GI Drugs Flashcards
Oral Rehydration Therapy:
Class?
Mech of Action?
Indications (1)?
ADRs?
Interactions?
ORT
Anti-diarrheal
Glucose promotes Na/Cl uptake by enterocytes, water follows in the same direction.
Indication: Significant diarrhea
No ADRs, no interactions
Metamucil:
Class?
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Metamucil
Class: anti-diarrheal
Mech unknown!
Indication - diarrhea
No ADRs
Loperamide (Immodium)
Class?
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Loperamide
Opioid
Mech: 50% more potent than morphine, limited ability to enter CNS
Indication: diarrhea
No ADRs
Laxatives: Luminally active agents
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Laxatives: Luminally active
MoA: Hydrophilic colliods, osmotic agents, stool wetting agents
Indication: constipation
No ADRs
Laxatives: Stimulants or Irritants
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Laxatives: Stimulants/irritants
MoA: Induce a low-grade inflammation in intestines –> promotes accumulation of water in intestines and stimulates intestinal motility
Indication: constipation
No ADRs!
Laxatives: Prokinetics
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Prokinetics
Mech: 5HT4-R agonist, Dopamine-R antagonist, Motilides
Indication: constipation
No ADR!
Antacids
Class?
Mech of Action?
Indications (2)?
ADRs (for MgOH, AlOH, and CaCO3 separately)?
Interactions?
Class: MgOH, AlOH, CaCO3
MoA: neutralized secreted acids (does not change secretion) –> incr pH –> inactivate pepsin
Indication: relief from pyrosis, gastric acid regulation
ADRs: ∆ bowel habits
- MgOH –> laxative properties; bowel purging
- AlOH –> constipation; sequesters drugs and phosphate
- CaCO3 –> incr Ca, –> cholinergic activity to release gastrin
- Overall: systemic absorption of cations
Cimetidine
Class?
Mech of Action?
Indications (3)?
ADRs (3)?
Interactions?
Cimetidine
H2-receptor antagonist
Gastric Acid regulation
MoA: blocks stimulus to parietal cells
Indications: Duodenal ulcers; Uncomplicated GERD; Prevent nocturnal acid release to allow healing.
ADRs: Causes the most side effects via inhibition of CP450 enzymes; gyncomastia; mental confusion
Interaction: CP450 enzymes. Results in reduced clearance, increased concentration of P450 substrates
Cimetidine: when is best time of day to give med?
Effective when given between evening meal and bedtime: can prevent nocturnal acid release to promote healing
Rantidine
Class?
Mech of Action?
Indications (3)?
ADRs?
Interactions?
H2-receptor antagonist
MoA: Blocks stimulus to parietal cells
Indications (same as Cimetidine): Duodenal ulcers, Uncomplicated GERD, Prevent nocturnal acid release to promote healing
ADRs: Does not interefere with P450 activity
Interactions: Less potent androgenic effects compared to Cimetidine
Famotidine
Class?
Mech of Action?
Indications (3)?
ADRs?
Interactions?
H2-receptor antagonist
MoA: Blocks stimulus to parietal cells
Indications (same as Cimetidine): Duodenal ulcers, Uncomplicated GERD, Prevent nocturnal acid release to promote healing
ADRs: Does not interefere with P450 activity;
Interactions: Less potent androgenic effects compared to Cimetidine
Nizafidine
Class?
Mech of Action?
Indications (3)?
ADRs?
Interactions?
H2-receptor antagonist
MoA: Blocks stimulus to parietal cells
Indications (same as Cimetidine): Duodenal ulcers, Uncomplicated GERD, Prevent nocturnal acid release to promote healing
ADRs: Does not interefere with P450 activity;
Interactions: Less potent androgenic effects compared to Cimetidine
Omeprazole
Class?
Mech of Action?
Indications?
ADRs (4)?
Interactions (2)?
Omeprazole
PPI
MoA: PROdrug, metabolite binds irreversibly to H/K ATPase
Indication: GERD
ADRs: Do not give to pts with cirrhosis or hepatic insuff due to decreased elimination; can increase luminal pH and cause decr absorption of other drugs + incr risk of gut infections; Headache; Diarrhea
Interactions: Co-admin with H2 blockers can decr effectiveness of PPI; PPIs inhibit some P450 enzymes resulting in decr clearance.
Sucralfate
Class?
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Gastric Acid Regulation: Sulfated Disaccharides
MoA: binds to damaged mucosal cells, protects them from pepsin and acid (LOCAL effect)
Indication: gastric acid regulation
No ADRs
Misoprostol
Class?
Mech of Action?
Indications (1)?
ADRs?
Interactions?
Gastric Acid Regulation: PGE2 analog
MoA: enhances mucosal protction by decr gastric acid secretion
Indication: prevent NSAID-induced ulcers
No ARDs
Name 5 different prokinetics and what class of Rx they are
Neostigmine - cholinergic
Bethanechol - cholinergic
Domperidone - dopamine antagonist
Metoclopramide - serotonin agonist AND dopamine antagonist
erythromycin - macrolide
How do cholinergics work to modulate GI bowel motility?
What are 2 examples?
How do they work?
What are they largely used for?
What drug has replaced this class of drugs?
prokinetics - increases luminal transport via increasing SM contractions
Examples: Neostigmine and** **Bethanechol
- causes increased ACh availability in the synaptic cleft –> SM contraction
- indications: ileus
note: this has been largely replaced by metoclopramide
What is Domperidone used as?
What is its mechanism of action?
What is it indicate for?
How does this different than Metoclopramide?
Prokinetic
**dopamine antagonist - “it inhibits the inhibition” - **blocks D2 receptors -> decreased inhibition of cholinergic fibers -> increased ACh release -> contractions
Indications: GI dysmotility and anti-emesis
Compared to Metoclopramide: Domperidone does NOT cross the BBB and won’t cause extrapyramidal effects
What is Metoclopramide used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
How does this different than Domperidone?
Prokinetic
serotonin AGONIST & dopamine ANTAGONIST
- activation of serotinin receptors results in increased ACh release -> gastrointestinal contractions
- inhibits D2 receptors “inhibiting the inhibition”: decreased inhibition of cholinergic fibers -> increased ACh release -> gastrointestinal contractions
Indications: Anti-emesis + GI dysmotility (ie post-surgical ileus)
Side effects *IMPT* Extrapyramidal effects (Parkinsonism)
What is erythromycin used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
How does this different than Domperidone?
Prokinetic
motilin analog - activates motilin receptor (MTLR) in the MMC -> enhanced upper GI motility with little or no effect in the colon!
Indications: Gastroparesis
Side effects: tolerance and antibiotic effects (affects GI flora)
What 4 drugs are dopamine antagonists that act to block D2R in the Chemo-Trigger zone?
Which one is the best one to use for chemoRx or irridation-induced nausea? What is the downside of using this particular drug?
- Metoclopramide* (also serotonin agonist) - best to use for ChemoRx/irradiation-induced nausea
- increased extrapyramidal side effects
- Phenthiazine
- Domperidone
What is Ondansetron used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
How does this different than Metoclopramide?
Anti-emetic
Serotonin antagonist - Inhibits 5HT3-R on vagal neurons that innervate the GI -> blocks vagal afferent signal to the vomiting center the in brain -> decrease nausea and vomiting
indications: Chemo- or irradiation-induced nausea, but does NOT cause extrapyramidal symptoms like metoclopramide
ADR: NOT effective for motion sickness (use Diphenhydramine instead)
What is Dronabinol used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
Anti-emetics
- Cannabinoid agonist - Binds cannabinoid receptors in the CNS
- Indications: Prophylaxis for chemotherapy-induced nausea, AIDs anorexia/HIV wasting syndrome
- ADR: High potential for abuse
What is Diphenhydramine used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
Anti-emetic
Histamine antagonist
Indications: Motion sickness (mild, moderate)
ADR: Not useful for treating chemotherapy-related nausea (use metoclopramide or ondasetron instead)
What drugs should you use for motion sickness? (2.5)
Can these be used for chemotherapy-related nausea?
- Diphenhydramine - Histamine antagonist
- Scopolamine - Muscarinic antagonist
- ginger..
CANNOT be used for chemotherapy-related nausea
What is IBS and how is it treated?
What two drugs are given by certified providers that is taken off the market due to life-threatening ADRs?
Chronic or recurrent GI symptoms (lower abdominal pain) not explained by an organic abnormality
- SSRI (Citalopram, Fluoxetine, Parosetine)
- TCA (Amytriptylines)
Drugs taken off the market due to severe ADR:
- Alosteron **-causes ischemic**colitis, constipation, and death
- Tegaserod - causes MI’s, unstable angina, strokes, and ischemic colitis
What is IBD and what are some intestinal symptoms they cause?
extra-intestinal symptoms?
- Chronic inflammatory intestinal conditions of unknown etiology; examples:
- Ulcerative Colitis (Th2-mediated)
- Crohn’s disease (Th1-mediated)
- Sx: diarrhea, abd. pain, bleeding, anemia, wt loss, skin findings
- Extra-intestinal Sx: ARTHRITIS, other d/o’s
There are 5 drugs therapies for IBD.
What are they?
- Sulfasalazine
- Glucocorticoids: Prednisone, Budesonide
- Azathioprine (6-mercaptopurine)
- MTX
- Infliximab (Remicade)
- Adalimumab (Humira)
- Certolizumab (Cimzia)
- Natalizumab
What is Sulfasalazine used for?
What is its mechanism of action?
IBD - Ulcerative colitis
MoA: PRO-drug that is cleaved at the diazo-linkage to mesalamine which acts in the colon (diazo linkage prevents absorption in the stomach or small intestines and allows release of drug in specific areas of the gut!!!)
What are glucocorticoids used for in IBD?
Give an examples…
What some side effects as a result of chronic use?
Acute IBD Flare-ups
ex: Prednisone
Chronic use can result in systemic effects (Cushing, hypokalemia, etc)
Budesonide is also a glucocorticoid indicated for IBD. Which one specifically?
How does it work?
What are the side effects?
Crohns
it is packaged into a capsule that dissolves only when it reaches the ileum, where the pH >5.5
Side effect: High first-pass effect in the liver, causing increased serum levels of with P450/3A4 inhibitors (erythromycin, ketoconazole, grapefruit juice)
Fewer ADRs than corticosteroids, BUT is slightly less effective and is more $$$$
What is Azathioprine (6-mercaptopurine) used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
Immune-modulator for IBD
MoA: PRO-drug + its metabolite mercaptopurine are **biologically active! **
indications: Long-term treatment of moderate-severe IBD (to maintain remission)
ADRs
- Takes several weeks to produce effects, BUT ultimately reduces steroids required to maintain patients in remission
- allergic reactions
- nausea
- hepatitis
- Pancreatitis** (2% risk)
- lymphoma (NHL = 0.04% risk)
- Bone marrow depression (leukopenia)
- Teratogen
What is Methotrexate used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
Immune-modulators for IBD - Crohns
MoA: Inhibit DHFR -> decreased DNA synthesis -> increased cell death, but role in anti-inflammatory mechanism is not well understood!
Indications: Short-term treatment for patients who are steroid-resistant or steroid-dependent
ADR:
- Myelosuppression (reversible with leucovorin (folinic acid) rescue
- nephrotoxicity
- teratogenic
- mucositis
- microvesicular fatty change in liver
What is Infliximab used as?
What is its mechanism of action?
What is it indicate for?
What are the side effects?
Anti-TNFa mAb
MoA: Induces formation of regulatory macrophages that inhibit proliferation of activated T cells and produces anti-inflammatory cytokines
Indications: IBD patients who are refractory to conventional therapies
ADR:
- Potentially dangerous in patients with chronic infections, cancers, or immune deficiencies
- Possible induction of neutralizing antibodies-> drug tolerance
- Serious infections (3% risk)
- Lymphoma (NHL = 0.06% risk)
- Tuberculous
Natalizumab was also an Anti-TNFa mAb. Why was it taken off the market?
not used anymore because it modulates the immune system systemically (receptors are present in the brain -> proliferation of JC virus -> PML)
