Gi Drugs - Part Of Pharm Exam 2

Front 1

Describe some functions of the GI tract, and the cells which perform them.

Back 1

* GI Tract
o Barrier Function – gastric acid, colonization resistance, mucosal defenses; immune system (body’s largest immune organ): inductive (GALT - GI associated lymphoid tissue) and effector sites
o Epithelial cells – parietal cells, chief cells, G-cells; absorptive, goblet, Paneth, entero-endocrine cell types - they make specific hormones and secretion
o Enteric nervous system – motility, exocrine/endocrine secretion, microcirculation
o Lumen of GI tract is technically outside of the body, not at all sterile inside



Specialized cells that sample antigens going through GI tract and prepare for possible immune response; also special cells that sample GI gract and secrete hormones and signals to break down more or less carbs etc.

Front 2

When you have a patient with a GI disorder, what is often the first infection that patients get?

Back 2

- Pneumonia

Front 3

In the stomach, how are the parietal cells triggered/stimulated?

Back 3

- Signals from vagus nerve (muscarinic receptors for AcH)
- Histamine (histamine receptor)
- Gastrin that the G cells are making
- Somatostatin - the only inhibitory one

Front 4

Name the two types of GI disorders, with examples.

Back 4

o Organic Disorders – GERD, PUD, Pancreatitis, Cirrhosis, IBD, …
+ structural disorders - the ones that you can actually see if you look at the GI tract
o Functional Disorders – esophageal (e.g., achalasia - food swallowed but doesn’t move in the GI Tract), gastroduodenal (e.g., non-ulcer dyspepsia), bowel (e.g., irritable bowel syndrome), biliary (e.g., biliary dyskinesia), anorectal (e.g., fecal incontinence)

Front 5

Describe the physiology of nausia and vomiting, including the NTs used to trigger it.

Back 5

o Management depends in part on etiology
+ Why are they n/v? - having an MI? Infection? medication? toxin?
o General
+ Interrupt physiologic pathways into emetic center
+ Involves several neurotransmitters (central, peripheral)
# Acetylcholine (M), dopamine (D), histamine (H), neurokinin (NK), serotonin (5-HT)

Front 6

What stimulates The n/v center in your brain?

Back 6

o Sensory input: sight smaell, pain
o Vestibular apparatus
o Blood borne emetics: Chemotherapy, opiods, Ipecac
o Stomach and small intestine - serotonin and dopamine
o Higher centers: - fear, anticipation

Front 7

Ondansetron (Zofran®)

Back 7

Therapeutic Use – prevention of nausea & vomiting

Dose (4-11 yo) – 4 mg tid prn (PO), 50-150 μg/kg (IV)

Dose (>12 yo) – 8 mg tid prn (PO), 50-150 μg/kg (IV)

Forms – injection (2 mg/mL), tabs (4*, 8*, 24 mg), and an oral soln (4 mg/5 mL)

Elimination – hepatic (CYP1A2, -2D6, -2E1, -3A4)

Adverse Effect – headache, seizures - be careful with pts. who have a hx of this - lightheadedness, constipation/diarrhea b/c it acts as a serotonin blocker; there are a lot of difft serotonin receptors in GI, so depending on their various concentrations, it will have different effects on different people, transient LFT (liver function tests) increases

Front 8

Metoclopramide (Reglan®, others)

Back 8

Therapeutic Use – emesis, dysmotility - tightens up sphincter, increases stomach contractility etc.; it’s a dopamine antagonist

Dose (child) – 0.1-0.2 mg/kg AC q6-8h (PO, IV)

Dose (>14 yo) – 10 mg q6-8h (PO, IV)

Duration – t½ ~ 5-10 h

Elimination – renal

Adverse Effect – sedation, headache, anxiety, depression, EPRs (looks like parkinson’s), leukopenia, hypotension, diarrhea (contains sugars, creates osmotic effect into GI tract)

Caution – GI obstruction, seizures

Front 9

What factors can cause constipation?

Back 9

+ Lifestyle issues (fluid intake, food intake, immobility)
+ External factors (e.g., medication)
+ Internal factors (e.g., endocrine, neurologic)

Front 10

When managing constipation, are laxatives first or second line drugs?

Back 10

- second line, because you want to treat the Cause of the constipation first.

Front 11

What are the different types of non-specific laxatives?

Back 11

* Bulk-forming – methylcellulose, polycarbophil, psyllium - maintanance effect
* Surfactant – docusate - make it slippery; (a lot of people use these when pt. is on opiods, but opiods afect GI motility, and surfactant doesn’t help at all - longer term effect
* Stimulant – bisacodyl, senna - kickin over 6-8 hours
* Osmotic – magnesium salts, phosphate salts, sorbitol

Front 12

Alvimopan (Entereg®)

Back 12

Indication – management of opioid-induced bowel dysfunction (including post-op ileus, constipation) - the opiod paralizes GI tract

Mechanism – peripheral MOP receptor antagonist

Dose – 0.5-6 mg daily

Adverse effects – abdominal discomfort and pain, flatulence, diarrhea; anemia, hypokalemia, back pain, urinary retention; Caution: severe hepatic impairement, ESRD
- this is one of the specific laxatives

Front 13

What are the different types of specific laxatives?

Back 13

* 5HT agonists – tegaserod (Zelnorm®)
* Cl- channel activator – lubiprostone (Amitiza®)
* Opioid antagonists – alvimopan (Entereg®), methylnaltrexone (Relistor®)

Front 14

Lubiprostone (Amitiza®)

Back 14

Indication – chronic idiopathic constipation

Mechanism – chloride-channel activator - (leads to chloride pouring into tract along with sodium which pulls water in)

Dose – 24 μg BID with food

Onset/Duration – effective at one week; pts. may need to take it on a regular bassis to be effective

Elimination – reduction & oxidation - technically, the drug isn’t ever absorbed into the body

Adverse effects – headache, nausea, abdominal pain, distension, diarrhea; caution avoid if GI obstruction or severe diarrhea, avoid in pregnancy

Front 15

What causes diarrhea

Back 15

nfection (usually viral 80% of the time, also bacterial and paracitic), surgical (appendicitis, obstruction), other (allergy, malabsorption)

Front 16

What are the priorities of treatment in cases of diarrhea?

Back 16

+ Address any infection control issue or malabsorption
+ Fluid & electrolyte repletion - this is the priority
# Oral
# Intravenous

Front 17

list the different antidiarrheal agents.

Back 17

- not recommended for acute diarrhea esp if caused by bacteria, b/c you’re just blocking it in to multiply and grow

# Bulk agents – attapulgite, methylcellulose, polycarbophil, psyllium

# Anticholinergics – dicyclomine (Bentyl®), hyoscyamine (Levsin®)
# Antimotility agents – diphenoxylate/atropine (Lomotil®), loperamide (Imodium®),
# Antisecretory agents – bismuth subsalicylate, crofelemer, octreotide,
# 5HT antagonists – alosetron (Lotronex®)
# Anti-infective agents –

Front 18

Loperamide (Imodium®, others)

Back 18

Indication – diarrhea (once infection has been ruled out!); high output ileostomy

Mechanism – opioid agonist at the GI tract

Dose – 4 mg initially, 2 mg following each loose stool … or 30 min AC … (max 16 mg per day) - hard ceiling. don’t take any more than this

Onset – within a few hours - take it ½ to one hour before eating

Elimination – limited enterohepatic recirculation; excreted in feces

Adverse effects – NV, dry mouth, abd discomfort, constipation; avoid if infectious etiology suspected (b/c then you’re just blocking it in to grow)

Front 19

Alosetron (Lotronex®)

Back 19

Indication – severe diarrhea-predominant IBS in women

Mechanism – 5HT3-receptor antagonist

Dose – 1 mg daily x 4 wks, re-assess; (1 mg bid max)

Elimination – metabolized by CYP (2C9>3A4>1A2); excreted predominantly in urine

Adverse effects – nausea, abd discomfort, constipation; avoid if h/o IBD, constipation, obstruction, stricture, adhesions, ischemic bowel (BAD, then your bowel dies... don’t use it if possible), hypercoagulable state; caution ischemic colitis, constipation

Front 20

Dicyclomine (Bentyl®, others)

Back 20

Indication – pain assoc with functional bowel disorder

Mechanism – (anticholinergic) muscarinic receptor antagonist at enteric plexus and smooth muscle

Dose – 10-20 mg q4-6h prn (take just before meal)

Adverse effects – dry mouth, visual disturbances, urinary retention, constipation (anticholinergic effects); interaction with other anticholinergic agents

Front 21

Probiotics

Back 21

o For prevention and treatment of diarrhea, IBD, other
o To prevent unballance in GI tract
o Live micro-organisms – Lactobacilli, Bifidobacterium, Saccharomyces
o Administered into the GI tract
o Rare complications

Front 22

What is GERD and what causes it?

Back 22

o GERD = gastro-esophageal reflux disease

* Symptoms reported to occur monthly in ~44%
* Rare mortality, but greatly diminished QOL


* Symptomatic condition or histologic change associated with retrograde movement of gastric contents to esophagus
* Clinical Presentation of GERD
* Some foods/meds may worsen GERD symptoms

Front 23

What are the consequences of chronic GERD?

Back 23

o Reflux esophagitis
o Erosive esophagitis - eventually the cells can become pre-cancerous
o Complications – strictures, Barrett’s esophagus, adenocarcinoma

Front 24

What is PUD?

Back 24

* PUD = peptic ulcer disease

* Most significant acid-related disorder
* 10% develop during lifetime, recurrence is frequent
* Mortality with gastric ulcer > duodenal ulcer
* It’s caused by infection

Front 25

Where are ulcers found?

Back 25

o Gastric ulcer (GU)
o Duodenal ulcer (DU)
o Other sites

Front 26

What is the etiology of PUD?

Back 26

* Etiology
o Common Causes
+ Helicobacter pylori (HP) infection
+ Non-steroidal anti-inflammatory drugs (NSAIDs)
+ Critical illness stress-related mucosal damage (SRMD)
o Uncommon Causes
+ Gastric acid hypersecretion (e.g., Zollinger-Ellison)
+ Viral infection (e.g., CMV)
+ Vascular insufficiency
+ Radiation; rarely chemotherapy
+ Genetic; Idiopathic

Front 27

How does chronic PUD present clinically?

Back 27

o Symptoms
+ Abdominal pain (epigastric, burning, fullness, cramping)
+ Nocturnal pain (awakening patient from sleep)
+ Episodic (seasonal, intermittent)
+ Change in character of pain may suggest complication
+ Heartburn, belching, bloating often accompany pain
+ Anorexia, nausea, vomiting (gastric > duodenal)
o Signs
+ Weight loss
+ Complications (bleeding ulcer, perforation, obstruction)

Front 28

How do you test for chronic PUD?

Back 28

o Lab tests
+ Tests for H. pylori
+ Hematocrit, hemoglobin, and stool hemoccult
+ Gastric acid secretion studies
+ Fasting serum gastrin (in patients unresponsive to therapy)
o Other
+ EGD for inspection and biopsy
+ Barium-contrast studies

Front 29

What is the therapy for GERD at different phase levels?

Back 29

Phase I = Intermittent, mild heartburn
* Lifestyle modifications PLUS
* Antacids AND/OR OTC doses of proton pump inhibitors or H2-antagonists


Phase II = For symptomatic relief

* Lifestyle modifications PLUS
* Standard dose proton pump inhibitors or H2-antagonists


Phase III = Healing of erosions or complications

* Lifestyle modifications PLUS
* Aggressive dose proton pump inhibitors or H2-antagonists

Front 30

How can you treat GERD?

Back 30

o Lifestyle changes
+ Elevate head of bed, dietary changes, weight reduction, smoking cessation, ethanol avoidance, avoid tight-fitting clothes, discontinue or use caution with influencing meds
o Over-the-counter self-treatment
o Standard dose histamine receptor-2 antagonists (H2As) or proton pump inhibitors (PPIs)
o Surgery

Front 31

How do you treat PUD?

Back 31

o Lifestyle changes; surgery
o Medications
+ Eradicate H. pylori if present
+ Discontinue NSAID if possible, provide protection from NSAID

Front 32

Antacids

Back 32

MOA – maintains gastric pH > 4, thereby  pepsin

Advantage – inexpensive

Disadvantage – requires frequent administration

Dosing and Administration – 2 tablets or 15-30 mL after meals and bedtime

Contraindications – interacting medication (tetracyclines, iron, isoniazid, quinolones, sulfonylureas)

Adverse Effects – constipation (aluminum), diarrhea (magnesium)

Front 33

Proton Pump Inhibitors

Back 33

MOA – inhibits the H+-K+-ATP-ase “pump”; they are all prodrugs; need a very low pH to work; quite effective in reducing acid production

Advantage – superior to H2As in moderate-severe disease

Disadvantage – takes 3-4 d for full effect; drug degrades in acidic environment so must be enteric coated; metabolized by CYP2C19 and CYP3A4

Dosing and Administration – at high doses, benefit with BID dosing (15’ AC);

Adverse Effects – headache, dizziness, somnolence, GI complaints; myopathy and arthralgia, hypergastrinemia ( by supressing HCL production, more gastrin is pumped in to stimulate the cells to make HCL), vitamin B12 deficiency

Front 34

Omeprazole (Prilosec®)

Back 34

ndication – GERD, GU, DU, other hypersecretory states

Mechanism – reduces HCl secretion from parietal cells by inhibiting H+-K+-ATP-ase activity

Dose – 20-40 mg daily

Elimination – hepatic metabolism and renal excretion

Adverse effects – Headache, dizziness, somnolence, GI complaints; hypergastrinemia, vitamin B12 deficiency

Drug interactions: Dec absorption of ketoconazole b/c it needs acidic environment to be absorbed; decreased effect of clopidogrel b/c it needs CYP to be metabolized to it’s active form, but this drug uses it up

Front 35

Sucralfate (Carafate®)

Back 35

MOA – mucosal surface protection

Advantage – non-absorbed (Al-salt of sucrose-octasulfate)

Disadvantage – aluminum absorption possible in CKD patients

Dosing/Administration – take on empty stomach; 1 g qid (2 g bid)

Contraindications – avoid interaction with other meds (amitriptyline, digoxin, fluoroquinolones, ketoconazole (decreased absorption, because it needs acidic environment to be absorbed), warfarin)

Adverse Effects – dry mouth, nausea, constipation, hypophosphatemia

Front 36

Histamine2 Receptor Antagonists

Back 36

MOA – inhibit histamine-stimulated acid secretion

Advantage - symptomatic relief for most patients with GERD and non-HP or non-NSAID-induced PUD

Disadvantage – tolerance with continued dosing; CYP inhibition; poor protection from PUD rebleeding

Dosing and Administration – dose adjust in renal impairment

Contraindications – avoid interacting medication (cimetidine: nifedipine, phenytoin, propranolol, theophylline, warfarin)

Adverse Effects – headache, somnolence, fatigue, dizziness, constipation or diarrhea, (confusion, slurred speach, delirium, hallucination - esp for elderly)

Front 37

Ranitidine (Zantac®)

Back 37

Indication – GERD, GU, DU, other hypersecretory states
Mechanism – reduces HCl secretion from parietal cells by blocking H2 receptors
Dose – 150 mg bid, 300 mg hs (50 mg IV q8h)
Elimination – hepatic metabolism and renal excretion
Adverse effects – Headache, somnolence, fatigue, dizziness, constipation/diarrhea; rare confusion or other mental status changes; interactions weak inhibitor of drug-metabolizing enzymes; if you give it with an antiacid it’s bioavailability drops precipitously

Front 38

Sucralfate (Carafate®) - updated

Back 38

MOA – mucosal surface protection; doesn’t get absorbed, works in areas that are beginning to erode
Advantage – non-absorbed (Al-salt of sucrose-octasulfate)
Disadvantage – aluminum absorption possible in CKD patients; requires pH < 4 for optimal action ( so can’t take it with antacids)
Dosing/Administration – take on empty stomach; 1 g qid (2 g bid)
Contraindications – avoid interaction with other meds (amitriptyline, digoxin, fluoroquinolones, ketoconazole (decreased absorption, because it needs acidic environment to be absorbed), warfarin)
Adverse Effects – dry mouth, nausea, constipation, hypophosphatemia; caution in gastroparesis where not emptying stomach well, can form a ball and block tract