lower GI pharm Flashcards
Ondansetron
anti emetic drug Serotonin Receptor (5HT3) Antagonist Side Effects: Very well tolerated, occasionally GI upset (diarrhea, *constipation) and headaches
Metoclopramide
anti emetic
Dopamine Receptor (D2) Antagonists, also some 5HT3 block
used for n/v of chemotherapy
Due to block of D2 receptors at other sites
Side Effects: *Extrapyramidal symptoms (movement disorders)Restlessness, fatigue, drowsiness, diarrhea
Prochlorperazine
anti emetic
Dopamine Receptor (D2) Antagonists
less effective against emetic stimuli in gut (mediated via 5HT3 receptors)
But additional block of M and H1 receptors increases their utility in nausea with motion sickness
Blocking α1 receptors increases potential for hypotension
Side Effects: *Extrapyramidal symptoms (movement disorders)Restlessness, fatigue, drowsiness, diarrhea
Meclizine – Promethazine
Meclizine is an antagonist at H1 receptors. It possesses anticholinergic, cns depressant, and local anesthetic effects. Its antiemetic and antivertigo effects are not fully understood, but its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone.
Diphenhydramine (Dimenhydrinate)
antiemetic OTC agent for motion sickness with antimuscarinic ADRs
Scopolamine
anti emetic Used transdermally for motion sickness
antimuscarinic
Psyllium
used for constipation
Fiber / Bulk-Forming
Usually recommended first
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
Milk of magnesia [Mg(OH2)], magnesium citrate
Most used for mild to moderate constipation
Avoid in renal dysfunction as long term use can lead to electrolyte imbalances
Phosphate enemas
Primarily reserved for fecal impaction
Polyethylene Glycol – Electrolyte Solutions (PEGs)
High volume solutions
Bowel cleansing prior to medical procedures
Contain Na+-K+ salts to prevent net transfer of electrolytes
Smaller volume solutions
For difficult to treat constipation
Daily dose for treatments
Lactulose
Dissacharide metabolized by colonic bacteria to low MW acids osmotic diarrhea increased peristalsis
Alternative for acute constipation - useful in elderly
Bisacodyl, Senna
increase peristaltic activity via local irritation (PG-NO) –> accumulation of water and electrolytes –> increase motility
Usually active within 6-10 hrs po or 15-60 min pr
Effective, potentially dangerous side effects –> electrolyte / fluid deficiencies, severe cramping
Most widely abused class - but safe for chronic use in recommended doses
Wide inter-individual variation in the effective dose
Castor Oil
Contains a triglyceride that is hydrolyzed in the gut to ricinoleic acid
Acts primarily in the small intestine–> stimulate fluid/electrolyte secretion and speed intestinal transit
Castor bean also contains ricin, an extremely toxic glycoprotein
Docusate
dioctyl sodium sulfosuccinate (Colace®)
A surfactant that acts as stool-softener (facilitates admixture of aqueous and fatty substances)
Role is primarily prevention - used in patients with CV disease / hernia / postpartum patients
Often used in combination with stimulant laxative when initiating opioid analgesic therapy
Lubricant (mineral oil, olive oil)
Coats fecal contents preventing colonic absorption of fecal water
Use with caution in very young / elderly due to potential for aspiration into lungs
Methylnaltrexone (Relistor®)
Given SC, doesn’t cross BBB
Expensive ($700 per day)
Constipation: Option for patients taking opioids for non-cancer pain that have failed laxative therapy
Peripherally acting opioid antagonists
Naloxegol (Movantik®)
New pegylated derivative of naloxone given orally
Extensive first-pass metabolism - primarily binds opioid receptors in GI tract only
$10 per day
Activated Charcoal
: efficacy > MgO-tannic acid [Res-Q]
Binds drug in gut to limit absorption (will also bind ipecac)
Effective without prior gastric emptying
Can even reduce elimination half-lives of drugs given IV
Back-diffusion of drug from blood with ion-trapping in stomach
Sorbitol 70%: Recommended, given with charcoal to prevent “briquet” formation
what Drugs Induce Diarrhea
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
how to treat cholera-
glucose + saline rehydration therapy is first line
Doxycycline – tetracycline – macrolide
how to treat giardia
metronidazole
how to treat ETEC
Quinolones - Azithromycin - Rifamaxin
other ID diarrhea info
Shigellosis Ciprofloxacin – Azithromycin
Salmonellosis – Typhoid fever Levofloxacin, Azithromycin
Campylobacter jejuni Azithromycin – Erythromycin
Enterohemorrhagic E. Coli (0157:H7 - EHEC) Antibiotics risk of Hem Urem Syn Antiperistaltics risk of systemic dis
E. Histolytica Metronidazole (systemic)
Paromomycin (lumenal)
How to treat Cdif
Metronidazole* vancomycin – rifaximin
Loperamide
Opioid receptor agonist affecting intestinal motility (), intestinal secretion (), and absorption ( and )
Anti-secretory activity against cholera toxin - WHAT?
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
Polycarbophil
Recognized by FDA as 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]
Rationale to adsorb “toxins” that cause irritation
Taken after each loose bowel movement until controlled
Manages mild to moderate diarrhea
“Formed stools” and perception of decreased fluidity, but small effect on fluid volume excreted
*Avoid use of bismuth subsalicylate in children under 12 y/o (salicylate risk for Reye’s syndrome)
Probiotics
have their place
Select the TRUE statement(s) concerning diarrhea and its management:
Cholera-associated diarrhea is best managed with antibiotics (tetracyclines) plus rehydration therapy
adjunctively prn
Bismuth subsalicylate is preferred in pediatric patients with viral-associated diarrhea
Most cases of EHEC diarrhea can be managed with loperamide and antibiotics
Polycarbophil has utility in both diarrhea and constipation
Giardia is associated with watery diarrhea
Loperamide should be avoided in traveler’s diarrhea (ETEC)
Bismuth subsalicylate is preferred in pediatric patients with viral-associated diarrhea
Most cases of EHEC diarrhea can be managed with loperamide and antibiotics
Polycarbophil has utility in both diarrhea and constipation
Giardia is associated with watery diarrhea
how to treat IBS diarrhea
loperamide
how to treat IBS constipation
tegoserod
