19 – Gastrointestinal Therapeutics

Question 1

What are two issues with appetite?

Answer 1

• Obesity
• Animals not wanting to eat due to illness (especially cats)
• *Interspecies differences: genetic where they do not feel satiety

Question 2

Physiology of appetite control: basic

Answer 2

• Complex
• Satiety center in hypothalamus
• Multiple hormones involved
• NTs: serotonin and peptide YY stimulates ‘satiety’

Question 3

What is Dirlotapide (Slentrol)? Not in Canada, still in USA

Answer 3

• Oral solution for overweight dogs
• Fat sits in enterocytes for longer=feel satiety via peptide YY
  o ‘decreases’ food intake (not increase metabolism or less fat absorption)
• *don’t use in cats (hepatic lipidosis) or people
• Not sure why discontinued in Canada

Question 4

What is Orlistat (Xenical)? Human product

Answer 4

• Pancreatic lipase inhibitor
• Extremely low oral bioavailability
  o Okay since works in GI lumen
• Decrease dietary fat digestion/absorption
• *DIARRHEA

Question 5

How to get cats to eat more food?

Answer 5

• Wet food
• Fish in it=aromatic
• Warm it up=may smell better

Question 6

What is Mirtazapine? (human generics)

Answer 6

• Human anti-depressant
  o Serotonin and NE

Question 7

Mirtazapine: mechanism of action

Answer 7

• Stimulates release of NE
• Increases specific serotonergic (5-HT1) receptor activity
• Potent antagonist of 5-HT2 receptors
  o *Likely cause INCREASE of appetite
• Potent antagonist of 5-HT3 receptor
  o Likely cause anti-nausea/anti-emetic effects
• Potent antagonist of histamine (H1) receptors
  o Can cause sedation

Question 8

What drug can be used for cats to increase appetite?

Answer 8

• Mirataz 2% gel rubbed on inside of cats ear (Transdermal)
• Once daily for 1-2 weeks
• 2mg/cat (4 cm strip)
• *if works=polyphagia within 36 hours

Question 9

What is the pharmacokinetics of Mirtazapine?

Answer 9

• Hepatic and renal excretion
  o Need to adjust dose or interval with hepatic or renal disease?
• Half life: 9-16h (VARIABLE)
• May start to accumulate over time (giving every 24hrs but still some drug left)

Question 10

Low vs. high oral dose of Mirtazapine in cats

Answer 10

• Higher dose=longer the half life
• *both doses ate similar amounts of food
• Higher: vocalized and interacted more
• *use LOWEST dose if want to get them to eat
• TRANSDERMAL IS JUST AS GOOD=EASIER

Question 11

Glucocorticoids as an ‘appetite stimulant’

Answer 11

• Polyphagia is the side effect
  o More in dogs than cats
  o Only a transient effect (days to weeks)
  o Often used in palliative cases (ex. oncology)

Question 12

What is the mechanism of glucocorticoids increasing food intakes?

Answer 12

• Inherent activity OR
• Secondary to general ‘perking up’?
• *silly to use it to increase appetite alone

Question 13

Anabolic steroids

Answer 13

• Testosterone analogs
  o Suppress fat slightly
  o Stimulate muscle production!
• Have been used in horses
• *CONTROLLED DRUGS: most are off the market

Question 14

Benzodiazepines as an ‘appetite stimulant’

Answer 14

• Diazepam, Oxazepam
• Cats: INDIVIDUAL effect
  o If it works, it works
  o But doesn’t work on others
• *giving it more, does NOT make it better (make it sleep more)

Question 15

Cyproheptadine as an ‘appetite stimulant’

Answer 15

• Some cats will get polyphagia
• INDIVIDUAL: hit or miss

Question 16

Capromorelin as an ‘appetite stimulant’ (USA only)

Answer 16

• Works at level of brain
• Increase food intake and weight gain (NOT dramatic, better than nothing)
• Elura: cats (for chronic kidney disease!)
• Entyce: dogs (general appetite stimulant)
• Adverse effect: vomit/diarrhea (odd)

Question 17

Omeprazole and Maropitant as an ‘appetite stimulant’

Answer 17

• DID NOT work