Drugs Week 4 Flashcards
Aprepitant
Chemotherapy antiemetic
Substance P receptor antagonist especially of central “high order center” NK1 centers. Involved in central and peripheral vomiting pathway.
Oral (vs. Fosaprepitant)
Given w/ 5HT3 antagonists and Dexamethasone
A.E. Generally well tolerated; fatigue, dizziness, diarrhea
Metabolized by CYP3A4 –> drug interactions w/ cancer drugs –> worry about bone marrow suppression.
Fosaprepitant
Chemotherapy antiemetic
Substance P receptor antagonist especially of central “high order center” NK1 centers. Involved in central and peripheral vomiting pathway.
IV (vs. Aprepitant)
Given w/ 5HT3 antagonists and Dexamethasone
A.E. Generally well tolerated; fatigue, dizziness, diarrhea
Metabolized by CYP3A4 –> drug interactions w/ cancer drugs –> worry about bone marrow suppression.
Diphydrinate
Antihistamine (anticholinergic)
Antiemetic
A.E. Anitcholinergic (confusion, dry mouth, etc.) ; Drug interactions w/ some abx;
Don’t use w/ morning sickness
Diphenhydramine
Antihistamine (anticholinergic)
Antiemetic
A.E. Anitcholinergic (confusion, dry mouth, etc.) ; Drug interactions w/ some abx;
Don’t use w/ morning sickness
Meclizine
Antihistamine (anticholinergic)
Antiemetic
A.E. Anitcholinergic (confusion, dry mouth, etc.) ; Drug interactions w/ some abx;
Don’t use w/ morning sickness
Dronibinol
Cannabinoid
Act on central cannabinoid receptors. Unknown mechanism, sedation?
Better agents now available, often give w/ phenothiazine –> synergistic
Side effects: sedation, hallucinations, euphoria, dry mouth, and increased appetite (good).
Nabilone
Cannabinoid
Act on central cannabinoid receptors. Unknown mechanism, sedation?
Better agents now available, often give w/ phenothiazine –> synergistic
Side effects: sedation, hallucinations, euphoria, dry mouth, and increased appetite (good).
Dexamethasone/Methylprednisolone
Unkown MOA
Often given w/ 5HT antagonists and NK1 antagonists.
Balsalazide
X-ASA. X group block cox absorbtion in stomach –> bacteria remove X and allow Cox inhibition in colon.
Specific action at colon
First line treatment in mild/moderate UC. Not effective in Crohn’s due to disease severity/inability to get concentrated enough drug.
Minimal A.E.’s.
Mesalamine
X-ASA. X group block cox absorbtion in stomach –> bacteria remove X and allow Cox inhibition in colon.
First drug in class; not specific action at colon. Can be used as suppository (rectum only then).
First line treatment in mild/moderate UC. Not effective in Crohn’s due to disease severity/inability to get concentrated enough drug.
Minimal A.E.’s.
Olsalazine
X-ASA. X group block cox absorbtion in stomach –> bacteria remove X and allow Cox inhibition in colon.
Specific action at colon
First line treatment in mild/moderate UC. Not effective in Crohn’s due to disease severity/inability to get concentrated enough drug.
Minimal A.E.’s.
Sulfasalazine
X-ASA. X group block cox absorbtion in stomach –> bacteria remove X and allow Cox inhibition in colon.
Specific action at colon
First line treatment in mild/moderate UC. Not effective in Crohn’s due to disease severity/inability to get concentrated enough drug.
A.E. Sulfa drug –> hypersensitiivty, decreased folate absorbtion.
40% have severe GI upset, Nausea, headache, arthralgias, and bone marrow suppression.
Budesonide
Specific corticosteoid to think of when treating Crohn’s.
Subject to extensive first pass metabolism –> local rather than systemic effects.
Used in mild to moderate Crohn’s disease involving the ileum and proximal colon.
Infliximab
TNF-a MAB. Activates compliment.
1/3 of patient’s will become refractory –> will develop antibodies vs. antibodies.
Symptomatic improvement in 60% and remission in 30%
A.E. *infections (TB!) , infusion reactions), severe hepatic problems, possibly increased risk of lymphoma (cause vs. exacerbation debate).
Activated Charcoal
Toxin Binding drug used in GI contimination due to its large surface area.
Must be given in at least 10:1 ratio.
Doesn’t bind iron, lithium, or potassium. Binds EtOH and cyanide poorly.
Note useful in cases of poisoning due to corrosive mineral acids or alkalis
Polyethylene Glycol
Hastens removal of toxins and reduce absorbtion
Whole bowel irrigation can enhance decontamination following ingestion of iron tablets, enteric coated medicines, illicit drug filled packets, and foreign bodies.
Used before endoscopic procedures
Also used as an osmotic cathartic.
Ipecac
Use is controversial, especially if treatment is initiated more than 1 hour after ingestion of poison.
Parents should avoid
Local irritant effect as well as acting on CTZ
Emesis may not occur if stomach is empty
Oral dose –> 15-30 minutes
Used to be OTC. Common in medicine cabinets.
Dangerous if corrosive, a petroleum distillate, or a rapidly-acting convulsant is the toxic substance.
-setrons
MOA: Serotonin 5HT3 Antagonists. Blockade of peripheral 5HT3 receptors in GI. Also receptors in CMZ and vomiting centers.
Therapeutic uses: Best for chemo. Prevention (best) and treatment. Useful for ACUTE phase nausea. Also given post op and post radiation. Not good for motion sickness.
Adverse effects: well tolerated; excellent safety profile (esp. compared to alosetron which is used in IBS). MC is constipation, dizziness, mild headach. Small QT elongation (small risk)
Scopolamine
Muscarinic and dopaminergic receptor antagonist in cerebellum. Widely distributed in CNS.
Most effective agent for motion sickness.
Given in transdermal patch to decrease side effects.
Droperidol
Dopamine (D2) Receptor antagonist
MOA: Antagonist at D2 receptors in CTZ. Resetting GI motility and sedation.
Metocloprimide
Dopamine (D2) Receptor antagonist
MOA: Antagonist at D2 receptors in CTZ. Resetting GI motility and sedation. Also decrease DA inhibition of Ach in gut –> increasing motility of entire gut (prokinetic)
Use: Antiemetic, hiccups, and increased gut motility post surgery, vagotomy, gastroparesis, etc.
AE: somnolence, nervousness, agiation, anxiety. Dystonia, parkinsonism, tardive dyskinesia (permanent). Increased prolactin release (impotence, menstral probs, and galactorrhea)
Prochlorperazine
Dopamine (D2) Receptor antagonist
MOA: Antagonist at D2 receptors in CTZ. Resetting GI motility and sedation.
Promethazine
Dopamine (D2) Receptor antagonist
MOA: Antagonist at D2 receptors in CTZ. Resetting GI motility and sedation.
Thiethylperazine
Dopamine (D2) Receptor antagonist
MOA: Antagonist at D2 receptors in CTZ. Resetting GI motility and sedation.
Azathioprine
MOA: Prodrug –> mercaptopurine –> decreased purine synthesis –> decreased DNA synthesis –> decreased B and T cell production.
Given in low doses for the induction and maintenance of remission of UC and Crohn’s. Allow elimination of steroids.
6-mercaptopurine
MOA: Decreased purine synthesis –> decreased DNA synthesis –> decreased B and T cell production.
Given in low doses for the induction and maintenance of remission of UC and Crohn’s. Allow elimination of steroids.
MTX
MOA: DHFR blocker –> decreased DNA synthesis –> decreased B and T cell production.
Given in low doses for the induction and maintenance of remission of UC and Crohn’s. Allow elimination of steroids.
SSRIs
Used in constipation variant IBS.
Increase 5HT in afferent –> increased peristalsis.
Methylecellulose
Bulk laxative
Increase distension –> increase 5HT afferent –> increased peristalsis
Can act as stool stabilizers –> help both diarrhea and constipation.
Use limited by neurons being present and knowing the cause of constipation.
A.E. Allergies, increased flatulence, increase obstruction.
Polycarbophil
Bulk laxative
Increase distension –> increase 5HT afferent –> increased peristalsis
Can act as stool stabilizers –> help both diarrhea and constipation.
Use limited by neurons being present and knowing the cause of constipation.
A.E. Allergies, increased flatulence, increase obstruction.
Psyllium
Bulk laxative
Increase distension –> increase 5HT afferent –> increased peristalsis
Can act as stool stabilizers –> help both diarrhea and constipation.
Use limited by neurons being present and knowing the cause of constipation.
A.E. Allergies, increased flatulence, increase obstruction.
Anthraquinone
Contact Cathartic
Act on large intestine and is less potent.
MOA: Irritation of mucosa? Unknown.
Side effects: Dependency, destroy myenteric plexus w/ long term use. Melanosis coli.
Bisacodyl
Contact Cathartic
Act on large intestine and is less potent.
MOA: Irritation of mucosa? Unknown.
Side effects: Dependency, destroy myenteric plexus w/ long term use. Melanosis coli.
Castor oil
Contact Cathartic (prokinetic)
Act on small and large intestine and is more potent.
MOA: Irritation of mucosa? Unknown.
Side effects: Dependency, destroy myenteric plexus w/ long term use. Melanosis coli.
Castor oil - dehydration, electrolyte imbalance, uterine contraction
Alosetron
MOA: 5HT3 antagonist that causes constipation (doesn’t work as an antiemetic like other -setron’s
Used in dirrhea dominant IBS as last effort. Compassionate use only.
Side effects: 30% have constipation –> 10% must stop due to this –> 0.1% will require hospitalization. 0.3% develop ischemic colitis. Increased side effects w/ inhibitors of CYP1A2 (antidepressants)
Cisapride
MOA: 5HT4 (and some 5HT3) receptor agonist –> increased release of NT from afferent –> increased peristalsis.
Therapeutic use: Use when no other options. Diabetic constipation.
AE - CV toxicity (esp. long QT) –> 85% had preexisting long QT and/or concomitant admin of cyp3A4 inhibitors.
Tegaserod
MOA: 5HT4 receptor agonist –> increased release of NT from afferent –> increased peristalsis.
Therapeutic use: Use when no other options. Constipation dependent IBS.
AE - CV toxicity (esp. long QT) –> 85% had preexisting long QT and/or concomitant admin of cyp3A4 inhibitors.
Loperamide
MOA: Stimulation of enkephalin interneuron (normally inhibited by 5HT) which inhibits peristalsis. Doesn’t cross BBB –> no addictive/euphoric properties (except w/ blockers of p glycoprotein. I.e. Ca blockers or PPIs)
Therapeutic Use: Diarrhea
AE: Abdominal cramps. Toxic megacolon (esp. if pt has UC).
Strongest antidiarrheal and better if diarrhea has started.
Diphenoxylate
MOA: Stimulation of enkephalin interneuron (normally inhibited by 5HT) which inhibits peristalsis. Some can cross BBB –> give w/ atropine for synergy and AEs at euphoric dosese
Therapeutic Use: Diarrhea
AE: Abdominal cramps. Toxic megacolon (esp. if pt has UC). Euphoria and physical dependence.
Strongest antidiarrheal and better if diarrhea has started.
Alvimpopan
MOA: mu receptor antagonists –> block opiate induced constipation.
Use: Short term hosptial patients
AE: MI risk.
Methylnaloxone
MOA: mu receptor antagonists –> block opiate induced constipation
Use: long term use in chronic pain pts/palliative care.
Domperidone
Dopamine (D2) Receptor antagonist
MOA: Decrease DA inhibition of Ach in gut –> increasing motility of entire gut (prokinetic)
Use: Compassionate use only. Esp gastroparesis.
AE: somnolence, nervousness, agiation, anxiety. Dystonia, parkinsonism, tardive dyskinesia (permanent). Increased prolactin release (impotence, menstral probs, and galactorrhea)
TCAs
MOA:
- )Decrease reuptake of NE from postganglionic symp neurons –> increase activation of alpha-2 presynaptic terminals of Ach postganglionic parasympathetic nerves –> decreased Ach release –> decreased motility
- ) Decrease reuptake of DA –> increase actiavtion of D2 –> decrease Ach and motility
Atropine
MOA: Antimuscarinic. Decreased peristalsis (given w/ diphenxolate for synergism and antiabuse)
Macrolides
Stimulate motilin receptors at subclinical doses.
AE: increase resistance to gut flora to macrolides
Goal is to get motilin receptor agonist w/o ABX properties.
Lubriprostone
MOA: CIC-2 stimulant. Increased Cl- secretion.
Use: Chronic constipation; constipation predominant IBS
AE: Very little absorbtion –> minimal. Diarrhea, Nausea, headache; fetal loss in animals
Linaclotide
MOA: Activates guanyl cyclase c –> activates CFTR –> increase Cl- secretion.
Therapeutic uses: Constipation; IBS
AE: Diarrhea; maternal death; increase in juvenile mortality
Crofelemer
MOA: Voltage independent inhibition of CFTR.
Use: HIV diarrhea due to NRTI and proteases.
AE: Little systemic absorbtion
Octreotide
MOA: Somatostatin analog w/ long half life (6-12hrs.). Decreases fluid secretion. Low doses increase motility and high doses inhibit motility.
Use: Off label for severe diarrhea due to dumping syndrome, short bowel syndrome, vagotomoy, AIDS
AE:
- Impaired pancreatic secretion (steatorrhea and poor fat absorbtion)
- Decreased GI motility (Nausea, abd. pain, flatulence)
- Decreased gallbladder activity (stones)
- Poor release of insulin/glucagon
- Hypothyroidism
- Bradycardia
Bismuth Subsalicylate
MOA: Salicylate decreases PG and Cl- secretion in LI. Antimicrobial; binds enterotoxins.
Use: Prevention of traveler’s diarrhea.
Not as effective as loperamide once diarrhea has started.
AE: blackening of stool/tongue. Salicylate tox at high doses.
Lactulose
Osmotic cathartic
MOA: Not absorbed –> osmosis
Use: Constipation esp. when enteric nervous system is disrupted. Decreases plasma ammonia by increasing growth of bacteria that make NH4+ –> hepatic encephalopathy.
AE: Bacterial overgrowth –> flatulence/abdominal discomfort
If systemically absorbed –> intravascular volume depletion and electrolyte imbalances. Safe in most patients, but dangerous in frail, elderly, renal insuf, cardiac disease.
Magnesium hydroxide
Osmotic cathartic
MOA: Not absorbed –> osmosis
Use: Constipation esp. when enteric nervous system is disrupted.
AE: High magnesium in renal failure pts.
If systemically absorbed –> intravascular volume depletion and electrolyte imbalances. Safe in most patients, but dangerous in frail, elderly, renal insuf, cardiac disease.
Sodium phosphate
Osmotic cathartic
MOA: Not absorbed –> osmosis
Use: Constipation esp. when enteric nervous system is disrupted. Decreases plasma ammonia by increasing growth of bacteria that make NH4+ –> hepatic encephalopathy.
AE: If systemically absorbed –> intravascular volume depletion and electrolyte imbalances. Safe in most patients, but dangerous in frail, elderly, renal insuf, cardiac disease.
Cholestyramine
MOA: Decrease reabsorbtion of bile salts. In secretory diarrhea (crohn’s or ileal resection) they bind unabsorbed bile salts to decrease H20 secretion
AE: GI bloating, flatulence, constipation, fecal impact ion. Impaired absorbtion of other drugs and ADEK
Colestipol
MOA: Decrease reabsorbtion of bile salts. In secretory diarrhea (crohn’s or ileal resection) they bind unabsorbed bile salts to decrease H20 secretion
AE: GI bloating, flatulence, constipation, fecal impact ion. Impaired absorbtion of other drugs and ADEK
Docusate
MOA: Surfactant that lubricates stool
Use: widespread; ? effectiveness
Few AEs
Mineral Oil
MOA: Lubricates stool
Use: widespread; ? effectiveness
AE: Severe lipid pneumonitis if aspirated. Decreased absorbtion of ADEK
