pharm (davis) Flashcards
What 3 receptors and antiporter lie on the basal side of a gastric parietal cell?
basal side = blood vessel side
Histamine, gastrin, AcH; HCO3+/Cl- antiporter
Cl goes in, bicarb goes out
What pump lies on the luminal side of a gastric parietal cell?
H+/K+ ATPase pump (in most animals, is inactive inside the parietal cell)
K+ goes in, H+ goes out (into stomach)
How is HCl- formed in stomach?
H+ and Cl- leaving the gastric parietal cell on luminal side
(H+ gets pumped out via H+/K+ ATPase pump; Cl- diffuses passively out of the cell)
Suppression of gastric acid production
H2 receptor antagonists
Histamine receptor
Ranitidine, famotidine
- reversible, competitive inhibitors
- reduce amt. of gastric acid present in gastric secretions -> increase gastric pH
- less efficacious w/ chronic dosing; rare ADEs
Famotidine does not have cancer-causing agent that’s found in ranitidine
Suppression of gastric acid production
Proton pump inhibitors
H+/K+ ATPase pump
Omeprazole, Pantoprazole
- irreversibly inhibit -> no H+ to combine with Cl- to form gastric adic –> decrease gastric acid // increase gastric pH by 95%
- Omeprazole: given in an inactive form –> ionized and activated intracellularly (therefore, [plasma] do not relate to effect
have replaced most of H2-receptor antagonists, but can be used adjunctively b/c PPIs take a couple days for full effect
Suppression of gastric acid production
Mucosal protectants
Sucralfate (complex of sucrose & AlOH)
- Works at bicarb border inside of stomach to help heal gastric ulcers (AlOH binds to damaged GI epithelial cell membranes)
- binds to/inactivates bile acids
- stimulates PGEs –> increased mucosal blood flow (which aids with ulcer repair), negative feedback on acid production
- adjunctive tx only - not strong enough for monotherapy
- give 2 hours apart from other drugs!!
gastroduodenal ulvers, esophageal ulcers, colon ulcers
Suppression of gastric acid production
Prostaglandin analogue
synthetic prostaglandin E1 (PGE1)
Misoprostol
- Suppresses gastric secretion & improves mucosal bloow flow
- Use for NSAID-induced ulcers, and equine glandular ulcers
- Abortifacient!!! Owner education & safety!!
- has been shown to decrease pruritus by 30% in atopic dermatitis dogs (anti-inflamm. effects)
negative feedback (activate PGE receptor -> suppression)
Suppression of gastric acid production
Antacids
- Work in lumen to break apart HCl- bonds
- require q2h dosings (large volumes, frequently)
- contain AlOH (chelate other drugs like fluroquinolones)
Which H2-receptor antagonist is most potent?
Famotidine (> ramitidine = nizaditine > cimetidine)
What is the only FDA-approved drug in vetmed for treating gastric ulcers?
Omeprazole; only in horses (all other uses = off-label use)
Ulcergard; Gastrogard — both exact same thing, only difference = dosage
Omeprazole vs Pantoprazole regarding clinical uses
twice daily dosing is likely needed for dogs/cats
Why must omeprazole be administered in a buffered form?
To reach and be absorbed in the SI
Hay diets in horses & omeprazole
Omeprazole should be administered on an empty stomach//30 mins before a meal (all species).
All-hay diets blunt effects of omeprazole (during tx) but are recommended in horses with hx ulcers (prevention– want hay in the stomach as a buffer)
Why does omperazole absorption increase with dosing?
B/c there is less acid available to break down the omeprazole
less acid b/c omperazole is breaking that down
Describe proper dosing scheduling of ABX (tetracyclines, fluoroquinolones) with sucralfate
Give abx, wait 2h, then give sucralfate
Not following this regimen can cause decrease in therapeutic concentrations of the antibiotic and therefore increase risk of microbial resistance devleoping!!!
Why are antibiotics never a first-line tx for gastric ulcerations in veterinary species?
Helicobacter spp. not significantly found to be associated with gastric ulceration in veterinary species
only found in gastric ulcers of foals and non-healing ulcers in horses
What receptors do drugs that induce emesis work at?
D2, NK1, 5-HT
Which species do not/rarely vomit?
Horses cannot vomit; cows/swine rarely do
Ropinirole
Clevor
- dopamine agonists (affinity for D2) in CRTZ in brain
- rapid absorption across conjunctival mucosa, highly metabolized and rapidly eliminated via urine
Apomorphine
- derivative of morphine (NOT an opioid)
- D2 agonist
When should you use Ropinirole over Apomorphine 100% of cases?
MDR1-mutation dogs
- apomorphine causes more severe v+ (# & duration) and more severe CNS depression
- Ropinirole is NOT a substrate for p-glycoprotein
MDR-1 mutation: these dogs are homozygous for the mutation, where they LACK P-GLYCOPROTEIN EFFLUX PUMPS @ BBB
What drug class is used to induce v+ in cats
Alpha-2 agonists (cats have more alpha-2 receptors in CRTZ. dogs have more dopamine receptors).
Thiazine-derivative anti-emetics
- Acepromazine
-
Chlorpromazine - PO drug
- acts on emetic center, CRTZ and peripheral receptors
- not used often anymore
- long-term sedation, but can have idiosyncratic effect of hyperness/somewhat aggressiveness
Prokinetic Agent: Metoclopramide Mechanism and effects
Central dopaminergic antagonist (@ CRTZ), also works at peripheral serotonin receptors => CNS & GI effects
- CNS effects: b/c it crosses the BBB (CRTZ signals to the emetic center, which is within BBB), it can cause extrapyramidal signs (Parkinsons-like = uncontrollable muscle tremors/spasms)
- GI effects: stimulates parasymp. activity, stimulates/coordinates esoph, gastric, pylorc and duodenal motor activity
Clinical uses of metoclopramide
- mainly in dogs (sometimes for cats) for anti-emetic effects
- particularly useful in dz with decreased GI motility (parvo; megaE)
- post-operative ileus in horses
Erythromycin used more frequently for abomasal emptying in cattle compared to Metoclopramide
Why is metoclopramide always given as a CRI in horses?
Slower admin @ lower concentrations b/c the drug causes intense CNS effects (crazy+++ and aggressiveness)
also never give in conjunction w/ chlorpromazine
Maropitant citrate
Cerenia
- inhibits binding of substance P to NK-1 receptors (substance P stimulates emesis –is an emetogen) in CRTZ, emetic zone, peripheral vagal receptors in GIT
- PO and inj (dogs) – PO: small amt of non-fatty foods (fatty foods delay dissolution)
- Inj only (cats)
pre-op maropitant may lower anesthetic requirements and provide additional analgesia for GI and reproductive procedures
100% of patients administered cerenia 45 mins before opiod admin for surgery experienced NO pre-op v+
PO has higher does than SC b/c PO has greater first-pass metabolism
Ondansetron
Peripheral & Central action:
- Peripheral = reduces vagal n. activity
- Central = 5-HT3 antagonist at CRTZ
- short half life
- ADE: prolonged QT intervals
Mirtazapine
- Alpha-2 antagonist
- serotonin and histamine receptor antagonist
- renal/liver disease cats: drug when given PO has prolonged clearance/half life -> Adjust dose!
- no increase in ADE when administered at label doses transdermally
ADE: vocalization, restlessness, agitation, tremors/trembling, vomiting, hypersalivation, tachypnea, tachycardia, lethargy, ataxia, abnormal gait
Capromorelin
Entyce (dogs); Elura (cats)
- mimics “hunger hormone” = ghrelin (makes your stomach go Ghrrrrrr…elin)
bitter taste; use in hospital
What 2 GI drug/drug classes chelate other classes like fluoroquinolones and tetracylines?
Mucosal protectant (sucralfate) & Anatacids
Contain AlOH
