GI pharmacology Flashcards

1
Q

Targets of Antacids/treatment of ulcers

A

Regulation of acid secretion (H+) by parietal cells is controlled by the proton pump.

Muscarinic receptor (M), histamine receptor (H) and gastrin (G) receptor pathways all stimulate acid secretion.

Prostaglandin receptor (PG) pathways inhibit acid secretion.

M, H and G all work by G-protein coupled receptors. Coupled to adenylate cyclase–>increase cAMP–>stimulate proton pump to secrete acid.

PGs help protect gut by increasing blood flow, increasing mucus secretion, which also helps with bicarb buffering capacity.

nb: aside from targeting these receptor pathways, proton pump itself can be a target for drug action

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2
Q

Causes of ulcers

A

Drugs: NSAIDs, steroids- interfere with production of endogenous PGs- also, tend to use these types of drugs chronically

Shock, hypotension, trauma

bile reflux

metabolic diseases

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3
Q

Antacids

A

Aluminum salts (AlOH, carbonate, silicate) and Magensium salts (hydroxide, oxide, trisilicate)

These antacids are essentially alkaline chemicals that neutralize acids in stomach.

uses: adjuncts to H2 antagonists and proton pump inhibitors; non-specific therapy.

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4
Q

Mechanism and side effects of antacids

A

Mechanism: chemically neutralize gastric HCl; inhibit pepsin secretion (benefit: pepsin production is a stimulus for acid secretion); not absorbed systeimcally. H2O and neutral salt are passed out of GI tract

side effects:

rebound acid secretion: stomach neutralized, may start to produce more acid– this side effect is more common with magensium salts; wears off with use

constipation

impair absorption of other drugs- can interfere with function and absorption of other, more specific therapies.

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5
Q

Histamine receptor antagonists

A

e. g. cimetidine (tagamet) and ranitidine (zantac)
uses: gastritis, gastric ulcers, oesophagitis

Mechanism of action: competitive antagonism of H2 receptors in parietal cells

Pharmacokinetics: oral administration–>direct to action

widely distributed and well-absorbed; hepatic metabolism and renal excretion.

Not a huge number of side effects: H2 receptors are basically only in the stomach. NB: not licensed for use in animals, but widely used.

NB: cimetidine is able to induce synthesis of microsomal enzymes–> can impact use of other drugs.

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6
Q

Sucralfate

A

sucrose sulfate-aluminum hydroixde complex

Mechanism: polymerizes to viscous gel at pH < 4. forms long chains under acidic conditions–> polymerizes to gel–> exposed sulfate groups bind to protein in ulcerated tissue–>creates a bandage over the area.

Uses: tx of gastric and duodenal ulcers

Side effects: constipation- not absorbed from GI therefore low risk of systemic side effects. Give at least an hour apart from H2 antagonist.

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7
Q

Proton pump inhibitor

A

e. g. omeprazole (prilosec)
uses: gastritis, gastric ulcers, oesophagitis, prevention and treatment of ulcers caused by NSAIDs

Mechanism: inhibits H+/K+ ATPase pump on luminal membrane of parietal cells.

Binding is irreversible. Body has to synthesize new enzyme to create pump again–> long action, can give SID

NB: can also affect microsomal enzymes

oral administration

accumulates in parietal cells due to chemical make-up. the charged form of the molecuule is active–has selective action in parietal cells. Other ATPase that exists in body is largely unaffected, as charged forms can’t get through membranes.

Hepatic metabolism/renal excretion

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8
Q

PGE 2 analogues

A

e.g. misoprostol- methyl ester of PG–> very stable and long lasting

Can’t use PG itself because it’s not long-lasting/stable enough

PG analogue will decrease acid secretion, increase blood flow and increase mucus production.

Uses: prevention and treatment of ulcers caused by NSAIDS- working on same pathway can reduce detrimental effect. Commonly used in cats and dogs

Stable analogue of PGE2, agonist at PG receptor

Side effects: diarrhea

PG has critical role in repro cycle-> not good in pregnant animals or in animals who will be/might be pregnant in the future.

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9
Q

Control of vomiting

A

Stimuli from pharynx/stomach–> visceral afferents: 5HT3

visceral afferents–> Nucleus of solitary tract: H1, mACH

sensory afferents e.g. pain,sight, smells–> Higher centres

Motion–> Vestibular nuclei (H1, mACh)

visc. afferents and vestib inputs–>Chemoreceptor trigger zone (D2, 5HT3)

CTZ, Nucleus of solitary tract and higher centres–> Vomiting centre (mACh, NK-1)–> emesis

H1= histamine

D2=dopamine

5HT3= serotonin

mACh=muscarinic acetylcholine

NK-1= neurokinin 1

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10
Q

further control of vomiting

A

NK-1: neurokinin– substance P acts on NK-1 receptor (final gate in control of vomiting)

Vomiting centre has NK and mACh receptors. Dogs have H1 receptors in vomiting centre, but cats don’t.

Vomiting reflex well developed in carnivores and pigs; no vomiting reflex in equids, ruminants, rats or rabbits

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11
Q

Induction of vomiting- emetics

A

Emesis contraindicated if: unconscious, suscpetible to seizures, ingested corrosive, caustic or viscous material

nb: rat poisons work so effectively in rats because they can’t vomit

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12
Q

3% hydrogen peroxide- emetic

A

if higher than 3%, corrosive

Mechanism: stimulates visceral afferents; mild gastric irritant

Pharmacokinetics: oral admin

Uses: emetic in cats and dogs

no real side effects

5mg/kg

physical agitiation of walking helps mix around in stomach and stimulate afferents. 15-20 minutes time to action.

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13
Q

Ipecac/huana

A

mechanism: local irritation (similar to hydrogen peroxide); direct central activation of the receptors in the CTZ

Pharmacokinetics: oral admin, but we don’t really know the action of how it works. onset of action is relatively short

Uses: emetic

Side effects: uncommon but OD can lead to cardiotoxicity

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14
Q

Xylazine

A

mechanism: alpha 2 adrenoceptor agonist (sedative also)

direct central activation of receptors in CTZ–> in most species, CTZ has alpha 2 adrenoceptors

IV or IM admin

emetic in cats because they have a high number of alpha2’s in CTZ

sedative, analgesic

Side effects: sedation, CV side effects

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15
Q

Apomorphine

A

mechanism: dopamine agonist (doesn’t activate opioid receptors)
- receptors in CTZ

Oral absorption is slow, parenteral admin (IV/IM) preferred.

drug of choice for emesis in dogs

Side effects: protracted vomiting; excitement, restlessness; CNS effects due to stimulation of dopamine receptors in CNS.

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16
Q

Treatment of vomiting- antiemetics

A

Dopamine antagonists (antidopaminergics)

histamine antagonists (antihistamines)

muscarinic antagonists (anticholinergic)

Neurokinin antagonists

Serotonin antagonists

17
Q

Phenothiazines

A

primarily sedatives- i.e. acepormazine is a phenothiazine

Mechanism: block dopamine receptors in CTZ; weak anticholinergic and antihistamine

Oral admin- can give IM too

well absorbed and distributed- significant 1st pass metabolism

excreted by kidneys

Broad spectrum antiemetic

side effects: hypotension, bracycardia d/t anticholinergic action; sedation

18
Q

Metoclopramide

A

Mechanism: dopamine antagonist- also some antimuscarinic effects

Prokinetic reaction: stimulate peristalsis through muscarinic action; increase smooth muscle sensitivity through ACh

Oral, SC, IM or slow IV admin

50% first pass metabolism

excreted by kidneys

Uses: antiemetic, treatment for oesphagitis, gastric motility disorders

Side effects: movement disorders, fatigue

19
Q

Diphenhydramine

A

mechanism: antihistamine, antimuscarinic

particularly effective for motion pathway

Oral admin

uses: antiemetic for motion sickness

side effects: mild sedation d/t antihistamine effects

20
Q

Neurokinin antagonists

A

e. g. maropitant (cerenia)
mechanism: NK-1 receptor antagonist–> shuts down emetic pathway

NK is final gate-keeper in emetic pathway

Oral, SC admin

Hepatic metabolism: high reliane on this- contraindicated with hepatic dysfunction

uses: broad spectrum antiemetic

side effects: hypersalivation, diarrhea

Relatively good safety profile due to specific nature

21
Q

Serotonin antagonists

A

e.g. odansetron

Mechanism: blockade of serotonin receptors in CTZ

uses: if metaclopramide is ineffective- not widely used, very expensive. used to treat vomiting associated with cancer chemo

22
Q

Treatment of diarrhea

A

diagnose/treat primary cause

dietary modification: acute vs. chronic diarrhea

Anti-diarrheal agents: adsorbents, opioids, anticholinergic, aminosalicylates

23
Q

Adsorbents

A

e.g. kaolin (Al3+ salt) suspension

Mechanism: absorb toxins; provide protective coating on inflamed mucosa

Uses: symptomatic therpay of acute diarrhea- primary thing it does is change consistency of the feces

24
Q

Opioids

A

e.g. codeine, diphenoxylate, loperamide (immodium)

diphenoxylate and loperamide don’t cross BBB when taken orally–> no CNS effects that we’d normally expect with opoids.

Mechanism: inhibits ACh release in myenteric plexus–> slows gut down; gives chance to reabsorb water

Uses: symptomatic therapy of acute diarrhea

Given PRN

Can exacerbate absorption of microbial toxins from decreased gut activity/slower transit

Constipation is major side effect of opioids (analgesics)

25
Q

Anticholinergics

A

e.g. hyoscine (buscopan), atropine

Mechanism: muscarinic antagonist

Uses: antispasmodic–> symptomatic relief of pain (such as in IBD or colic)

Can help to improve rectal compliance

26
Q

Aminosalicylates

A

e.g. sulfasalazine, osalazine

Mechanism: cleaved by bacteria in bowel to sulfapyridine and 5-aminosalicylic acid (related to aspirin)

salicylates have an anti-inflammatory effect–> inhibit PG synthesis?

Minimal absorption: dose reaches colon; minimal absorption in rest of GIT, very few side effects

Useful in chronic IBD/colitis

27
Q

Laxative/cathartics

A

Lubricate, add bulk, osmotic, stimulant

28
Q

Lubricant

A

mineral oil, liquid paraffin

lubricate tract and soften feces

limited absorption

minor words of caution: lubrication of GIT can interefe with absorption of certain things in GIT like fat-soluble vitamins over a long period of time.

29
Q

Bulk

A

adding dietary fiber to absorb H2O

e.g. methylcellulose, agar, wheat bran

Hydrophilic colloids absorb water and increase bulk

stimulates peristalsis

slow to take effect- something for animal prone to constipation- build-in as regular feature of diet

30
Q

Osmotic

A

e.g. magnesium sulphate, polyethylene glycol, lactulose

non-absorbale salts/polymers

retain water in intestinal lumen- decrease consistenct, soften stools

cathartic of choice for elimination of poisons

31
Q

Stimulant

A

e. g. bisacodyl, phenophthalein
v. effective- can be so potent that you get excess fluid loss

stimulate intestinal motility via an irritant effect- promote organized peristalic action

avoid in severe constipation.