Lower GI Pharm Flashcards
Ondansetron
Granisetron
Serotonin recep (5HT3) antagonists
- good absorption from GI
- hepatic CYP metabolism
SE: well tolerate, occasionally GI upset (diarrhea, constip), headaches
- *greatest efficacy of anti-emetic classes
- prevention/tx of chemo induced n/v
- post op
- n/v assoc w/ post op use of opioid analgesics
Metoclopramide, Prochlorperazine
D2 antagonists
(Metoclopramide also blocks 5HT3)
Droperidol: D2 antag too
- SE: extrapyramidal sx
- restlessness, fatigue, drowsiness, diarrhea
Metoclopramide: for n/v w/ chemo
Prochlorperazine: less effective against emetic stimuli in gut (med by 5HT3 recep); BUT M, H1 block increases utility in nausea w/ motion sickness; blocking alpha1 receptors increases potential for hypotension
Meclizine, Promethazine, diphenhydramine (dimenhydrinate)
Antihistamines
First gen agents:
- good CNS penetration
- additional muscarinic receptor blocking actions
mostly motion sickness and post op emesis
Scopolamine
Anticholinergic agent
mostly: prevent/treat motion sickness
some effect: post op n/v
Transdermal
DOA: 72 h
Dexamethasone
anti-emetic
decreases PG synthesis
PRN anti-emetics
lorazepam
prochlorperazine plus diphenhydramine
metoclopramide plus diphenhydramine
For high level acute vomiting
mod to high: granisetron + dex
mild: ondansetron + dex
Low: dexamethasone
N/v of pregnancy
(not assoc w/ increased fetal risk)
First line:
pyridoxine (B6) + H1 antagonist (doxylamine)
No improvement: D2 antag (prochlorperazine) or metoclopramide (2nd line bc movement disorders)
If dehydrated+ hospitilization: 5HT3 antag (ondansetron) but increases QT!!
Glucocorticoids (methylprednisolone) reserved for refractory n/v (2nd tri)
1st line agent for nausea of morning sickness
Pyridoxine (Vit B6)
used transdermally for motion sickness
scopolamine (muscarinic antag)
OTC agent for motion sickness with antimuscarinic ADRs
dimenhydrinate (1st gen antihistamine)
Used for gastroparesis, risk of EPSE
metoclopramide (D2 antag)
Most efficacious for n/v of chemo & opioids
ondansetron (5HT3 antag)
Drug induced constipation
Antimuscarinic agents:
Antispasmodic agents, overactive bladder agents
Drugs with antimuscarinic side effects:
1st generation antihistamines
Tricyclic antidepressants
Typical antipsychotic agents (esp low potency)
Antacids
Calcium carbonate
Aluminum
Calcium channel blockers (esp. verapamil)
Opioid analgesics
5HT3 antagonists
Meds to treat constipation: first recommendation
Fiber/bulk forming: Psyllium
Fiber/bulk forming agents
psyllium
Approximates physiological mechanism (facilitates passage-stimulates peristalsis via H20 absorption –> bulk expansion)
Effective in 12-24 hrs to 3 days - take with fluids
May combine and interact with other drugs (digoxin / salicylates), so space dosing
Saline (osmotic) cathartics
added to fiber as SECOND step to treat constipation
- non-absorbable ions–> osmotic retention of intestinal water–> increased peristalsis
- also used in purging doses for food/drug poisoning
Milk of magnesia (Mg(OH)2), magnesium citrate:
for mild to moderate constipation; Avoid in renal dysfunction
Phosphate enemas: reserved for fecal impaction
Polyethylene glycol – electrolyte solutions (PEGs)
High vol soln: bowel cleansing bf procedure; has Na/K salts to prevent net transfer of electrolytes
smaller vol soln: hard to treat constip; daily for electrolyte depletion
Lactulose
saline (osmotic) cathartic
dissacharide metab by colonic bacteria to low MW acids–> osmotic diarrhea–> increased peristalsis
alternative for acute constipation– useful in elderly
Stimulant – Irritant Laxatives
**if fiber/saline fail
Bisacodyl
Senna
Castor Oil
Bisacodyl
stimulant/irritant laxative
increases peristaltic activity via local irritation (PG-NO)–> accum water and elec–> increased motility
active in 6-10 h po or 15-60 min pr
effective, could have dangerous SE: electrolyte/fluid deficiencies, severe cramping
Most widely abused class but safe for chronic use in recommended doses
interindividual variation
Castor Oil
Stim/irritant lax
- has triglyceride that is hydrolyzed in the gut to ricinoleic acid
- acts in SI–> stim fluid/elec secretion and speed intestinal transit
-Castor bean has ricin, toxic glycoprotein
Docusate
Stool-Wetting agent and emollient
“Colace”
surfactant that acts as stool-softener (facilitates admixture of aqueous and fatty substances)
Role is prevention - used in patients with CV disease / hernia / postpartum patients
Often in combination with stimulant laxative when initiating opioid analgesic therapy
Lubricant (mineral oil, olive oil)
Stool-Wetting agent and emollient
coats fecal contents
caution in very young/elderly – potential for aspiration into lungs
Peripherally acting opioid antagonists for opioid induced constipation
-failed laxative therapy
Methylnaltrexone:
given SC, doesn’t cross BBB, expensive!!!
Naloxegol
- oral derivative of naloxone
- first pass metab is high
- 10$/d
Drug induced diarrhea (for reference)
Antibiotics (esp. broader spectrum agents): super infection
Colchicine (anti-inflammatory agent for gout)
Digoxin: parasympathomimetic action
Magnesium Antacids: osmotic laxative action
Misoprostol: prostaglandin analog stimulates intestinal musculature
Muscarinic Agonists: increased parasympathetic tone
Reserpine: sympatholytic agent allows parasympathetic dominance in GI tract
SSRIs: elevated synaptic 5HT levels stimulates GI motility
Loperamide
Opioid receptor agonist affecting intestinal motility (mu), intestinal secretion (delta), and absorption (mu and delta)
Anti-secretory activity against cholera toxin
Effective against traveler’s diarrhea, alone or with antibiotics - discontinue if no improvement in 48 hours
Side effects:
Low addiction liability for acute use due to low water solubility (difficult to dissolve and then inject)
Few adverse effects but overdosage can cause CNS depression (esp. in children) and paralytic ileus
Polycarophil
safe and effective (marked capacity to bind free fecal water)
Useful in diarrhea (absorbs 60X weight in H2O) AND constipation (prevents fecal desiccation)
Adsorbents
Kaolin, pectin, attapulgite, charcoal, bismuth subsalicylate
- adsorb “toxins” causing diarrhea
- mild to moderate diarrhea
- only small effect on fluid volume excreted
***Avoid bismuth subslicylate in kids
Probiotics
-commonly Lactobacillus species
Suppress growth of pathogenic organisms restore normal flora possible role in antibiotic-associated, viral, or Traveler’s diarrhea
low dose TCADs and others for IBS
TCADs:relieve abd pain in IBS
diarrhea: loperamide
constipation: osmotic laxatives
Antispasmodics: dicyclomine, hyoscyamine
constipation: Tegaserod (severe)
severe diarrhea: Alosetron
Alosetron
serotonin 5HT3 Antagonist
- reduces pain, inhibits colonic motility
- P450 metab
Use:
severe IBS in women w/ diarrhea (restricted due to risk of ischemic colitis)
Adverse rxn: CONSTIPATION (30%)
Tegaserod
Serotonin 5HT4 AGONIST
–> peristaltic reflex–> gastric emptying and intestinal motility
low oral avail (bf meals)
renal excretion, hepatic metab
Use:
women under 55: IBS pts with constipation
Adverse rxn: diarrhea (early, resolves)
-linked w/ heart attacks, strokes, unstable angina–> restricted use.
