GI Drugs Flashcards by Jennifer Cromwell

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

How well did you know this?

Not at all

Perfectly

Metamucil:

Class?

Mech of Action?

Indications (1)?

ADRs?

Interactions?

Metamucil

Class: anti-diarrheal

Mech unknown!

Indication - diarrhea

No ADRs

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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!

How well did you know this?

Not at all

Perfectly

Laxatives: Prokinetics

Mech of Action?

Indications (1)?

ADRs?

Interactions?

Prokinetics

Mech: 5HT4-R agonist, Dopamine-R antagonist, Motilides

Indication: constipation

No ADR!

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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 ## Footnote 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)