Unit 2 - Pharmacokinetics Flashcards
WHat is the def of pharmacokinetics
movement of drugs into, through and out of the body
What is pharmacodynamics def
involves how drugs interact with tissues to exert physiological changes
What are the 4 components of pharmacokinetics?
Absorption - how drug get into plasma; routes of admin;bioavailability
Distribution - movement of drug in plasma to the “target tissue” and other tissue
metabolism - biotransformation. 1st pass effect
elimination - how drug gets out of the body; renal elimination; enterohepatic recycling
What 4 mechanisms exist by which drugs can cross lipid membranes?
passive diffusion, facilitated diffusion, active transport, pinocytosis and phagocytosis
How does passive diffusion work?
Most common and important
random movement
from high->low conc across a semi=permeable membrane
unlimited
drug must be lipid soluble, non ionic and small
How does facilitated diffusion work?
lger molecular weight drugs
very similar to passive diffusion except that diffusion occurs across pores/channels loc in the lipid bilayer
some selectivity bc specific pores may only let certain types of molecules thru
still req high-low conc gradient
How does active transport work
active movement of a drig molecule across a lipid membrane via a pump or transporter
use of energy allows movement from low to high conc; allows high drug accumulation in tissues
transporter/pump will only bind to specific drugs
ex. P-glycoprotein pump
What is phagocytosis and pinocytosis and how does it work?
active swallowing or drinking of drug molecules by the cell
may be thru “Random sampling” of molecules in the extracellular environment OR may result from drugs binding to receptors on the cell surface
What are factors that affect the rate of drug molecule movement?
drug form, smaller sized frugs diffuse more readily across membranes
carrier molecule ability, for those drug dependant on a carrier - How quickly does it reset, how many carriers available, speed of transport, saturation limit
conc gradient diff, temp
thickness of membrane
lipophilic nature of the drug molecule
How does being lipophilic or hydrophilic affect drug molecule movement
lipophilic - dissolves readily in fat but do not readily dissolve in water - to move across a membrane, drug molecules must be lipophilic
Hydrophilic - dissolves readily in water but do not dissolve readil in fat
What is absorption?
Describes movement of drug from site of administration until it enters the plasma (what happens during the absorption period
What is absorption determined by?
chemical nature of the drug
how it is formulated
route of admin
patient
What does absorption influence in regards to bioavailability
Influences how much of the initial dose ends up in the plasma (this is measured as bioavailability)
What is bioavailability
A mesure of drug absorption
% of drug administered into the body that enters the systemic circulation
What is an example of 100%, 50% and 0% bioavailability
100% bioavailable - all drug entered plasma
50% bio - half original dose entered plasma
0% bio - none of drug entered plasma despite being given to the patient
What bioavailability does IV drugs have?
100% bioavailabilty
Fastest onset of action greatest bioavail, #1 choice for emerg drug deliver
Beware of inc risk of entering toxic range w/ rapid bolus admin
What bioavailability does IM drugs have?
close to 100% bioavailability
active muscle has inc blood flow compared to inactive muscle
What bioavailability does PO have
quite variable, may be affected by first pass effect
What does formulation include in regards to drugs and formulations?
formulation includeds anything added to the pharmaceutically active ingredient - syrups, other liquids, flavors, color, gel coats for tablets, creams and ointments, alcohols
Formulation determines which routes of admin can be used - drugs formulated for oral dosing cannot be given IM, etc
What are generic equivalents
generic equivalents have the same active drug molecule. they do not necessarily have the same formulation
formulation affects absorption and drug stability
Therefore, generic equivalents may have diff absorptions and diff bioavailability
formulation is specific to a DIN (import when comparing equivalents: not all generic equivalents act the same)
What are the effects of lipphilic or hydrophilic nature of a drug on absorption
whether a drug exists in a hydro or lipophilic form when admin’d, will affect ability for drug molecule to dissole or pass thru cellular membrane
drug has to be the proper ionization for the route of admin
A drug in hydro form more rapidly absorbed via IM or SQ
Lipo form more absorbed PO
What is the rule about drug pH and enviro pH effect on absorption
Drugs act as either weak acids or weak bases
“Like is non-ionized in like”
A drug that is a weak acid, will be non-ionized in an acid enviro. Bc non-ionized will be more lipid soluble
Same drug in a basic enviro will be ionizes (less lipid soluble)
non ionized = HCL vs ionized H+ Cl-
Give an example of pH and drug ionization with aspirin
Aspirin is a weak acid, given by PO and enters stomach (acidic)
Apply the rule that drug is in the same enviro then its non-ionized. Then asparin is weak acid, in stomach acid, is non-ionized
Non ionized molecules are lipophilic; therefore aspirin more likely to cross cellular membranes in stomach
Asparin absorbed from stomach
What are an ionophores? Are they weak acids or weak bases
A type of drug that prevent coccidiosis in the rumen. In order for the drug to work, must stay in rumen which is very acidic. Weak acids
What is ion trapping?
movement of drug into a compartment where it changes from a hydrophobic state to a hydrophilic state, and stays in that compartment
Ex. Asparin lipophilic, move across stomach wall-blood vessel walls-circulation. Once in plasma, has less similar enviro, becomes ionized and more hydrophilic. Aspirin trapped in plasma
What is P-clycoprotein and MDR 1 gene mutation?
P-glycoprotein is encoded by the MDR1 gene
it is an active transport pump found in cells of the intestinal epithelium and BBB
a genetic mutation of the MDR1 gene can lead to a lack of functional P-glycoprotein which leads to inc susceptibility to drug toxicosis
drug lvls build up in CNS as pumps not pumping it out
What breeds are affected by MDR1 deficiency? What happens if its hetero or homozygous
many herding dogs like collies, shelties, border collie, australian sheperds and very young kittne
Hetero mutation prods some functional pumps; less affected
homo is more severely affected
pump can also be inhib by certain drugs
What is cytochrome P450 (CYP enzymes)
Enzyme located in cells of intestinal wall
metabolizes same drugs that P-glycoprotein removes from cell
need to keep in mind if drugs or dz or other drugs inhib the func of these enzymes a correct dose will deliver a larger than expected quantity of drug
alternatively, some drugs with long term use may induce these enzymes therefore dose may need to inc over time ex phenobarbital
Why does PO have the lowest bioavailability?
- degradation in saliva, stomach acid, sm int, GI flora(PO not common in ruminants bc of lg # of microbes in rumen will degrade most meds b4 can be absorbed)
if peristalsis too fast, drug passed w/o chance to absorb - note that GI transit times in dogs/cats faster than humans, faster transit if diarrhea, oral drugs more if constipation
First pass effect
What are some patient factors affecting absorption?
yg anims may have poor oral absorption
vomit and diarrhea dec oral absorption
constipation inc oral absorption
fever/heating sources in rate of absorption for IM, ID, SQ, transdermal routes
Cold causes vasoconstriction and dec ID, SQ absorption
BCS - fat poor perfusion; dec SQ absorption
Ruminants - PO absorption typically poor
What pH is ideal for acid drug and base drug of ionized or non-ionized form
Acid drug in enviro of pH 9
Acid pH 2
Base pH 2
Base pH 9
How does drug distribution work?
describes the movement of drug from the plasma into the tissues
a drug is only effective if it makes it to the target tissue
There is a constant movement of drug btw plasma and the diff tissues
What are drug factors affecting distrubition
- chemical nature of the drug; especially its solubility in aqueous solution vs fat-solubility
- degree to which the drug binds to albumin and other plasma proteins
- “volume of distribution” a pharmacological measure of how much of a drug leaves or stays in the plasma
Why do size and ionization matter?
sm molecules have inc ability to cross semi-permeable membranes by passive diffusion
lg molecules cannot pass thru fenestrations of blood capillaries
non-ionized (lipophilic) molecules will diffuse acoss lipid membranes. Ionized (hydrophilic) molecules will not
How does plasma protein binding work?
many drugs bind to plasma proteins, such as albumin and globulin, as soon as they reach the circulation
protein bound drugs are not active - too big to leave circulation; only unbound drugs are active and can leave the circulation into tissues
plasma protein binding is a dynamic equilibrium - constantly binding and detaching
In regards to plasma protein binding in drugs, what do dosages need to take into acount
what will happen if a patient is hypoproteinemia? how low lvls of plasma proteins
causes of hypoproteinemia include: starvation, protein losing enteropathies/nephropathies, liver failure
In regards to protein bound drugs, what happens with concurrent drug use?
if two highly protein bound drugs are given at the same time but one has more affinity for protein binding, it make preferentially bind to protein leaving more of the other drug free to be active, therefore see increased effects from the other drug
What is the volume of distribution?
property of the drug determined in testing phase
measure of how much drug leaves the circulation and enters the extracellular fluid
Drugs with High Vd, leave the plasma more readily and enter the tissues
drugs with a low Vd have a harder time leaving the circulation
used to determine drug dosage
What patient factors affect drug distribution?
blood flow
% body water - degree of hydration, affects the total conc of dissolved drug plasma, other extracellular fluids and intra cellular fluids
Dehydrated and older anims have lower %BW and may req lower dosages of drugs to achieve a given plasma conc
Tissue barriers and membrane permeability - some tissues easier for drugs to get into than others
