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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Ghrelin

A
  • Located in peripheral tissues, release by empty stomach

- Oppose leptin action in hypothalamus, increase food intake/decrease energy expenditure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Mirtazapine

A
  • Piperazino-azepine antidepressant
  • 5HT-1 agonist - inhibits serotonin reuptake
  • Sympathetic (norepi) actions reflect antagonism of a2 auto-receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cyproheptadine

A
  • Antihistamine with antiserotonin properties

- MOA - inhibition of serotonergic receptors that control appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Propofol

A

-Anecdotally stimulate appetite through GABA-A and NYP stimulation, serotonin inhibition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Phenothiazines (chlorpromazine, mepazine, prochlorperazine, triflupromazine, etc.)

A
  • Broad spectrum antiemetics effective for central causes except labyrinthine stimulation
  • Block emesis at CTZ at low doses due to antidopaminergic (D2) and antihistaminergic effects. Some weak antiserotinergic effects too.
  • Primary adverse effects are sedation and hypotension (alpha blockade)
17
Q

Butyrophenone derivatives

A
  • Haloperidol & droperidol
  • Potent antiemetics due to anti-dopaminergic activity.
  • Rarely used due to side effects (similar to phenos but more profound)
18
Q

Metoclopromide

A
  • Blocks emesis at CTZ - D2 antagonist, 20 times as potent as phenos
  • Mixed 5HT3 antagonist/5HT4 agonist - anti-emesis at high doses due to 5HT3
  • Peripheral anti-emetic effects d/t prokinetic
19
Q

Serotonin antagonists

A
  • Ondansetron potent antiserotonergic (5HT3) effects, no effects at other receptors
  • Active metabolite (dolasetron)
  • Cyproheptadine (anti-H2 and anti-5HT3) used for vomiting and diarrhea
20
Q

Miscellaneous antiemetics

A
  • Sedatives (barbituates & benzos) can control pyschogenic/behavioral vomiting
  • Glucocorticoids (dexamethasone esp) have unknown antiemetic effects
  • Cannaboids inhibit vomiting, likely via CB1 receptor stimulation
21
Q

Peripheral antiemetics

A
  • GI protectants: protect epithelium from irritation and prevent vomiting - demulcents, antacids, kaolin/pectin/bismuth salts
  • Anticholinergics: block muscarinic receptors in emetic center & inhibit peripheral cholinergic transmission (glyco only peripheral - no BBB). Inhibition of vagal afferents, relaxtion of GI smooth muscle spasm; delayed gastric emptying - do not use >3d; do not use with drugs that depend on cholinergic activity (opioids, cisapride, metoclopromide)
  • Prokinetics: (reglan) - inc esophageal sphincter tone, duodenal pyloric relaxation, antegrade antrum contraction
22
Q

H-2 receptor antagonists

A
  • Reversible, competitive inhibitors that reduce H ion content of gastric secretions and amount of pepsin
  • Famotidine (9x)> Ranitidine (5-12x) > Cimetidine
  • Oral Bioavailability opposite (cemitidne 70%, ranitidne 50%, famotidine 37%)
  • Impair oral absorption of some drugs; dec hepatic metabolism of other drugs (CYP - cimetidine>ranitidine>famotidine); famotidine preferred d/t inc potency, fewer drug interactions
  • Potential for rebound gastric acid hypersecretion
23
Q

Proton Pump Inhibitors (PPI - omeprazole/pantoprazole)

A
  • Most potent anti-secretory drugs, reducing gastric acid secretion 80-95%
  • Potent, irreversible antagonist of H+K+/ATPase proton pump (prodrug, protonated to be transformed into active inhibitor)
  • Lag time of 3-5 days before maximal effect
  • Partial inhibition of drugs eliminated by selected cytochrome P450 enzymes have been reported for omeprazole
  • The potential for inhibition of drug metabolism because of drugs or disease may result in longer drug half-lives of other drugs
  • Diarrhea and transient fluctuations in liver enzymes have been reported
  • Rebound hypersecretion of gastric acid as described for antihistaminergic drugs should be anticipated, and discontinuation of proton pump inhibitors should occur gradually
  • Only famotidine, pantoprazole, and omeprazole suppressed gastric acid secretion, compared with placebo.
24
Q

Prostaglandin analgoues

A
  • Misoprostol is a methyl ester analog of prostaglandin E1
  • actions appear to be mediated by interaction with a basolateral membrane receptor. Intracellular concentrations of cAMP decrease, which in turn decreases protein kinase activity and hydrogen ion concentration
  • Oral, onset 30 mins, half life 20-40 mins
  • Basal, nocturnal, and food-induced gastric acid secretion is inhibited
  • Can cause diarrhea, can induce uterine contractions and is contraindicated in pregnancy
  • primary indication for misoprostol is prevention or treatment of NSAID-induced ulceration
25
Q

Sucralfate

A

-disaccharide (octasulfate of sucrose) aluminum hydroxide product that binds to and protects damaged epithelial cells from acid, bile, and pepsin activity
-sucrose is freed from aluminum hydroxide, cross-polymerizes, and binds to exposed (damaged) anions of GI epithelial cell membranes
-administered at least 30 minutes before antacids and on an empty stomach, 1 hour before feeding (needs acidic env <4 to work)
-binds to and inactivates bile acids, thus promoting its use in biliary disorders, and inhibits pepsin-mediated hydrolysis of mucosal proteins.
last up to 6 hours
-Sucralfate appears to stimulate production of local mediators that protect the gastric mucosa. These include prostaglandins sulfhydryl ions or other oxygen radical scavengers, and epidermal growth factor
-Sucralfate also increases mucosal blood flow either by inducing local nitric oxide or prostaglandin production or by directly stimulating mucosal angiogenesis
-Sucralfate binds to a number of drugs, with the prototypic example being cimetidine
-minimally absorbed after oral administration and is associated with few, if any, side effects.
-does not prevent the formation of the ulcer; rather, protects damaged tissue once it occurs

26
Q

Bethanecol

A
  • Ester derivative of choline, acts as cholinergic agonist at M2 receptors
  • Enhance amplitude of contractions throughout GIU including LES
  • Coordination of SI contraction minimal - not considered prokinetic
  • Side effects: enhanced parasympathomimetic stimulation - cramps, diarrhea, salivation, bradycardia
27
Q

Metoclopromide (prokinetic)

A
  • Lipid soluble derivative of para-aminobenzoic acid; structurally related to procainamide
  • Central anti-dopaminergic effects (antiemetic)
  • Peripherally anti-dopaminergic & indirect stimulation of cholinergic receptors: enhanced release of ACh from intrinsic cholinergic neurons (inhibited by pretreatment with anticholinergic)
  • Prokinetic activity: muscarinic activity, D2 receptor antagonist, 5HT4 agonist activity.
  • Effects limited to LES (tightens), stomach (antegrade contraction in fundus), and pylorus (relaxation) - but also says promotes peristalsis in SI (???)
  • Oral bioavailibility 50-70% (1st pass effect)
  • Dose dependent CNS effects: nervousness, restlessness, depression, disorientation; tremors, motor restlessnes.
  • Opioids and atropine antagonize action
28
Q

Domperidone

A
  • Dopamine antagonist, prokinetic properties similar to metoclopromide but not cholinergic activity, not inhibited by atropine
  • Dose not cross BBB easily - can have some central antidopaminergic effects
29
Q

Cisapride

A
  • Broadest spectrum of all prokinetics: dose-dependent activity increase from esophagus (less so in cat) through colon
  • Appear to be mediated by indirect stimulation of cholinergic nerves, mediated by serotonin through 5HT4 receptors
  • Colonic contraction via 5HT2a
  • Stimulation probably occurs at myenteric plexus (GI secretion not enhanced)
  • Prolonged elimination in hepatic disease
  • No central dopamine receptor activity, no extrapyramidal effects
  • Stimulation of 5HT4 by cisapride (or others) can cause blockade of rapid K+ influx through delayed rectifier potassium channel: QT prolongation -> torsades de pointes -> +/- fatal arrhythmia (no cardiac side effects reported in veterinary species) - increased risk with other drugs that inhibit CYP450
30
Q

Erythromycin

A
  • Stimulates GI motility as sub-antimicrobial doses
  • Effects mimic motilin: enhances LES pressure, incoordinated stomach contraction
  • Rapid tolerance d/t downregulation of motilin receptors
  • Other macrolides have similar effects to variable degrees (may explain GI side effects in dogs on for antibiotic use)
31
Q

H2 (ranitidine) - prokinetic

A

-Inhibit anticholinesterase activity - prokinetic at antisecretory doses