integrity)
naltrexone
opiate antagonist
AE: reverses analgesia (cautious in pain patients)
opiate agonist
What do you add and why?
- decrease secretions and motility
- increase muscle tone of sphincters
- anti-spasmodics: decrease cramps
Tx: diarrhea
add ATROPINE: prevent opioid abuse
paregoric
opiate agonist
add atropine
Tx: diarrhea
diphenoxylate
opiate agonist
add atropine
Tx: diarrhea
stimulant laxatives
most potent laxatives
act on large bowel
1. increase permeability of intestinal mucosa: increase back diffusion of water and electrolytes into lumen
2. increase contractility by stimulating myenteric plexus
3. stimulate PGs: increase secretions
Tx: constipation
senna (anthraquinone)
stimulant laxative
natural derivative: more gentle
Use: bowel prep for colonoscopy
AE: finger clubbing (with abuse), electrolyte imbalance and nephritis (excessive use); dark pigmentation of colonic mucosa, pink urine
bisacodyl (diphenylmethane; dulcolax)
stimulant (ENS) laxative
prodrug: converted to desacetyl by bacteria
enteric coat
local axon and segmental reflexes stimulated: produces widespread peristalsis
effective in SPINAL CORD INJURY
AE: excessive fluid and electrolyte loss leading to colonic inflammatory response
castor oil
surfactant laxative
rapid
irritates mucosa: cathartic effect
AE: colic, dehydration, electrolyte imbalance, uterine contraction
mineral oil
stool softener
mixture of hydrocarbons
Tx: constipation
AE: anal irritation, fecal incontinence
poloxamer 188
non-ionic surfactant stool softener Tx: constipation AE: diarrhea CI: GI pain or N/V (promotes diarrhea)
anticholinergics
regular vs. quaternary
reduce vagal stimulation; anti-spasmodic
Tx: diarrhea
often combined with: benzodiazepine sedative
REGULAR
use: IBS diarrhea
AE: indiscriminate anti-muscarinc activity
QUATERNARY
do NOT cross BBB: no CNS activity
use: antispasmodic (alleviate cramps), antidiarrheal
AE: xerostomia, vision change, bradycardia followed by tachycardia, impotence, bladder, flushing, annhidrosis
atropine
anticholinergic
Tx: IBS
use: combine with opioids to prevent abuse
dicyclomine
anticholinergic
quaternary amine
Tx: diarrhea, IBS
more suited to alleviate cramps
glycopyrrolate
anticholinergic
OFF LABEL: IBS
propantheline
anticholinergic
quaternary amine
Tx: diarrhea
more suited for urinary retention
bismuth subsalicylate
antidiarrheal, antiinflammatory
- stimulates fluid/electrolyte absorption across the intestinal wall (antisecretory action)
- inhibits PG synthesis (reduces intestinal inflammation and hyper motility)
- binds toxins produced by E. coli
use: H. pylori quadruple therapy, prevent traveler’s diarrhea
methysergide
serotonin inhibitor
Tx: carcinoid tumor
inhibits serotonin induced diarrhea
serotonin antagonist
-setron: 5HT3 blockers
Tx: diarrhea or emesis
alosetron
serotonin (5HT3) antagonist
little affinity for dompaminergic or other serotonin receptors
Tx: IBS-diarrhea
AE: COLITIS and SEVERE CONSTIPATION (BBW), arrhythmia, obstruction, perforation, toxic megacolon
physician must enroll in PRESCRIBING PROGRAM
use in combo with corticosteroids with/out benzodiazepines
amoxicillin
penicillin: binds PBP
use: H. pylori triple therapy
resistance does not develop
AE: diarrhea
clarithromycin
macrolide use: H. pylori triple therapy low order of toxicity RESISTANCE: do NOT use more than once in H. pylori AE: taste disturbance, diarrhea
metronidazole
oral
IV: complicated C. diff disease
use: C. difficile (mild-mod), H. pylori triple therapy if allergic to penicillin
RESISTANCE can develop: change dose if use again in H. pylori
CI: PREGNANCY, BREAST FEEDING
AE: peripheral neuropathy, disulfarim effects, diarrhea
tetracycline
Tx: H. pylori quadruple therapy
resistance does not develop
AE: diarrhea, teratogen
fidaxomicin
macrolide: inhibits bacterial RNA polymerases
remains in GI: little systemization
Tx: C. difficile (not recommended yet)
SUPERIOR response (and less recurrence) in high risk C. diff to vanc
AE: GI (N/V; abdominal pain, bleed)
EXPENSIVE
stool transplant
colonoscopy (seems to be best way): blended with saline and filtered through gauze
gastroscopy
NG tube
microbiome replacement
recipient: STOP antibiotics 203 days before; colonoscopy prep to reduce stool; loperamide after transplant
donor: no recent antibiotics; screen for pathogens; test for Hep. A/B/C, syphilis, HIV; milk of magnesia as softener
Tx: C. difficile
vacomycin
oral
IV: complicated C. diff disease
rectal: ileus, distention, anatomic/surgical abnormalities pts (when oral can’t reach colon)
extended Tx with oral: 2nd recurrence
cell wall synthesis inhibitor: binds D-ala, D-ala
Tx: C. diff (severe, pregnant/lactating women)
AE: hypokalemia, abdominal pain, diarrhea, N/V
aluminum hydroxide
antacids
AE: constipation
magnesium carbonate
antacids
AE: diarrhea
antacids
weak bases: neutralize acid most non-absorbable: Mg, Al, Ca avoid: absorbable/systemic agents (NaHCO3) rapid onset, short duration Tx: heartburn AE: Al or Ca based: constipation, Mg based: diarrhea; hypophosphatemia absorbable: alkalosis, Na overload Combo balances AE?
methylprednisolone
corticosterone
use: adjunctive antiemetic for chemo
used in combination with serotonin (5HT3) antagonist +/- benzodiazepine
misoprostol
PGE1 analogue
use: protection against NSAID ulcers
not used much: multiple doses and AE
AE: abortifacient, diarrhea
octreotide
inhibits: serotonin, gastrin, VIP, secretin, motilin, pancreatic polypeptide
use: GI carcinoid tumor
AE: bradycardia, arrhythmia, gallstones
monitor: blood glucose, thyroid function
aprepitant
antiemetic NK-1 antagonist
use: adjunctive antiemetic for chemo
metabolized by: CYP3A4
droperidol
post-synaptic GABA binder
use: antiemetic: PONV
selectively blocked postsynaptic alpha adrenergic receptors
AE: vasodilation, hypotension
metoclopramide
antiemetic, gastric motility potentiator
Tx: paralytic ileus
AE: tardive dyskinesia (often irreversible movement disorder)
sucralfate
oral
adherent proteinaceous exudate: coat over ulcer (about as useful as H2 blocker)
can bind bile salts and other drugs (delay drug absorption)
Tx: peptic ulcer (not really anymore); bile reflux into stomach (lacks evidence)
AE: hyperglycemia in diabetics, use caution in impaired swallowing, constipation (has Al)
CI: PPI, H2 blockers (sucralfate needs acidic pH to work)
sulfasalazine
anti-inflammatory immunomodulator
Tx: ulcerative colitis
AE: dizziness, male impotence, blood dyscrasia
protease inhibitors
-previr
PO: possible interactions
Tx: hepatitis C
simeprevir
2nd gen: protease inhibitor: NS3/4A
Tx: chronic hepatitis C
resistance develops
more genotypes, once daily dose, fewer AE
sofosbuvir
CATALYTIC inhibitor: NS5B nucleotide/nucleoside inhibitor Tx: chronic hepatitis C AE: exacerbates IFN induced anemia PANGENOTYPIC ACTIVATION req: phosphorylation: delay in onset resistance uncommon P-gp
telaprevir
oral (multiple dose) 1st gen: protease inhibitor: NS3/4A resistance develops AE: RASH CI: teratogen (male/female)
boceprevir
oral
1st gen: protease inhibitor: NS3/4A
resistance develops
CI: teratogen (male/female)
ribavirin
inhibition of RNA dependent RNA polymerase
enhance: T cell immune clearance
inhibition of IMPDH (inosine monophosphate dehydrogenase)
increase bioavailability: high fat meal
Tx: chronic Hep. C
AE: HEMOLYTIC ANEMIA, TERATOGEN (male and female), embryocidal
CYP
monitor: hematocrit
synergism with IFN
NO CYP
interferon- pegylated
IM or SC
upregulates immune system: binds receptor: activate TK
endoribonuclease: cleave ss RNA
inhibitory effect on darn
inhibition of viral penetration and uncoating and/or assembly and release
enhanced lytic effects of cytotoxic T lymphocytes
Tx: Hep. B and C
AE: neuropsychiatric BBW (depression, seizure, confusion), thyrotoxicosis (in susceptible pts), flu like; BLOOD DYSCRASIA, LIVER
can develop neutralizing Ab: lose responsiveness
monitor: LFTs, TGs
adefovir
reverse transcriptase inhibitor 2P form produces chain termination prodrug: adefovir dipivoxil Tx: chronic Hep. B resistance develops cross-resistance: tenofovir monitor: LFT
reverse transcriptase inhibitors
oral false building blocks: nucleoside analogs inhibit DNA pol req. 3P for activity Tx: chronic Hep. B monitor: Cr/BUN, phosphate resistance develops NO CYP activity reduce dose in renal dysfunction AE: LIVER (lactic acidosis, steatosis)
emtricitabine
reverse transcriptase inhibitor
if HIV: give with tenofovir
entecavir
PREFERRED reverse transcriptase inhibitor food delays absorption long half life monitor: LFT
lamivudine
reverse transcriptase inhibitor
cross-resistance: telbivudine
short half life
telbivudine
reverse transcriptase inhibitor
cross-resistance: lamivudine
monitor: LFT
tenofovir
PREFERRED reverse transcriptase inhibitor: chain termination prodrug form: tenofovir disoproxil high fat meal: increase bioavailability AE: acute RENAL failure, BONE pain and fractures CI: NSAIDs, other nephrotoxic drugs give CALCIUM and VIT. D cross-resistance: adefovir if HIV: give with emtricitabine
infliximab
TNF-alpha antibody
Tx: inflammatory bowel disease
AE: immunosuppression (reactivation of latent TB, increased susceptibility to infection)
etanercept
soluble TNF receptor antagonist
Tx: pancreatic CA
AE: GI, prolonged bleeding, elevated LFTs, ocular
amifostine
IV
cytoprotective agent: free radical scavenger
use: radiation induced salivary gland damage
AE: hypotension, diarrhea, N/V
ORPHAN DRUG
TNF antagonists
?
cevimeline
parasympathomimetic: M3 (lacrimal and salivary) greater than M1 (CNS)
CYP
Tx: xerostomia
pilocarpine
parasympathomimetic: all M receptors (greater CNS activity)
Tx: Sjogren’s syndrome, xerostomia
caution: psychosis
parasympathomimetics
oral
Tx: xerostomia
CI: asthma, closed angle glaucoma
caution: angina, breastfeeding, arrhythmia, cardiac disease, kids, cholelithiasis, COPD, bronchitis, operating machinery, geriatric, MI, nephrolithiasis, pregnancy
rifaximin
oral
rifampin analog: inhibits bacterial DNA dependent RNA pol
GI confined
Tx: portal systemic encephalopathy
AE: peripheral edema, ascites, dizziness, nausea; fecal urgency and constipation; GI
OFF LABEL: IBS-D
bevacizumab
anti-VEGF mAB
Tx: colorectal CA
AE: GI perforation, dehiscence, bleeding
EGFR inhibitors
AE: rash
cetuximab
anti-EGFR mAB
Tx: colorectal CA
erlotinib
EGFR TKI
Tx: pancreatic CA
AE: edema, increased LFTs
glutamic acid
counterbalances HCl deficiency in stomach
Tx: gastric CA
imatinib, STI-571
bcr-abl TKI
Tx: GIST (gastrointestinal stromal tumor)
AE: GI dysfunction, fluid retention, edema
sorafenib
multi-kinase inhibitor
Tx: liver CA
AE: hand-foot syndrome
sunitinib
multi targeting TKI
Tx: GIST
AE: thrombocytopenia, QT prolongation, GI perforation
trastuzumab
HER2 monoclonal Ab
Tx: gastric CA
AE: LVEF dysfunction, cardiomyopathy
tricyclic antidepressants
Tx IBS pain
hyoscyamine
Tx IBS pain
H. pylori triple therapy
complex: poor patient adherence
1. PPI
2. clarithromycin and amoxicillin (metronidazole if allergic)
H. pylori quadruple therapy
complex: poor patient adherence
1. PPI or H2 blocker
2. bismuth
3. metronidazole and tetracycline
wheat dextrin (Benefiber)
isolated, non-digestible carbs
MoA: increase delivery of water to colon, increase bulk, reduce pressure in sigmoid colon
results in more formed stools
Tx: constipation
glycerin
osmotic and lubricant laxative
suppository
Tx: constipation
General AE of laxatives
overuse leads to constipation that takes days to accumulate bulk
lag in defection interpreted as continued constipation
take more laxatives
can make BOWEL UNRESPONSIVE
octreotide (somatostatin)
decreases vasodilators (like Glucagon) Tx: varices due to portal HTN, hepatorenal syndrome
vasopressin
Tx: varices due to portal HTN
diuretics
Tx: ascites due to portal HTN
pentoxifylline
TNFa inhibitor
Tx: ALD
desferoxamine
IV
Fe chelator
Tx: hemochromatosis
deferasirox
oral
Fe chelator
Tx: hemochromatosis
use when patient has low hemoglobin (thalassemia, sickle cell)
penicillamine
Cu chelator
Tx: Wilson’s
AE: lupus, hepatotoxicity, neuropathy, GI
trientene
Cu chelator
Tx: Wilson’s
AE: sideroblastic anemia
tetrathiomolybdate
Cu chelator
Tx: Wilson’s
zinc
Cu chelator, cofactor in NH3 metabolism
Tx: Wilson’s, hepatic encephalopathy
AE: GI
N-acetylcysteine
give no matter how late they present and even in low acetaminophen levels
Tx: acetaminophen overdose, or regular dose in alcoholic
What is the goal for making drugs to Tx Hep C?
increase compliance
once daily dosing: combination pills and take fewer times a day
also to Tx DIFFERENT GENOTYPES
downside: expensive
dasabuvir
inhibitor: NS5B ALLOSTERIC: non-nucleotide/side Tx: chronic hepatitis C CYP2C8, P-gp AE: well tolerated, dermal, GI
paritaprevir
2nd gen: protease inhibitor: NS3/4A
Tx: chronic hepatitis C
resistance develops
more genotypes, once daily dose, fewer AE
ledipasavir
inhibitor: NS5A
Tx: chronic hepatitis C
ombitasvir
inhibitor: NS5A
Tx: chronic hepatitis C
daclatasvir
inhibitor: NS5A
Tx: chronic hepatitis C
-previr
NS3/4A inhibitor
protease inhibitor
Tx: Hep C
-asvir
NS5A inhibitor: prevents replication unknown function PANGENOTYPIC action: highly conserved site Tx: Hep C CYP interactions
-buvir
NS5B inhibitor polymerase inhibitor Tx: Hep C CYP interactions req. ACTIVATION: phosphorylation
Why would you give combination drugs for chronic HBV?
diminish resistance
Hep C drugs in general interaction
CYP
Initial approach to IBS Tx
lifestyle and dietary modification
reserve drugs for mod. to severe
TCA
CNS
reduce repute of NE and serotonin
some have anticholinergic activity
Tx: IBS-D
SSRI
CNS
selective serotonin reuptake inhibitor
Tx: IBS-D
probiotics
Tx: IBS
small benefit; not routinely recommended
Drugs that cause xerostomia
- antihistamines
- decongestants
- antidepressants
- antipsychotics
- antihypertensives
- anticholinergics
saliva substitutes
Tx: xerostomia
no strong evidence but might as well
Drugs to Tx Sialorrhea
- label
- off label
- glycopyrrolate
2. botulinum toxin, scopolamine
For some drugs like Fosamax/alendronate why are there such specific instructions for taking the pill?
can get irritation and bleeding ulcers if it gets stuck
pop-bottle method
tablet: sinks
fill bottle, put tablet on tongue and close lips around bottle, take drink and purse lips (sucking), swallow
bottle will squeeze (don’t get air in)
lean-forward technique
capsule: floats
put capsule on tongue, take sip of water, bend head forward then swallow
