Quiz I Flashcards
What are collies sensitive to and why?
Ivermectin, due to mutant deletion of ABCB1 gene which encodes for the P-glycoprotein, and important part of the BBB
What drug do Australian terrier no respond to (no sedation) but instead have salivation, tachycardia, muscle tremors and convulsions?
Droperidol/fentanyl
Young animals have _____ total body water and _____ developed metabolic systems
higher, less
Liver dz ____metabolic function
reduces
Renal dz generally _____ renal clearance
reduces
A dog in congestive heart failure will have better or worse drug distribution and clearance?
worse/reduced
Is idiosyncratic drug rx dose dependent and can it occur on first exposure?
NOT dose dependent
can occur on 1st exposure
The most common hypersensitivity type associated with drug immune response is ____. Drugs commonly act as ______.
Type I
Haptens
What is a decrease in responsiveness to the same administered dose of drug over time?
tolerance
What is acute tolerance called?
Tachyphylaxis
Why does pharmacodynamic tolerance occur?
Changes in receptor (down regulation, change in receptor sensitivity)
Why does Pharmacokinetic tolerance occur?
Changes in absorption, metabolism or excretion
What is cumulation?
elimination slower than absorption
Summation
two drugs have additive effects
Synergism
Two drugs have greater efficacy when combined
Chemical Antagonism
drugs react to each other inactivating one or the other
Physiologic antagonism
drugs cancel each other out
Pharmacokinetic antagonims
One drug reduces the concentration of another, interferes with its ADME processes
Acidifying urine increases excretion of ______
weak bases
Alkalinizing urine increases excretion of ______
weak acids
What are boxers sensitive to?
Phenothiazines (acepromazine)
Facilitated diffusion
carrier mediated, may be selective, moves with conc gradient passive
Active Transport
Carrier mediated
Saturable
Selective
Moves against conc gradient, requires energy
Primary active transport
ATP supplied directly
Secondary Active Transport
Indirect, after ATP is used to create a electrochemical gradient
Pinocytosis
Endocytosis, drugs bind to surface of cell, cell membrane and envaginates. Requires energy.
What is the 1st part of absorption and the rate limiting step?
Dissolution
Bioavailability
fraction of given does that ends up in systemic circulation
Is topical use intended to be absorbed systemically?
No
Where does most absorption take place?
Small intestine
What is Enterohepatic recycling?
When a drug is absorbed from portal circulation then excreted in bile and reabsorbed in the small intestine again.
What is 1st pass metabolism?
an oral drug is absorbed into portal circulation and a portion of the drug is metabolized by the liver before is reaches systemic circulation.
Parenteral
IV, IM, IP, SQ injections
What 3 ways can you manipulate a drug for better transdermal absoption?
lipohilicity (lipid vehicle)
local humidity (like a fentanyl patch)
very high local conc
Are lipophilic drugs more like to get into the CNS? How?
Through fusion of cell membranes
Acidic drugs typically bind to ______
albumin
Basic drugs bind to _____
B-globulins and glycoproteins, sometimes to alb
Metabolism/Biotransformation definition
chemical alteration of drug by different body tissues
Bioinactivation
process of making the drug inactive and easier to excrete
Prodrug, Bioactivation
Prodrug- inactive substance
Bioactivation- inactive to active metabolite
Lethal synthesis
nontoxic substance converted into a toxic metabolite
Phase I Metabolism
oxidative hydrolytic rxns
Takes place in hepatocytes with cytochrome P450 enzymes aka mixed function oxidase system
Phase II Metabolism
a molecule w/ a reactive group conjugates with a substiuent group rendering a final metabolite that is inactive and water soluble (polar)
Gulcuronidation is the most common rxn and is microsomal
Conjugatin can be reversable (enterohepatic) recycling
What species is deficient in glucuronyl transferase?
cats
What species are deficient in acetylation?
dogs and cats
What species are deficient in sulfation
pigs
What species only uses ornithine due to lack of oxidative enzymes?
birds
Phenobarbital and phenylbutazone are enzyme ______
inducers
A decrease in the capacity of metabolic enzymes is called
enzyme inhibition
Glomerular filtration
passive, depends on molecular size and protein binding
Active tubular secretion
drugs move against a conce gradient using transporters
OCTs move ______
OATs move ______
OCTs= organic bases OATs= organic acids
Tubular reabsorbtion
passive diffusion, lipid soluble and nonionized drugs can move back into circulation along their conc gradient
You have a weak basic drug and a urine with a pH of 4. What will happen regarding ionization and excreation
the drug will be ionized and excretion will be enhanced
Alkanization of urine with Na bicarb or K citrate will cause weak acids to be ______
ionized and enhance their secretion
Renal excretion is ______ in neonates
lower
Hepatic excretion
active transport/conjugates from hepatic sinudoids to bile caniculi. Lipid soluble drugs with MW >300 and a polar group more easily excreted
What are other methods of excretion besides kidney and hepatic?
fecal, milk, and eggs
