pharmacology Flashcards
What are glucocorticoids used for?
-respiratory disease-asthma
-dermatological disease- atopy/food allergy
-gastrointestinal disease-IBD
-ophthalmic disease-anterior uveitis
-musculoskeletal disease-immune-mediated myositis
-neurological disease- meningitis
-Immune-mediated and autoimmune disease
Species differences for prednisone
Cats and horses have low bioavailability of prednisone-low capacity to convert prednisone to prednisolone
Species differences-cats v dogs
-cats require higher doses
-cats have fewer glucocorticoid receptors
-cats have lower affinity glucocorticoid receptors
-cats are more resistant to adverse effects
Glucocorticoid effects
-increase the number of neutrophils and monocytes
-decreased lymphocytes, eosinophils, and basophils
-decrease function (release of inflammatory cytokines)
Glucocorticoid adverse effects
-immunosuppression at higher doses (TREATS OVERACTIVE IMMUNE RESPONSE)
-chronic low doses have effects on innate and cell-mediated immunity
-hyperglycemia
-increase triglycerides, cholesterol, glycerol
-muscle breakdown
-stabilize membranes and decrease vascular permeability
-stimulate ALP production in dogs
-hepatomegaly
-GI ulceration
-alterations in fluid and electrolyte balance
-polyuria/polydipsia
-accidents in the house within 5 days
-mood and behavior changes (polyphagia)
-laminitis (horses) (can’t be replicated in experiments)(fat horses with cresty necks (EMS) are predisposed)
How to prevent adverse effects of glucocorticoids?
-give drugs every other day
-taper dose when d/c treatment (not necessary with short term treatment)
-give dose in the morning to prevent alteration in sleep
-localize therapy (results in less systemic exposure)
What are the prostanoids you need to know and their effects?
-PGI2=anti-platelet; vasodilatory
-TXA2=pro-platelet; vasoconstriction
-PGE2=pro-inflammatory, pain; vasodilation; GI motility; fever
-PGF2alpha=vasoconstriction; SmM contraction (uterus, GIT); luteolysis
What do COX-2 inhibitors do?
-Block the bad (pro-inflammatory effects)
-Leave the good (cytoprotective to the GIT)
-no adverse effects
What are the clinical uses of NSAIDs?
-to treat endotoxemia
-anticoagulant
What are NSAIDs not appropriate for?
-Immune-mediated diseases (IMHA/IMTP)
-Autoimmune diseases
-Allergic diseases
-Inflammatory respiratory diseases (asthma, chronic bronchitis)
-Neurologic disease (meningitis)—-doesn’t cross BBB
Adverse effects of NSAIDs
-GI ulcers (stomach and SI in cat and dog) (stomach and right dorsal colon in horses)(abomasum in ruminants)
-PGE2 effects (necessary for healing with pre-existing damage)
-nephrotoxicity (inhibition of PGE2 and PGI2 causes vasoconstriction, decreased renal BF (blood flow), possible toxicity)
-Lesions in the kidneys (characterized by medullary crest or papillary necrosis)
-COX-1 inhibitor=inhibits platelet function
-hepatotoxicity (mainly in dogs)
-blood dyscrasias (phenylbutazone in dogs)
-Injection site reactions (heat, pain, swelling, abscess formation, tissue necrosis, clostridial myositis)
-PHENYLBUTAZONE=severe tissue necrosis when given peri-vascular
-IM FLUNIXIN MEGLUMINE= clostridial myositis (huge abscess)
How to minimize adverse effects of NSAIDs?
-Prevent injection site reactions by given drug another route (oral)
-dose appropriately (lowest effective dose at the longest effective dosing interval)
-choose COX-2 selective
-dedicated dosing syringe
-GI protection
-Avoid co-administration of other nephrotoxic drugs
-use EXTREME caution in animals with underlying disease
-client education
-monitor
What is MIC?
-Minimum Inhibitory Concentration=the lowest concentration of drug that inhibits visible bacterial growth
What is MBC?
-Minimal Bactericidal Concentration=the lowest concentration of a drug that kills 99.9% of bacteria
What is a bacteriostatic drug?
-A drug that stops the bacteria from multiplying but doesn’t kill the bacteria
-relies on the host immune system to kill bacteria
-not ideal for immunosuppressed patients
What is a bactericidal drug?
-A drug that kills bacteria directly
-preferred for immunosuppressed patients or severely ill patients
What is PAE?
-Post antibiotic effect
-occurs once MBC and MIC decline in plasma
-bacteria still around and evade host immunity
-persistent sites of infection
What are the antibiotic mechanisms of action?
-Inhibit cell wall synthesis
-inhibit cell wall function
-inhibit nucleic acid synthesis and function
-inhibits protein synthesis
What type of bacteria is penicillins effective against?
-active against streptococci NOT most staphylococci
-Not active against gm(-)
-active against some gm(-) and gm(+) anaerobes
What type of bacteria is amino-glycosides effective against?
-active against staphylococci NOT most streptococci
-active against respiratory and enteric gm(-)
-no activity against anaerobes
What type of bacteria are macrolides effective against?
-active against gm(+) anaerobes
-active against respiratory gm(-) but not enteric
-active against most gm(+) anaerobes
What are the routes of administration of antibiotics for systemic infection?
-IV=severe illness, fast effect
-IM=severe illness, when IV is not possible
-SubQ=avoid in dehydration
-Oral=bioavailability lower, variable absorption; avoid in GI diseases; drug interactions
What are the routes of administration of antibiotics for local infections?
-topical=eyes, skin, wounds
-inhaled=pneumonia
-intraarticular/regional limb perfusion=synovial infections
-transdermal=NEVER
What are the type of beta lactam antibiotics?
-penicillins
-cephalosporins
-carbapenems=imipenem and meropenem
-monobactams=aztreonam
How do beta lactams work?
-they penetrate the outer cell wall of the bacteria
-bind to and inhibit penicillin binding proteins (PBPs)=transpeptidase enzymes required for cross-linking of cell wall precursors
-inhibition of cross-linking=opens channels through cell wall to creates holes that allow fluid into the cell causing cell swelling and death
What kind of antibiotics are beta lactams?
Bactericidal
Do beta lactams distribute well intracellularly or extracellularly?
-distribute well in extracellular fluid
-minimal intracellular activity
-do NOT distribute to protected sites
Beta lactams effects on metabolism
-minimal, with the exception of ceftiofur
How are beta lactams eliminated?
-glomerular filtration and tubular secretion
-HIGH HIGH HIGH concentrations in urine
-1000x higher concentration in urine than in plasma
General pharmokinetics of beta lactams?
-short half life that requires frequent dosing with the exceptions (cefovecin, cefriofur crystalline free acid)
Benzylpenicillins (penicillin G)
-still effective against streptococcus (gm+) species and anaerobes
-inactivated by beta lactamases
-toss up if it will treat staphylococcus
Penicillin G
-oral absorption limited bc it degrades in gastric acid
-IV formulations=expensive bc it’s a human drug
-IM/SC formulations have longer half lives=less frequent doses
-cheap
Aminopenicillins
-includes ampicillin and amoxicillin
-good oral absorption in small animals (amoxicillin is better than ampicillin “o”=oral)
-limited to no oral absorption in large animals
-increased spectrum against gram (-) bacteria—–in lower urinary tract
