Boothe GI Flashcards
1
Q
Leptin
A
- Produced by white adipose tissue
- Inhibits food intake, increases energy expenditure and increases insulin sensitivity (AMP kinase)
- Influences thermogensis, increase hematopoiesis, angiogenesis, wound repair
- Glucocorticoids stimulate leptin expression
- Leptin may inhibit insulin secretion, peripherally competes with it; other reports - no effect
2
Q
Acetylation-stimulating protein (ASP)
A
- Produced from complement factor C
- Increased glucose uptake and diacylglycerol acyltransferase activity, decreased hormone-sensitive lipase
- Concentrations increase with increased lipids, in proportion to body fat in obese humans; decrease in states of fasting
- Adipocyte triglyceride synthesis and storage increase after eating, inc FFA and TriG clearance
- Reduces hepatic glucose production
3
Q
Adiponectin
A
- Secreted by adipocytes, necessary for normal insulin activity
- Decrease circulating glucose independent of fat content, & without affecting insulin - decreased hepatic glucose formation, increased tissue use by decreasing insulin resistance
- Concentration negatively correlated wiht body fat (esp visceral fat) content
- Dec by catecholamines, cytokines, glucorticoids - insulin resistance
4
Q
Ghrelin
A
- Located in peripheral tissues, release by empty stomach
- Oppose leptin action in hypothalamus, increase food intake/decrease energy expenditure
5
Q
Mirtazapine
A
- Piperazino-azepine antidepressant
- 5HT-1 agonist - inhibits serotonin reuptake
- Sympathetic (norepi) actions reflect antagonism of a2 auto-receptors
6
Q
Benzodiazepines (diazepam, oxazepam)
A
- Induce appetite through gabaminergic effects and central inhibition of satiety center in hypothalamus
- Do not stimulate appetite as well in dogs as in cats
- Hepatotoxicity (appears idiosyncratic) with use of diazepam for app stimulation in cats
7
Q
Cyproheptadine
A
- Antihistamine with antiserotonin properties
- MOA - inhibition of serotonergic receptors that control appetite
8
Q
Megestrol Acetate
A
- Synthetic derivative of progesterone
- Targets cachexia via direct and indirect stimulation of appetite and antagonizing catabolic effects of cytokines
- Increased basal insulin conc, inc response to carb load, inc lipoprotein lipase, modulation body temp
- Inhibits formation TNF-a, IL-1, IL-6; modulate central neuroT that regulate appetite (NPY)
9
Q
Dirlotapide
A
- Selective microsomal triglyceride transfer protein inhibitor - blocks assembly and release of lipoprotein into bloodstream
- Weight control mechanism unclear - decreases GI fat absorption, increased lipid filling of enterocytes (satiety signal)
- Orally bioavailable in dog but nonlinear kinetics (hepatic metabolism)
- May affect absorption of fat soluble vitamins (A & E); possible ophthalmic side effects
10
Q
Propofol
A
-Anecdotally stimulate appetite through GABA-A and NYP stimulation, serotonin inhibition
11
Q
Emesis
A
- Different afferent pathways all coordinated by emetic center (lateral reticular formation) coordinates afferent peripheral and central neural signals (substance P - tachykinin neuropeptid)
- Emetic center close to CTZ (adjacent to area postrema bottom of lateral ventrcile - not protected by BBB)
- CTZ coordinates vomiting associated with blood-borne chemicals
- Psychogenic vomiting (cerebral cortex), head trauma/inc ICP (limbic system)
- Solitarius nucleus - receptors for enkephalin, histamine(H1), 5HT-3, ACh - ACh major afferent at higher centers, H1 secondary transmitter
- Substance P (tachykinin neuropeptide) - key neurotransmitted associated with emetic center, targets NK1 (neurokinin) receptors throughout emetic center
- CTZ stimualted by bloodborne compounds - mediated by D2, 5HT-3, H1, NK1 receptors; numerous opioid receptors in CTZ
- Vestibular apparatus -> CN VIII -> vestibular nuclei - CTZ via H1 receptors
- Peripheral impulses from pharynx via CN IX to emetic center; also via visceral organ irritatation/stretch (sympathetic or vagal afferents) from heart, stomach, SI, liver, GB, kidney, UB, uterus, etc. - primarily mediated by ACh (muscarinic receptors to emetic center via CN X)
12
Q
Peripheral emetics
A
- Distention of pharynx/esophagus/GI with warm water or saline
- Irritation of GI or pharynx with warm NaCl solution, NaCl directly in pharynx
- Oral H2O2 (3%) rapid emesis in dogs and cats (potential fatal aspiration)
- Ipecac - alkaloid emetine - increases lacrimation, salivation, bronchial secretions +/- vomit (peripheral & central); may kill cats, not recommended
13
Q
Central Emetics
A
- Drugs (esp opiates) that stimulate CTZ
- Apomorphine - only marginal depressant activity, stimulates D2 receptors more than other opioid actions; stimulates vomiting in CTZ but depressed emetic center - subsequent doses won’t work if 1st doesn’t
- Xylazine (cats) - A2 stimulation at lower doses than sedation
14
Q
Maropitant Citrate
A
- NK1 receptor antagonist - blocks substance P in area postrema and nucleus solitarius
- High 1st pass metabolism, better availability SQ than oral
- Bone marrow hypoplasia in puppies less than 11 weeks
- Specificity for NK1 makes safe and effective (better than chlorpromazine, metoclopromide; not better than ondansetron) for central and peripheral causes of emesis
15
Q
Vestibular emesis
A
- Vomiting caused my vestibular apparatus can be controlled by antihistamines (cyzlizine, meclizine)
- Can cross BBB and may directly effect emetic center in addition to histaminic effects
