pharamacology exam 2 Flashcards
respiratory anti-inflammatory drugs glucocorticoids
-used for equine RAO, feline asthma and canine bronchitis:
* High dose, chronic oral glucocorticoids.
-steroids blunt inflammatory response.
-use lowest dose which will lead to effect. will lead to systemic effects after long term use.
Beneficial effects of glucocorticoids on airway:
- ↓ severity of airway inflammatory symptoms
- ↓ airway response to ongoing allergens
- possibly prevent airway wall remodeling?
NET EFFECT: ↑ effective airway radius = ↑ airflow - ↓ recruitment of airway eosinophils (↓ leukotrienes)
systemic glucocorticoids different species
- Prednisone: dogs at 1 mg/kg PO EOD (not good for cats/horses) they use prednisolone.
-methylpredisolone: watch for diabetes in cats
-Dexamethasone powder or injection for horses
Inhalent (aerosolized) Glucocorticoids
Less systemic absorption, ↓ HPA suppression
* Fluticasone (Flovent®, generics)
* Most potent, longest acting
* Ciclesonide (Aservo EquiHaler): causes coughing and nasal discharge.
best way to manage inflammatory airway disease
- Bronchodilators (b-2 agonists) = treatment of inflammatory airway disease signs
- Steroid = prevention of airway inflammation
-use these two together. use bronchodialator first to max absorption.
-must manage allergen from environment.
mirtazapine mechanism of action
-Stimulates release of norepi
- Increases specific serotonergic (5-HT1) receptor activity?
* Potent antagonist of 5-HT2 receptor
* Likely cause of ↑ appetite
* Potent antagonist of histamine (H1) receptors
* Can result in sedation
Mirtazapine doses
-increase appetite-polyphagia
-Mirataz 2% – transdermal gel placed on inner pinna of cat’s ear
Oral = generic human tablets (15 – 45 mg)
-dose =2mg/cat
-good in acute settings
-should work at 36 hr.
-causes vocalization and interaction behavior (less for transdermal)
drug induced polyphagia as a side effect
-glucocoirticoids:* Typically observed more in dogs than cats
* Usually only a transient effect (days – weeks)
-anabolic steroids: (test) use in chronic illness with weight loss. controlled drugs now due to abuse.
opioids for diarrhea and vommiting
- Anti-secretory and anti-motility effects by acting on μ (and other?) receptors in GI tract = constipation
- Loperamide (Imodium®, OTC) stays in gut causes constipation in healthy.
-Don’t use with infectious diarrhea or in known ABC-B1 deletion dogs
Antimicrobial Therapy for diarrhea
-only for known bacterial causes.
-antimicrobials can cause diarrhea by changes to natural flora in gut. (nuflor, Baytril)
-only use when animals with bad inflamed diarrhea it breaks down mucosa and bacteria can get into blood. (ex neonatal calves without colostrum, parvo puppy) to manage secondary septicemia.
-beware OTC calf scours boluses, they don’t work.
NSAIDS for diarrhea (not very useful)
-Meloxicam has label claim for calf diarrhea (w/ oral fluid therapy)
-ketoprofen, flunixin (when blood in feces)
-increase appetite due to feeling better?
gastric mucous protection
-mucus layer coating cells
-tight junctions for no HCL passage
-mucosal cell membrane not permeable to HCL.
-Bicarb in mucos
-rapid cell turnover
-pepsinogen inactive from when secreted.
-need BF to stomach wall to make mucous ect.
how acid is produced in stomach
-when pH goes up gastrin stimulates partial cells and proton pump produces acid. and Ach from eating. and histamine on H2 receptors.
-neg feedback loop when pH gets too low somatostatin comes in stops production.
proton pump inhibitors for ulcers mechanism
-blocks acid production
-due to uncer there are less protective mechasnisms in that area
-blocks adenylate cyclase enzyme which stops acid production.
-stops proton pump of K for H ion.
Omeprazole (Gastrogard®
-proton pump inhibitor
* Short T1/2, but long effect (irreversible inhibition)
* 4 mg/kg: for ulcer tx
* 1 mg/kg: prevent ulcers
Watch out for:
* GI ulcer relapse when off therapy
* Chronic gastric acid reduction leads to hypergastrinemia ( Mucosal cell hyperplasia, rugal hypertrophy, & carcinoids)
* CYP-enzyme inhibitor (watch for drug interactions)
-PPI in dogs and cats should be tapered after prolonged use > 3-4 weeks
emetics
-Commonly used after toxin ingestion
-apomorphine
-a-2 agonists (emetic for cat IM) xylazine and dexmedetomadine. (50%)
-hydrogen peroxide
-saturated salt solution
Apomorphine:
-Emetic (causes vommiting)
-dopamine agonist in CRTZ
◦ ~ 90% effective as emetic for dogs, less effective emetic in cats
◦ Administered in conjunctiva (eye) or IV
◦ Other opioids may induce vomiting too
◦ E.g., hydromorphone (anesthesia pre-med)
Phenothiazine drugs (sedatives):
Acepromazine (Atravet®) – injectable and powder only
-anti-emetic
-Antagonizes dopamine:
* Inhibits the CTZ &/or emetic center
* Can decrease vomiting from other causes (e.g. motion sickness)
-antihistamine in dogs, weak anticholenergic cats.
-ADR: hypotension/ sedation, extrapyramidal signs (aggressive), seizures.
-good short form like car ride.
Antihistamines (H1 blockers) as an anti emetic
- Block both cholinergic (cats) and histaminic (dogs)
nerve transmission responsible for transmission of
vestibular stimuli to the emetic center - Mild sedation, especially diphenhydramine
(Benedryl), dimenhydrinate (Gravol)
Metoclopramide (injectable solution)
-anti emetic
* Low doses: inhibits dopamine in the CNS
* Peripheral prokinetic effect: increases gastric and
upper duodenal emptying
* High doses: inhibits serotonin receptors in the CRTZ
* Extrapyramidal effects (like acepromazine
-not used much now, older vets maybe.
-Ondansetron (Zofran® & generics
-serotonin antagonsit
-very $$$
* Inhibit 5-HT3 (serotonin) receptors on vagal nerve & CRTZ
-great for chemotherapy vommiting!! not motion sickness or sickness.
- Cytotoxic drugs and radiation release serotonin
Maropitant (Cerenia®, Emavert)
-big anti emetic drug in small animal
A neurokinin (NK1) receptor antagonist:
* Blocks binding of substance P (tachykinin) at emetic center
-blocks drug induce vommiting (apomorphone)
-labeled for acute vommiting (2mg/kg) and motion sickness
-maybe good as analgesic and anti-inflammatory
Maropitant (Cerenia®) formula and adverse effects
Formulations:
◦ Oral tablets (labelled for dogs only)
◦ Injectable formulation (dogs + cats)
Adverse effects:
◦ Can cause bone marrow hypoplasia in young puppies
◦ So be careful with parvo dogs < 16 weeks
◦ Contraindication: suspected GI obstruction
Use in cats: effective for many causes of vomiting
◦ Dose at 1 mg/kg to start
◦ Long term use in cats
Anti-emetics for Parvo-induced emesis
- “Metoclopramide, ondansetron and maropitant used as anti-emetic
drugs in the treatment of Parvoviral enteritis reduced the severity of
vomiting starting with the first day of treatment, and reduced the
number of vomiting starting with day 3 of treatment”
treatment of diarrhea (non drug)
Fluid therapy:
◦ Diarrhea doesn’t kill animal, dehydration & acidosis do
Electrolytes:
◦ Replace sodium, chloride, probably potassium
Acid/base treatment:
◦ Bicarbonate to treat acidosis
◦ Metabolizable substrates that produce bicarb
◦ citrate, propionate, acetate
how oral rehydration therapy works
-Fluids must contain – H2O, Na and a cotransporter (AA or glucose)
-Na has many ways to enter mucosa cell. water follows Na ions into the cell. you need glucose or amino acid as cotransporters to bring in water by osmosis.
Anticholinergic Drugs for diarrhea
- Significantly ↓ intestinal motility and secretions. only good for hypermotile diarrhea. (not many cases)
-side effect tachycardia and decreased gut sounds.
-Hyoscine butylbromide (Buscopan) used in collics to supress intestinal spasm in horses.
-some people use it for diarrhea but not effective.
Potassium Bromide (KBr)
- VERY old anti-epileptic drug (1857 in humans!)
- Likely hyperpolarizes neural cell membranes
-adverse effects in dogs: sedation, vommiting, diarrhea. polyuria and phagia. plevic limb weakness/ stiffness.(with bromide toxicity) not ataxia. pancreatitis, skin lesions.
-not recommended in cats! coughing and bronchial asthma.
Potassium Bromide Kbr pharmacokinetics
- Extremely long half life (24 d)
– Can use “loading” dose for first week - 120 – 160 mg/kg (4x the maintenance dose)
– Once at steady state: missing single dose not critical - Elimination: Renal (but reabsorbed with Cl-)
– No hepatic metabolism (so ↓ drug interactions)
Potassium Bromide Kbr food interactions/ overdose treatment
-no drug but has food interactions
-salt diet: decreases br reabsorption from renal tubule increases excretion so less br in blood.
-cardiac diets (low salt): increase Kbr in blood and reabsorption.
* Treatment of overdose
– IV 0.9% NaCl, 10 mL/kg/h for 12 hours
Diazepam (Valium®) treatment
-treat status epilepticus in cats and dogs Not generally used for seizure prevention.
-IV crosses BBB rapidly.
-rectal bioavaliability is 50% so give 2x dose. or intransal 80%
-dont use oral, low bio.
* Hepatic metabolism: two active metabolites:nordiazepam & oxazepam.
Diazepam: Adverse effects
- Lethargy, sedation, ataxia
– But as anticonvulsant: probably due to seizure, not diazepam - Hyperactivity?
- Increased appetite (weight gain)
- Seizures may occur if abruptly stopping chronic diazepam
- Reports of fulminant hepatic necrosis in cats
– Idiosyncratic (not dose-dependent) reaction.
-use for prevention in cats not chronic!
newer anticonsolvent problems
Most efficacy studies with new(er) anticonvulsants:
* Typically administered as add-ons
* Non-controlled (no placebo)
* Typically small sample size
* Often not blinded
* Imprecise outcome measures (owner scores)
ex: Levetiracetam (Keppra®, gabapentin, cannabindoil.
Levetiracetam (Keppra®)
-added to PB or Kbr as added therapy. works good, not as great as sole therapy.
-Used for cluster seizures
– 20 mg/kg PO, TID
* Previous: Start at 10 mg/kg BID and work up
– High oral bioavailability
– Short T1/2 (3 – 4h)
– Renal excretion:
* Good choice if worried about hepatic disease
-tolerance after 4-8 months.
-fatal AE in dog after rapid iv injection
Brivaracetam
-anti consolvent
* Newer, more potent analogue of levetiracetam
* Single dose PK study performed in cats:
– Good oral bioavailability
– Plasma concentrations in therapeutic range for humans
– Longer T1/2 elim than levetiraceteam (maybe allows BID dosing?)
– Adverse effects mild (sedation, ptylalism)
Gabapentin as an anticonsolvent
– Structural analogue of GABA, but doesn’t appear to impact
GABA receptors!
* Block or modulate Ca
– May be given in combination with PB &/or KBr in dogs
– Frequent administration in dogs: 10 mg/kg TID
-sedation/ ataxia
Pregabalin (Bonqat®)
– Oral solution now approved as anxiolytic in cats before car transport
* NOT approved as anticonvulsant
-50% reduction in sieziers
-sedation/ ataxia
H2 receptor antagonists
-Block parietal cell HCl secretion through H2 receptor inhibition
-* Cimetidine (Tagamet®)
* Ranitidine (Zantac®)
Famotidine (Pepsid® AC)
-not much efficacy in dogs/ cats use PPI
-Orally absorbed, but low F in horses & ruminants
-Lipid soluble (Vd > 1 L/kg)
-Short T1/2 elim
-CYP inhibition: ↓ metabolism of other drugs: Cimetidine is notorious!
