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GI Drugs Flashcards

0
Q

Pharmacologic of Acid Control

Where does H2 blockers, PPIs and Antacid work?

A

H2 blockers work on Parietal cells in the fundus by blocking histamine from binding to histamine receptors on parietal cells.

PPIs work IN the parietal by inhibiting the H/K ATPase

Antacids neutralize acid in the lumen of the antrum of stomach

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1
Q

What are the 5 classes of drugs for acid peptic disease?

A
  1. Motility Promoters
  2. Drugs for IBS
  3. Anti-Emetics
  4. Drugs for IBD
  5. Other Agents
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2
Q

How do you treat Peptic Ulcer Disease?

A

Heal ulcers by suppressing acid secretion (antacids, H2 antagonists, PPIs)

Enhance mucosal defense (Sucralfate, Bismuth, Misoprostol (only for NSAID ulcers))

Treat H. Pylori (triple therapy with PPI, clarithromycin and ammox)

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3
Q

What are the 4 antacids (weak bases) that neutralize acid?

A
  1. Mg(OH2) Milk of Mg…Laxative and could cause hyperMgemia in kidney failure
  2. Al(OH3)xMg Maalox…Constipation (Al) and diarrhea (Mg) but mostly diarrhea. Al can cause PO4 depletion
  3. NaHCO3 Alka Seltzer…Transient metabolic alkalosis, high Na. NOT FOR PEPTIC ULCER DISEASE
  4. CaCO3 Tums…Causes rebound acid secretion. Also MILK ALKALI SYNDROME (high Ca, PO4, and HCO3 levels)
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4
Q

How do H2 Receptor Antagonists work? When is the best time to give them?

A

These drugs are used in peptic ulcer disease by blocking HCl secretion elicited by Histamine, Gastrin, and ACh. This causes:

Lower Gastric Acid and Pepsin secretion
Higher pH

Also suppresses nocturnal acid secretion so these ARE BEST GIVEN AT NIGHT

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5
Q

What are the 4 H2R blockers?

A
  1. Cimetidine (Tagamet)…potency=1
  2. Ranitidine (Zantac)…4-10
  3. Nazitidine (Tazac, Axid)…4-10
  4. Famotidine (Pepcid)…20-50

Cimetidine has most SEs…may interfere with Warfarin and phenytoin via P450. Also cause HA, N/V, dizziness, myalgia

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6
Q

What is the MOA of PPIs?

A

These are pro-drugs that are not functional at a neutral pH. Need an acidic pH of at least 5. In an acidic environment, they change into SULPHENAMIDE/SULPHENIC ACID which interacts with the sulfhydryl groups on the H/K ATPase, and thereby IRREVERSIBLY INHIBITING IT.

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7
Q

What are the 4 PPIs?

A
  1. Omeprazole
  2. Lansoprazole
  3. Pantoprazole
  4. Rabeprazole

PPIs should be taken before a meal and really before the first meal of the day bc they work best when the parietal cell is stimulated to secrete acid in response to a meal.

May take 2-3 days til full effectiveness

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8
Q

Comparing H2Rs to PPIs, which works better?

A

PPIs work better bc it keeps acid secretion suppressed pretty much all day except for a mild increase in the early morning hours.

H2Rs does lower the acid a bit t/o the day, however it is really good at keeping the acid suppressed during the nocturnal hours.

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9
Q

What are PPIs used for? Adverse effects? Drug Interactions?

A

Used for GERD and Peptic Ulcers (better than H2R Antagonists); Zollinger-Ellison Syndrome; NSAID ulcers

Adverse Effects: HA, N/V, diarrhea

Interactions: Decreases absorption of things that require acid for absorption, ie Iron, B12, Digoxin; Binds CyP450 so clearance of warfarin, phenytoin, and benzodiazepines is reduced

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10
Q

What are the three mucosal protective agents and what is there MOA?

A

Sucrulfate: A pro-drug that at pH 4 becomes a viscous gel that coats ulcers better than native mucosa that becomes a physical barrier to acid and pepsin. TAKE ON EMPTY STOMACH 1 HR B4 MEALS 4X/DAY. Constipation :(

  1. Bismuth Colloidal Compounds aka Pepto Bismol: Enhances mucus and HCO3 secretion; direct antibacterial action; sequesters enterotoxins
  2. Misoprostol: Reduces ulcers in ppl who take NSAIDs. PGE1 ANALOGUE.
    • Acts on EP3 receptors
    • Inhibit gastric secretion
    • Enhance mucus and HCO3 secretion
    • Only for NSAID ulcers
    • NOT FOR PREGGOS
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11
Q

How are NSAID ulcers managed?

A

With Misoprostol (SEs are significant: diarrhea, n/v, bloating, pain),

PPIs esp when used with Misoprostol, or

COXibs (COX2 Inhibitors) such as celebrex to replace the NSAID, but with these the thrombogenic potential is increased

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12
Q

How to treat H. Pylori Infection?

A

Triple therapy for 2 weeks.

BMT: Bismuth, Metronidazole, Tetracycline
LAC: Lansoprazole, Ammoxicillin, Clarithromycin
OAC: Omeprazole, Ammoxicillin, Clarithromycin
RBC-AC: Ranitidine-Bismuth Citrate, Ammox, Clarithromycin
MOC: Metronidazole, Omeprazole, Clarithromycin

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13
Q

What is gastroparesis?

What is diabetic gastroparesis?

What type of drugs treat gastroparesis

A

Gastroparesis is delayed stomach emptying with partial paralysis of stomach. Food is prevented from getting to duodenum.

Diabetic gastroparesis is the same thing but in diabetic patients and is most common cause of this condition. 60%

Prokinetic drugs treat this

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14
Q

What is the pathogenesis of gastroparesis?

A

Dysfunctional NO neurons

Abnormal Interstitial cells of Cajal

Abnormal GI hormones ie motilin

Pylorospasm

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15
Q

What are the prokinetic drugs and what is their class, and what are they used for specifically?

A

Drugs:
Metoclopramide…5HT receptor modulator…GERD &Gastroparesis

Domperidone…Dopamine Rec Inhib…Not approved in US

Erythromycin…Motilin like agents…DIABETIC GASTROPARESIS

These drugs increase LES tone, and antral and SI contractions. Also the point of these drugs are to block dopamine from acting on neuron on myenteric plexus, and increase Ach acting on it.

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16
Q

What is IBS and what is the therapeutic strategy?

A

It is irritable bowel syndrome and affects 15% of US. Relapsing ab discomfort (pain, bloating, distension, cramps) accompanied with diarrhea, constipation or both.

Therapy is tailored to the individual

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17
Q

How is IBS managed?

A

Stool softener: DOCUSATE

Anti-spasmodics (anti-cholinergics): DICYCLOMINE (bentyl) and HYOSCYAMINE (Levsin)

5HT Antags: ALOSETRON (Lotrenex)

- blocks 5HT in vagal afferents and suppress vasomotor response to stomach distention.
- Approved for women with severe diarrhea predominant IBS
- Bad SEs...ischemic colitis and really bad CONSTIPATION
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18
Q

What is DOCUSATE and what is it used for?

A

It is a stool softener used for IBS

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19
Q

What is Dicyclomine and what is it used for?

A

It is an antispasmodic that is used for IBS

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20
Q

What is Hyoscyamine and what is it used for?

A

It is an antispasmodic that is used for IBS

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21
Q

What is Alosetron and what is it used for? Any significant SEs?

A

It is a 5HT receptor antag in vagal afferents that suppresses vasomotor response to stomach distention that is used in IBS.

Approved for women with diarrhea IBS

Bad SEs…ischemic colitis and bad constipation

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22
Q

What is Odansetron, its drug class, and its therapeutic use?

A

It is an anti n/v drug that is a 5HT rec Antag used for n/v due to chemotherapy

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23
Q

What is Granisetron, drug class, therapeutic use?

A

It is an anti n/v drug that is a 5HT rec Antag used for n/v due to chemotherapy

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24
What is Metoclopramide, drug class, therapeutic use?
It is an anti n/v centrally acting DOPAMINE receptor ANTAG used for vomiting due to chemotherapy, and n/v in general
25
What is Chlorpromazine, drug class, and therapeutic use?
It is an anti n/v centrally acting DOPAMINE receptor ANTAG used for vomiting due to chemotherapy, and n/v in general
26
What is Dronabinol, drug class, and therapeutic use?
It is an anti n/v drug that is a Cannabinoid receptor Agonist for vomiting due to chemo
27
What is scopalamine, drug class, and therapeutic use?
It is an anti n/v drug that is a muscarinic receptor antagonist used for motion sickness
28
What is Cyclizine, drug class, and therapeutic use?
It is an anti n/v drug that is a Histamine H1 receptor ANTAGONIST used for motion sickness
29
What is Dimenhydrinate, drug class, therapeutic use?
It is an anti n/v drug that is a Histamine H1 receptor ANTAGONIST used for motion sickness
30
What is Promethazine, drug class, therapeutic use?
It is an anti n/v drug that is a Histamine H1 receptor ANTAGONIST used for motion sickness
31
For Level 1 Emetics, what are the drugs used for acute emesis? Delayed Emesis?
Acute: None Delayed: MPLDD Metoclopramide, Phenothiazine, Lorazeppam, Dronabinol, Diphenhydramine
32
For Level 2 Emetics, what are the drugs used for acute emesis? Delayed Emesis?
Acute: One of these...Metoclopramide, Phenothiazine, Dexamethasone Delayed: MPLDD (my poo likes doo doo) Metoclopramide, Phenothiazine, Lorazepam, Dronabinol, Diphenhydramine
33
For Level 3/4 Emetics, what are the drugs used for acute emesis? Delayed Emesis?
Acute: A 5HT Antag like Ondansetron with Dexamethasone Delayed: MPLDD Metaclopramide, Phenothiazine, Lorazepam, Dronabinol, Diphenhydramine
34
For Level 5 Emetics, what are the drugs used for acute emesis? Delayed Emesis?
Acute: 5HT Receptor Antag (ie Ondansetron) with Dexamethasone with Substance P antagonist ie Aprepitant (blocks Neurokinin 1 Receptor) So 5HT Antag, Dexamethasone, Substance P Antag Delayed: Dexamethasone with one of these: -Ondansetron, Metoclopramide, Aprepitant
35
What is UC (ulcerative colitis)?
It is a chronic and superficial inflammation of distal colon that progresses to proximal colon. Only in colon!
36
What is Crohn's disease?
It affects both the LARGE AND SMALL BOWEL (as opposed to UC which just affects the large bowel). Inflammation is focused in one area, but can affect all layers of the GI tract (unlike UC which is superficial)
37
What are the two aminosalicylates?
They end in salazine... Sulfasalazine and Olsalazine
38
What are the two thiopurines?
Azathioprine and 6 mercatopurine
39
What is Infliximab?
It's a chimeric anti TNF monoclonal Ab
40
What kind of drug is Methotrexate?
It's an anti inflammatory
41
What cell does Cyclosporine A suppress?
It's for T cell suppression
42
5- Amino Salicylates are a family of compounds that are divided into Azo and Mesalamine compunds. What is the MOA of each and what are their respective drugs?
Azo: In term Ileum and colon, normal flora bacteria cleave Azo bond with AZOREDUCTASE ENZYME, which releases the 5-ASA compound. SULFASALZINE, OLSALAZINE, BALSALAZIDE Most people can't tolerate sulfasalazine ``` Mesalamine: Deliver 5-ASAs to various parts of the small and large bowel. PENTESA (s. intestine) Asacol (distal ileum, proximal colon), Rowasa (sigmoid colon) Canasa (rectum) ```
43
How are glucocorticoids useful in IBD? Drugs?
They inhibit inflammatory mediators, reduce inflammatory cell adhesion molecules. Use with MODERATE inflamm bowel disease, NOT FOR MAINTAINING REMISSION Drugs: Hydrocortisone enemas Budesonide (controlled release) Prednisone or Prednisolone Bisphosphonates also co-prescribed to avoid osteopenia
44
The thiopurines are used for IBD. What are the drugs, the MOA, SEs?
6-Mercaptopurine and Azothiopurine. -Azothiopurine is first metabolized in liver to 6-Mercaptopurine. Then both are metab'd to 6-thioguanine nucleotides. MOA: Induce T cell apoptosis, 6-18 weeks after surgery Used for moderate to severe IBD SEs: **Have to have routine lab monitoring** (CBC, LFT) Causes n/v hepatic toxicity, Blood (leukopenia, macrocytosis, anemia, thrombocytopenia, lymphoma)
45
What is the MOA for the Thiopurines?
Immunomodulation by T cell suppression. Effective 6-18 weeks after start. Used for moderate to severe IBD. 6-Mercaptopurine and Azothiopurine
46
What is the MOA of infliximab?
Binds to TNF-a: prevents it from binding to its receptor neutralizes its activity
47
What is Infliximab used to treat?
It's used to treat severe Crohn's disease, esp with fistulas, and UC. Given IV
48
What are the SEs of Infliximab?
Anaphylaxis (after multiple infusions) reactivation of TB (remember TNF-a keeps TB roped off) Contraindicated in infections
49
What is methotrexate and what is it used for?
It inhibits Dihydrofolate Reductase, so no folate for thymidine synthesis At high doses it has an anti proliferative effect Anti-inflammatory Methotrexate is used to maintain remission of Crohn's disease
50
What is the adverse effect of Methotrexate?
``` At high doses, causes... bone marrow depression Megaloblastic anemia Alopecia Mucositis ``` At low doses none of these SEs are present. Give folate supplements to prevent SEs w/o affecting the anti-inflam effect.
51
What are the most effective anti-diarrheal drugs?
Opiods and their derivatives bc they have maximal anti-diarrheal effect and minimal CNS effect Derivatives: Diphenoxylate and loperamide (weak analgesic effects) Kaopectate: absorbs bacterial toxins and fluid, decrease stool liquidity But these can cause constipation and interfere with other drug absorption
52
What is the clinical def of diarrhea?
Stool weight that exceeds 200g in 24 hours
53
What is acute diarrhea? Chronic?
Acute: 4 weeks
54
What are the types of diarrhea?
Secretory: ie cholera toxin Osmotic: ie when too much water drawn into bowels, ie high sugar or salt drinks Inflammatory: Passive loss of protein rich fluids, ie infections Motility Syndromes: food moves to quickly...vagotomy/hyperthryoid Decreased absorption surface: surgically removed bowel
55
On the bristol stool chart, what types are diarrhea classified as?
Types 5-7
56
How do you manage diarrhea? Hint there are 3 main ways...
1. Fluid and e-lyte replacement...Pedialyte/Infalyte 2. Anti microbial and anti-inflamm therapy 3. Symptomatic Therapy Intraluminal agents: Hydroscopic-->Kaopectate Bismuth-->PeptoBismol Anti-motility and anti-secretory agents u-opiod receptor blockers-->Loperamide, Diphenoxylate
57
Antibiotics are good for treating diarrhea. What drug would you give for Cholera? Shigella?, Campy? Giardiasis? Amebic dysentery?
``` Cholera: Doxycycline Shigella: Cipro Campy: Cipro Giardiasis: Metronidazole Amebic: Metronidazole ``` For most other germ caused diarrhea, just give symptomatic treatment. However there is a such thing as antiBx induced diarrhea. C. diff with clari
58
For symptomatic therapy of diarrhea what drug would you give for mild chronic diarrhea, what is the MOA of these drugs?
Give Kaolin & Pectate (Kaopectate). They bind water and toxins. Hydroscopic drug
59
For symptomatic diarrhea, what would you give for travelers diarrhea, anal incontinence, or IBD?
Give Loperamide (OTC) or Diphenoxylate. These drugs slow the mouth to cecum time, increases anal tone, and anti-secretory against bacterial toxins. They are u-opiod receptor agonists
60
Laxatives What is the mechanism for Psyllium, methylcellulose, polycarbophil?
Bulk forming
61
Laxatives What is the MOA for DOCUSATE, GLYCERIN, MINERAL OIL?
Stool softening
62
Laxatives What is the MOA of Mg Oxide, Sorbitol, Lactulose, Mg Citrate, NaPO4, polyethylene glycol?
Osmotic
63
Laxatives What is the MOA for Aloe, senna, cascara, castor oil, bisacodyl?
Stimulant
64
Laxative What is the MOA of Lubiprostone. (Hint sounds like lube...think water. what channel causes water release)
Cl- channel activator
65
Laxatives What is the MOA of Methylnaltrexone and Alvimopan
Opiod receptor antagonists
66
Laxatives What is the MOA of Tegaserod?
5HT receptor agonist
67
How is steatorrhea relieved?
Relieved by pancreatic lipase supplementation (oral)
68
What is pancrelipase and what is it used for?
It is used for pancreatic insufficiency: ie in CF, chronic pancreatitis, pancreatic resection Its a mixture of pancreatic enzymes incl amylase, lipase, proteases Bc its inactivated by gastric acid, its coated. If its not coated, has to be given with a PPI Used to treat steatorrhea, malabsorption of lipid solube vitamins, and B12, weight loss
69
What is URSODEOXYCHOLIC ACID and what is it used for?
It is an oral drug that is a naturally occuring bile acid that inhibits gallstone formation. Decreases cholesterol content of bile by hepatic cholesterol synthesis. Stabilizes hepatocyte canicular membranes This is for patients with gallstones WHO REFUSE SURGERY. Also prevents formation of gallstones in obese patients Minimal SEs

Pharmacology (17 decks)

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