3017 - gastrointestinal drugs 1

what is vomiting

Forceful / active expulsion of gastric and intestinal contents from mouth

What does serotonin (5-HT3) do in vomiting?

It strongly triggers vomiting, mainly by activating the CTZ and gut nerves.

Where is serotonin released from?

From gut (enteric) neurons and the brain.

What else does serotonin control?

Mood, wakefulness, feeding, and vomiting.

What drug blocks serotonin to stop vomiting?

Ondansetron

What is Substance P?

A chemical that causes nausea and vomiting by binding NK-1 receptors.

What drug blocks NK-1 receptors?

Maropitant

Why is maropitant so effective?

Because Substance P is a major vomiting trigger

What does dopamine do in vomiting?

It makes the CTZ more sensitive and helps coordinate the vomiting action (salivation, stomach movement, abdominal contractions).

What drug blocks dopamine to reduce vomiting?

Metoclopramide

What else does dopamine normally do?

Motivation, movement, arousal.

What does acetylcholine (ACh) do in vomiting?

Controls the muscle movements of vomiting and gut movement (peristalsis).

Where does ACh act?

On muscarinic receptors in the GI tract and vomiting muscles.

What does metoclopramide do to acetylcholine?

It increases acetylcholine release in the gut → helps stomach empty.

What does glutamate do in vomiting?

It makes the vomiting centre more sensitive to other signals (serotonin, dopamine, Substance P).

What receptor does glutamate use?

NMDA receptors

Why is glutamate important?

It amplifies vomiting signals.

Are glutamate blockers used clinically yet?

Being researched, especially for chemotherapy nausea.

What do NORADRENALINE & ADRENALINE affect

• Vestibular system (motion sickness)

• CTZ

• Gut movement

what do NORADRENALINE & ADRENALINE do to the gut

Reduce gastric motility → stomach stasis

What does histamine do in vomiting?

Activates the vestibular system (motion sickness) and a bit of the CTZ.

What histamine receptors are involved?

H1 receptors → vomiting
H2 receptors → stomach acid

What drugs block histamine?

• H1 blockers = Antihistamines (for motion sickness)

• H2 blockers = Famotidine (for acid, not vomiting)

What does “emesis” mean?

Induced vomiting to remove toxins from the stomach.

What does the success of emesis depend on?

• Agent used

• Time since ingestion

• Gastric motility

• Stomach contents (food affects absorption)

Why does food in the stomach matter during emesis?

It can delay absorption or change how much toxin is absorbed.

When is emesis most effective?

When performed soon after ingestion and before the toxin leaves the stomach.

What species is apomorphine mainly used in?

dogs

How does apomorphine cause vomiting?

It is a dopamine agonist that stimulates the CTZ.

What forms does apomorphine come in?

• IV

• Conjunctival tablet

• Transmucosal

What must you do if apomorphine is given in the eye?

Rinse the conjunctiva after vomiting occurs

What side effect can apomorphine cause?

CNS depression

is apomorphine reversible

yes

Why is apomorphine less useful in cats?

Cats often get CNS stimulation instead of vomiting

What species are xylazine and dexmedetomidine used for emesis in?

cats

How do XYLAZINE & DEXMEDETOMIDINE cause vomiting?

They are α2-adrenergic agonists

What major side effect do they cause?

CNS depression

What household substances have been used to induce vomiting?

• Soda crystals

• Hydrogen peroxide

• Dishwashing liquid

• Syrup of ipecac

Why is table salt contraindicated for emesis?

Risk of acute hypernatraemia (dangerous sodium levels)

When might at-home emetics be considered?

• Owner cannot reach a vet

• Life-threatening poisoning

• Very recent ingestion

Which drug class commonly causes vomiting as a side effect?

Opioids (e.g., morphine, hydromorphone)

What is often given after inducing vomiting?

An antiemetic to stop further vomiting

Why give an antiemetic after emesis?

To prevent continued vomiting, aspiration, and dehydration

What are antiemetics?

Drugs that prevent or stop vomiting.

What are the 4 main antiemetics you need to know?

• Maropitant

• Metoclopramide

• Ondansetron

• Prochlorperazine

What is maropitant’s mechanism of action?

Neurokinin-1 (NK-1) receptor antagonist → blocks Substance P.

Why is maropitant such a powerful antiemetic?

Because Substance P is a major final pathway for vomiting.

What is maropitant used for?

• Vomiting from many causes

• Before chemotherapy

• Motion sickness (higher dose)

What formulations does maropitant come in?

• Injectable (slow IV, SQ)

• Oral

What are the main cautions with maropitant?

• Liver disease (hepatic metabolism)

• < 8 weeks old → bone marrow hypoplasia

• > 5 consecutive days use

What practical tip reduces pain on injection?

Refrigerate before giving SQ (stings less)

Does motion sickness need higher or lower doses?

Higher doses than for nausea

What is metoclopramide’s antiemetic mechanism?

Dopamine (D2) receptor antagonist in the CTZ

Besides antiemetic effects, what else does metoclopramide do?

It is prokinetic → increases GI motility

Why must you be careful using metoclopramide with GI foreign bodies?

Increased motility could worsen obstruction or cause perforation

Is metoclopramide more effective in dogs or cats?

more effective in dogs

What formulations does metoclopramide come in?

• Injectable: IV, IM, SQ, CRI

• Oral

What is the standard metoclopramide CRI dose?

2 mg/kg/day

For a 10 kg dog, how much metoclopramide CRI per day is needed?

2 mg/kg × 10 kg = 20 mg total

What is ondansetron’s mechanism of action?

Serotonin (5-HT3) receptor antagonist

Where does ondansetron work?

• Centrally in the CTZ

• Peripherally on vagal nerve terminals in the GIT

What is ondansetron used for?

• Vomiting from many causes

• Before chemotherapy

What is a major advantage of ondansetron?

Very wide safety margin

What formulations does ondansetron come in?

• IV injection

• Oral wafers or tablets

What class of drug is prochlorperazine?

Phenothiazine

Where does it act?

CTZ and vomiting centre

What receptors does prochlorperazine block

• Dopamine

• Histamine (H1)

• α2-adrenergic

• Muscarinic

Why is prochlorperazine considered a “broad” antiemetic?

Because it blocks many vomiting pathways

What are the main side effects of prochlorperazine?

• Vasodilation

• Drowsiness / sedation

What are prokinetics?

Drugs that increase gastrointestinal (GI) motility.

What are the 3 main prokinetic drugs you need to know?

• Cisapride

• Metoclopramide

• Erythromycin

What parts of the GIT can prokinetics affect?

• Oesophagus

• Stomach

• Small intestine

• Colon

What is cisapride’s mechanism of action?

stimulates GIT smooth muscle → increases motility.

What does cisapride increase?

• Lower oesophageal sphincter pressure

• Gastric emptying

• Small intestinal motility

• Colonic motility

What is cisapride used for

• Gastric stasis

• Oesophageal reflux

• Chronic constipation / megacolon (especially cats)

How is cisapride supplied?

Compounded as:

• Capsules

• Liquid

• Transdermal cream/gel

Why was cisapride removed from the human market?

It can cause prolonged QT interval → dangerous heart arrhythmias

How does metoclopramide work as a prokinetic?

It sensitises upper GIT smooth muscle to acetylcholine.

What effect does METOCLOPRAMIDE have in the stomach?

Increases antral (stomach) contractions → better gastric emptying

What effect does metoclopramide have on the oesophagus?

Increases lower oesophageal sphincter tone (thought to reduce reflux).

Which part of the GIT does metoclopramide mainly affect?

Upper GIT (oesophagus + stomach)

What is erythromycin normally used for?

As an antibiotic

How is erythromycin used as a prokinetic?

At sub-antimicrobial (low) doses to stimulate motility.

What receptors does erythromycin act on?

• Motilin receptors in cats

• Serotonin (5-HT3) receptors in dogs

What does erythromycin increase?

• Gastroduodenal emptying

• Lower oesophageal sphincter pressure

• Small and large bowel peristalsis

What formulations does erythromycin come in?

• Injectable (IM, IV)

• Oral

Which drug class decreases intestinal motility?

opioids

What effect do opioids have on the gut?

Decrease intestinal contractions → constipation

Why should opioids NOT be used for diarrhoea?

• They have systemic side effects

• If diarrhoea is infectious, slowing gut movement can increase toxin absorption

What are gastroprotectants?

Drugs that protect the stomach lining and/or reduce gastric acid.

What are the 4 main classes of gastroprotectants?

• Proton pump inhibitors (PPIs)

• H2 receptor blockers

• Sucralfate

• Prostaglandin analogues (misoprostol)

How do protein pump inhibitors (PPIs) work?

They block the final step of acid secretion by inhibiting the H⁺/K⁺ ATPase proton pump

Why are PPIs so effective?

They block acid production at its final common pathway.

What PPIs should you know?

• Esomeprazole (Nexium) – IV, PO

• Pantoprazole (Somac) – IV, PO

• Omeprazole (Losec) – PO

When might PPIs be given before surgery?

18–24 hours before to reduce gastric acidity.

How should oral PPIs be given?

• On an empty stomach

• 1 hour before food

Why should PPI tablets not be crushed or broken?

They need the enteric coating to survive the acidic stomach.

Why should other anti-secretory drugs not be used with PPIs?

They can delay the onset of PPI action.

How do H2 blockers work?

They block histamine (H2) receptors on parietal cells → less acid secretion.

What H2 blockers should you know?

• Ranitidine

• Famotidine