Gastro Pharm 2 Flashcards
Bulk forming laxatives
- hydrophilic muciloid that forms gelatinous mass when mixed with water; allergic rxns, flatulence, borborygmi, intestinal obstruction, may inhibit coumarin absorption
- hydrophilic, digestible, colloid mass w/ water, may bind/ impede Rx absorption
- hydrophilic, polyacrylic resin, absorbs 60-10x their weight in water, Ca+ polycarbophils release calcium that is contra-indicated w/ tetracycline
- Psyllium husk
- methyl cellulose
- polycarbophils
Surfactant laxatives (stool softeners to reduce strain of defecation)
- anionic surfactant, weakly active, stool softener to reduce strain of defecation, no effect on intestinal peristalsis; not for use during abdominal pain, N/V, can irritate the intestinal mucosa, & increase absorption of other Rx, short-term use
- non-ionic surfactant, stool softener, can cause diarrhea, not for use during abdominal pain, N/V
- rapid acting, anionic surfactant that produces catharsis – complete evacuation of the bowels, stimulates intestinal peristalsis; can cause colic, dehydration, electrolyte imbalance, can induce uterine contractions in pregnant women
- Docusates
- Poloxamers
- Caster oil
Stimulant laxatives: act on the large bowel, increase the permeability of intestinal mucosa, increase back diffusion of water & electrolytes, stimulate mucosal mycenteric plexus, stimulate prostaglandin synthesis & increase intestinal secretions, most potent class of laxatives
- prodrug, converted by enteric bacteria to the desacetyl active form; enteric coated; OD can cause excessive fluid loss colonic inflammatory response (synthetic)
- natural derivatives of Lilliaceae plants (senna, cascara)- more gentle than synthetic drugs, work by promoting colonic motility; OD – abdominal pain, nephritis, melanotic pigmentation of colon, abnormal urine color
- Diphenylmethanes - Bisacodyl (swallow hole! would cause cramps in stomach/ SI)
- Anthraquinones - Senokot
Saline/ Osmotic Laxatives – osmotic effect retains water in the lumen of the GI; Mg produce laxation by osmotic effect thru release of CCK, which increases intestinal motility and secretion
- Epson salt
- Milk of magnesia
- Cathartic
Magnesium sulfate
Magnesium hydroxide
Magnesium citrate
Osmotic Laxative given as a fleet enema
Buffered phosphate
now have sodium phosphate tablets
Osmotic Laxative
semisynthetic disaccharide that is not absorbed, produces an osmotic laxative effect; metabolized by enteric bacteria to organic acids such as lactic, formic, acetic acid – fecal acidifier; acidification traps ammonia in the ammonium form which is not toxic
Lactulose
Osmotic laxative
suppository – osmotic/ lubricant effects
Glycerine
Osmotic laxative
dissolved into 4 L and ingested 8 Oz ~ 10 min for colonoscopy where complete evacuation is needed
Polyethylene glycol electrolyte solutuion
Osmotic laxative
mixture of hydrocarbons that penetrates & softens the stool
Mineral Oil
Laxatives for IBS
- activates intestinal chloride channels, in a PKA independent fashion; increases intestinal secretions and motility for chronic idiopathic constipation
- peptide agonist of guanylate cyclase 2C that acts on intestinal cells to indirectly activate the chloride channel
- Lubiprostone
2. Linaclotide
Anti-diarrheal - Absorb etiological factors in the lumen
absorb harmful bacteria, viruses, toxins; tx of traveler’s diarrhea & H pylori
Bismuth sulfate & charcoal
Anti-diarrheal - Absorb water
Cellulose derivatives, semisynthetic polysaccharides: Metamucil
Anti-diarrheal: Opiates & Anti-cholinergics
Opiates
-decrease salivary, gastric, intestinal secretions
-decrease motility of stomach & intestines, -increase muscle tone
-increase tone of sphincters including external anal sphincter – reduces urgency; anti-spasmodics, -decrease cramps
-increases the contact times between the ingested matter & reabsorptive epithelium
- 0.04% morphine in benzoic acid, camphor, anise oil tincture
- merperidine congener that has effect similar to opiates (atropine reduces dose & abuse - anti-cholinergic that crosses BBB)
- (Imodium) – interacts w/ intestinal opiod receptor & inhibits calmodulin
- Paregoric
- Diphenoxylate w/ atropine
- Loperamide
Anticholinergics – reduce vagal stimulation, anti-spasmodic
Quaternary ammonium derivatives of atropine; do not cross BBB, anti-spasmotic & alleviate cramps
- used for urinary frequency – causes retention
- more suited to alleviate cramps
Combined w/ benzodiazapines
- Propantheline
2. Dicyclomine
Motion sickness: Anticholinergics
prophylactic only for motion sickness; cochlear sensation of motion is projected via cholinergic fibers of the auditory nerve to CTZ; blocks M receptor activation by acetyl choline (transderm patch placed behind the ear), sedation, extrapyramidal drowsiness, dry mouth
Scopolamine
H1 antihistamines – older antihistamines exhibit anti-cholinergic effects in addition to anti-histamine H1 effects
Dimenydrinate (Dramamine) – OTC for prophylaxis of MS, 30-60 min prior, will last 4-6 hours
Piperazines - MS
Cyclizines – OTC for MS
Meclizines - depresses hyperstimulation of labyrinthine function; vestibular disturbances
Anti-Dopaminergics/ Anti-emetics – block the dopamine receptors in the chemoreceptor trigger zone (CTZ)
used for management of N/V; Sedation
-Phenothiazine: Promethazine – used for management of N/V; Sedation
Anti-emetic Serotonin Antagonists – Serotonin (5-HT) block 5-HT3 receptors in the stomach & small intestine, these organs transmit stimuli thru vagal and SNS afferents to the CTZ and to the VC thru the solitary tract nucleus; they also block 5HT3 receptors that stimulate the VC to produce emesis; most effective to date; can be used alone or in combination w/ GC & benzodiazapines
1. more potent than odansetron
- longer half-life
- given IV
- Granisetron - more potent
- Dolesetron - longer half-life
- Palonosetron - IV
one of the major substances in marijuana that acts by stimulating the CB-1 subtype of cannabinoid receptors; only in cancer tx when patients have failed to respond to other emetics
Dronabinol
have anti-emetic effects: enhance overall antiemetic effect; MOA is to prevent production of prostaglandins a/w with chemo/radiation
Corticocteroids (Dexamethazone, Methylprednisolone)
P/neurokinin 1 (NK1) receptor antagonist, used as an adjunct to prevent emesis induced by cytotoxic agents; crosses the BBB and inhibits emesis via central actions; oral, CYP3A4 metabolism
Aprepitant
used as an adjuct to other antiemetic regiments; effective in patience w/ anticipatory vomiting because they cause somnolence & amnesia; given prior to chemo;
Benzodiazapine – Lorazepam & Alprazolam
centrally acting anticholinergic/ antidopaminergic, N/V, intractable hiccoughs
Chlorpromazine
poor antipsychotic, but highly useful antiemetic
Prochlorperazine
inhibits CTZ and VC
Thiethylperazine
blocks dopaminergic receptors in the CTZ, post-op for N/V
Butryrophenones: Droperidol
DA receptor antagonist that blocks chemotherapy induced activation of D2 receptors, stimulates gastric emptying; given prophylactically prior to chemo, prevent post-op N/V
Benzamine: metoclopramide
Trimethobenzamide AE
extrapyramidal side effects
Tx carcinoid tumors
interferon alpha
ocreotide
liver cancer 3 drugs
doxorubicin, 5FU, sorafinib
first line for GIST
imatinib
ocreotide
rash is common w/ this mAB to EGFR
Cetuximab
DPD def (familial pyrimidemia) enhances the neurotoxicity of this Rx
5FU
+Leucovorin
gastric acidifier to counterbalance the deficiencies of gastric juice in gastric cancer ; nutritional supplement
Glutamic acid
HER2 mutations in — GI cx?
gastric, trastuzumab
C diff
macrolide; bactericidal – including hypervirulent strains; inhibits bacterial RNA polymerases, no activity against gram-neg, facultative aerobes, enterobacteriaceae, limited effect on normal fecal flora; no cross-resistance w/ other antimicrobials, including rifamycin (different site of action on RNA polymerases), minimal systemization after oral administration (side effect profile comparable to oral vancomycin) – costs more than vancomycin, but may decrease recurrence
Fidaxomicin
C diff
for mild/ moderate, oral; 10% of patients suffer from nausea & metallic taste; readily crosses placenta; long term use is associated w/ peripheral neuropathy of extremities (least expensive)
Metronidazole
Hep B
acyclic phosphonates
nucleotide analog of adenosine-5-monophosphatel; disphosphate that inhibits polymerase and terminates chain; preferred; should be taken w/ a high fat meal to increase bioavailability; could be lipid solubility, stays in the stomach longer; higher incidence of bone turnover & bone fractures; active against HIV and HBV; ARF – monitor Creatinine & BUN
Tenofovir
Hep B
acyclic phosphonates; diphosphate, chain termination
Adefovir
Hep B
Acyclic phosphonates, diphosphonate, chain termination
Tenofovir
Adefovir
Hep B
preferred; d-cyclopentane, guanosine analog; weakly active against HIV; triphosphate inhibits polymerase; food delays absorption
Entecavir
Hep B L nucelosides
Telbivudine
Lamivudine
approved for HIV, good for co-infection w/ HBV; L-isomer of cytosine, triphosphate that inhibits polyermase
Emtricitabine
Hep C
NS3/NS4 serine protease inhibitors; BBW for rash – pruritis – half of patients:
DRESS (Drug Rash w/ Eosinophilia & Systemic Symptoms), SJS, high fat food
Inhibitor for CYP3A4 and P-gp
Telaprevir
Hep C
NS3/NS4 serine protease inhibitors take with food, no rash
Boceprevir
Hep C
high fat meal is beneficial for distribution; enhanced host T cell function, inhibition of host inodine monophosphate dehydrogenase (IMPDH) w/ depletion of guanosine triphosphate, essential for viral RNA synthesis; direct inhibition of RNA-dep RNA polymerase, may only transiently reduce HCV RNA but will normalize ALT; synergistic w/ interferon
Primary toxicity: hemolytic anemia
Ribivirin
