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MODHIII - Unit 3 > GI Drugs > Flashcards

Flashcards in GI Drugs Deck (75)
1

Routes of acid stimulation

- histamine: from ECL cells
- gastrin: from G cells
- acetylcholine: nervous system (vagus nerve)

2

Histamine stimulated acid release is inhibited by

protanoids

3

Histamine acts on what receptor on parietal cell

H2

4

How is acid pumped into the stomach from parietal cells

K+/H+ ATPase antiporter

5

Proton Pump Inhibitors (PPIs): drugs

- Omeprazole
- Esomeprazole
- Lansoprazole

6

PPIs activation

- all are prodrugs that require acid activation

7

PPIs: action

- IRREVERSIBLY inhibit the proton pump
- enter parietal cells from the systemic circulation & activated withing the acidic environment around proton pump
- ineffective if activated in stomach by acid so they are put in gelatin capsules, coated, mixed with bicarb, or given parenterally

8

PPIs: administration

- gelatin capsules (omeprazole, esomperazole, lasoprazole)
- enteric coated tablets (pantoprazole, rabeprazole, omeprazole)
- mixed w/ bicarb (omeprazole)
- pantoprazole and lansoprazole can be give parenterally

9

PPIs: dose

- dosed daily
- active for about 2 hours but therapy relies on slow turnover of K+/H+ ATPase at the apical surface

10

PPIs: uses

- lower acid secretion 90%
- GERD, erosive esophagitis, peptic ulcers, zollinger-ellison syndrome, NSAID induced gastric ulcers, part of H. pylori treatment

11

PPIs: clearance

LIVER

12

PPIs: activity of proton pumps

- not all proton pumps are active at any one time
- only those that are active react with these drugs
- treatment requires 2-5 days

13

PPIs: adverse reactions

- nausea, abdominal pain, constipation, flatulence, diarrhea
- drug interactions through altered CYP activity: increase serum WARFARIN concentrations, decrease activation of clopidogrel

14

H2 receptor antagonists: drugs & duration

- cimetidine: 4-5 hrs
- ranitidine: 6-8 hrs
- famotidine: 10-12 hrs

15

H2 receptor antagonists: process and use

- block base level of acid secretion maintained by ECL cells
- use: NOCTURNAL acid secretion, duodenal ulcers, zollinger-ellison

16

H2 receptor antagonists: effectiveness

- decrease acid secretion 70% for 24 hours with daily dosing

17

H2 receptor antagonists: excretion

- RENAL via organic cation system

18

H2 receptor antagonists: adverse reactions

-

19

H2 receptor antagonists: adverse effects of cimetidine

- long term use of cimetidine at high doses decreases testosterone binding to androgen receptor and hydroxylation of estradiol causing galactorrhea in women and decreased sperm count, impotence and gynecomastia in men

20

H2 receptor antagonists: tolerance

- tolerance can develop in 3 days due to direct acid stimulation by gastrin

21

Prostaglandin analogs: Misoprostol

- synthetic analog of PGE1
- short acting, up to 3 hrs
- use: NSAID induced injury (less than PPIs and H2 antagonists though)
- adverse: diarrhea (30%), exacerbate IBD, increase uterine contractions

22

Sucralfate

- octasulfate of sucrose with Al(OH)3
- forms sticky neutral pH polymer coating that covers epithelium
- uses: stress ulcers (sticks better to duodenal than gastric ulcers)
- ACID activated, so take before food, and avoid antacids and PPIs
- adverse: constipation, block absorption of other drugs through stomach

23

Antacids: process & components

- neutralize pH of gastric contents
- Al(OH)3, Mg(OH)2, CaCO3 common components

24

Antacids: action

- fast acting: 15 min
- last up to 2-3 hours WITH food

25

Antacids: Mg vs. AL

Mg: fast acting, stimulates gastric emptying and motility
Al: slower acting, delays gastric emptying and slows motility

26

Antacids: gas

- surfactant simethicone is sometimes added to reduce gas

27

Antacids: adverse effects

- rebound acid secretion
- Mg contraindicated in RENAL disease
- interference with GI absorption of other drugs: take antacids 2 hrs before or after other drugs**********

28

Muscarinic antagonists

- pirenzepine: selective for M1 receptors
- blocks neurotransmission in ganglia resulting in less vagal stimulation of parietal and ECL cells
- reduce basal acid by 50%
- significant anticholinergic side effects

29

H. pylori infection

- 50% of all humans: 1/3 are pathogenic, difference is vacuolating endotoxin A
- associated with over half of peptic ulcer disease, gastritis, GERD
- bacteria need acid, which activates the toxin

30

H. pylori treatment

- combination of acid neutralization, cytoprotection, antibacterial agent

31

Gastrointestinal motility: process

- mechanical/chemical stimulation leads to serotonin release from enterochromaffin cells that stimulate primary afferent neurons
- ACh stimulates constriction (ORALLY), NO stimulates relaxation (ANALLY)
- uses myenteric plexus control of circular muscle

32

Tegaserod

- serotonin partial agonist
- used for females with irritable bowel syndrome

33

Cisparide

- 5-HT4 receptor agonist and adenylate cyclase stimulant
- used for GERD and gastroparesis

34

Adverse reactions of tegaserod & cisapride

- fatal cardiac arrhythmias
- only available through restricted distribution programs administered by FDA or manufacturer

35

Bethanechol

- cholinergic derivative
- used to help urination in post surgical patients
- aim is to selectively activate M2 and M3
- side effects: bradycardia, flushing, diarrhea, cramps, salivation, blurred vision

36

Neostigmine methylsulfate

- acetylcholinesterase inhibitor
- used to counter an ILEUS

37

Metoclopramide

- dopamine receptor antagonists (enhance normal ACh response)
- increases LES tone and upper GI motility
- can relieve symptoms of GERD but does not promote healing
- uses: nausea, vomiting in dysmotility syndromes and as an antiemetic
adverse: extrapyramidal effects, dystonias, parkinson like symptoms, tardive dyskenesia with chronic use

38

Motilin activity

- motilin is a peptide hormone that amplifies motor activity through effects on enteric neurons and smooth muscle
- secreted by enterochromaffin cells and M cells in upper small bowel

39

Erythromycin and other "mycin's"

- imitate motilin
- macrolide antibiotics
- cause gastric dumping which can move bezoars, improve gastric emptying with ileus, scleroderma, pseudo-obstructions
- fast dumps can be painful, no recommended for chronic use

40

When is diarrhea necessary

- cholera and shigellosis

41

Laxation

- evacuation of formed fecal material from the rectum

42

Catharsis

- uniform evacuation of material from the entire colon (watery
- many cathartics produce laxation at low dosages

43

Mechanisms of laxatives

- prokinetic agents
- bulk forming agents increase mechanical efficiency
- wetting agents, osmotic, irritants

44

Osmotic laxatives: process

- non absorbable agents
- cause water retention
- really cathartics causing bowel emptying with watery stool, but act as laxatives at lower dosage

45

Osmotic laxatives: types

- alcohols: polyethylene glycol (mcdonalds shakes)
- salts: magnesium hydroxide (Milk of Magnesia), other Mg salts
- sugars: lactulose, sorbitol, mannitol

46

Osmotic laxatives: Mg

- may stimulate CCK receptors and increase motility
- should be avoided in individuals with renal insufficiency, cardiac disease, electrolyte abnormalities, or with diuretic use

47

Osmotic laxatives: sugars

- lactulose, sorbitol, mannitol
- used for constipation with opioid use and vincristine
- bacterial fermentation of lactulose also drops luminal pH and can trap NH4 (increased in colon of patients with severe hepatic disease)

48

Glycerin

- suppository that acts as a hydroscopic agent and lubricant
- increase water retention stimulates peristalsis producing evacuation reflex
- rectal administration can produce a bowel movement within an hour

49

Stool wetting agents

- docusate salts
- surfactants that allow mixing of fatty substances and water in stool
- do not increase frequency of defecation just soften stool

50

Irritant laxatives

- bisacodyl: orally or rectally
- induce moderate inflammation leading to reduced water absorption and increased motility
- safe but overdose causes catharsis
- don't chew tablets or mix with milk or antacids to ensure tablet reaches site of action in small intestine and avoid gastric irritation*******

51

Castor oil

- smooth muscle stimulant: used as laxative, catharsis, induce labor
- made from ricinus communis (castor bean): produces ricin (toxic) and oil ricinoleic acid (not toxic)
- speeds motility in small bowel
- 4 ml for laxative effect in four hours, 16ml for cathartic effect

52

Bulk forming laxatives

- fiber based: material not broken down, material stimulates peristalsis
- examples: methylcellulose, psyllium, polycarbophil
- great for regular soft stools
- adverse: exacerbate intestinal obstructions, absorption of other drugs

53

Mechanism of antidiarrheal agents

- bulk forming agents: reduce fluidity without reducing water content
- opioids: reduce motility to increase transit time and water absorption
- octreotide: reduce secretions

54

Antidiarrheal: bulk forming agents

- based on colloids or polymers
- absorb water within GI tract to decrease stool fluidity
- only provides symptomatic relief

55

Diphenoxylate & difenoxin

- opioid
- difenoxin is the active metabolite of diphenoxylate
- piperidine derivatives
- can have CNS effects**packaged with atropine to discourage abuse**

56

Loperamide

- opioid
- 40-50X more potent than morphine
- does not enter CNS

57

Paregoric

- opioid
- has 2mg morphine per 5 ml
- adults 5-10 ml, 1-4 doses daily; children .25-.5mg/kg/dose

58

Octreotide: uses, adverse

- somatostatin derivative
- use: combat secretory diarrhea of hormone secreting tumors, post surgical gastric dumping syndrome and diarrhea associated with chemo, rest the pancreas with pancreatitis
- adverse: nausea, bloating, injection site pain; long term therapy may result in gallstones

59

Bismuth subsalicylate (Pepto Bismol)

- bismuth: 99% unabsorbed and eliminated in feces, anti secretory, anti inflammatory, anti microbial, commonly included in H. pylori treatments
- salicylate: released in acidic stomach, NSAID activity absorbed systemically
- Mg aluminum silicate (clay): bulk forming effects

60

Irritable bowel syndrome: process and symptoms

- NON-inflammatory bowel disorder
- characterized by chronic abdominal pain and bloating w/ alternating constipation/diarrhea

61

Irritable bowel syndrome: treatment

- alosetron: 5HT3 antagonist use for diarrhea predominant IBS; produces effects opposite of 5HT4 agonists, also reducing visceral sensitivity by reducing vagal nerve signaling; can produce serious constipation and potentially FATAL ischemic colitis
- tegaserod: 5HT4 agonist used for constipation predominant IBS

62

Emesis

- controlled centrally by chemoreceptor trigger zone (CTZ) in fourth ventricle and can sense both spinal fluid and blood; solitary tract nucleus (STN) of the vagus nerve
- peripheral input: senses, inner ear, small intestine, pharynx

63

Antiemetics: serotonin receptor (5HT3) antagonists

- serotonin promotes gut motility
- act centrally at the CTZ and the STN
- act peripherally in small intestine
- use: chemo induced emesis and nausea
- Ondansetron is prototype of the class

64

5-HT3 antagonist

- ondasetron: 3.9 hrs
- granistron: 9-11.6 hrs
- dolasetron: 7-9 hrs
- palonosetron: 40 hrs; highest affinity for receptor in this class

65

5-HT3 antagonists: adverse reactions

- constipation, diarrhea, headache, light headedness

66

Dopamine receptor antagonists

- metoclopramide
- some antagonism of 5-HT3
- effects CTZ, also increase forward motility; stops emesis promotes defecation
- preferred agent for chemo induced nausea

67

Dopamine receptor antagonists: phenothiazines

- prochlorperazine, chlorpromazine
- preferred for general anti nauseants & anti emetics
- targets D2 receptors in CTZ, and H1 receptors
- good for motion sickness (H1 effects)

68

Dopamine receptor antagonists: adverse reactions

- parkinson like symptoms, extrapyramidal side effects
- may cause dissociative dysphoria in psychiatrically normal patients

69

Antiemetic: antihistamines

- H1 receptor antagonists
- use: motion sickness, post op emesis
- acts on brainstem and vestibular apparatus

70

Antihistamine: drugs

- cyclizine, promethazine, hydroxyzine: act on STN
- diphenhydramine: act on cerebellum
- cyclizine also has anticholinergic effects used in patients with abdominal cancer

71

Anticholinergics: process

- muscarinic ACh receptor antagonists
- scopolamine can be sued parenterally, more commonly trans dermal
- effective short or long term prevention of motion sickness
- acts on vestibular apparatus
- not effective for chemo induced nausea, minimal CTZ effects

72

Anticholinergics: adverse effects

- dry mouth, blurred vision
- outbursts of uncontrolled behavior when used in presence of pain or anxiety

73

Syrup of ipecac

- given orally shortly after ingesting toxin/drug
- acts on CTZ
- superseded by activated charcoal, b/c of danger of aspiration

74

Apomorphine

- D2 agonists, acts locally and on CTZ
- given sub-Q
- largely superseded by activated charcoal
- used more in veterinary medicine

75

Most potent stimulator for acid release

Gastrin