4 L =
V/T x C
dose (mg) / [in bld]
loading dose =
Vd x [desired in serum]
(Vd x k)/ T1/2
extraction ratio =
Ca-Cv / Ca
rate of elmination /[ drug in plasma]
rate of elmination =
urine flow x [drug in urine]
the sutdy of drugs on biological system
application of pharmacological prinicpals to clinical patients
any substance which can affect a biological system
therapeutic factors taht affect the administration of a drug:
onset of action
site of action
drug factors that affect the administration of a drug;
adv: safe, economical, noninfectious
dis adv: inactivation, palatability, slow onset
adv: can give large volumes, accurate, and fast onet
adv: slow absoprtion but constant, long duration of acitivyt
disadv: slow onset
adv: rapid onset, duration of action is longer than IV
disadv: can cause tissue damage
the study of doses
the amount of drug given to an animal to have an effect
the amount of drug per unit body weight
types of doses:
therapeutic, lethal, toxic
minimal therapeutic dose
the small amoutn that has a therapeutic effect
maximal therapeutic dose
the largest amount that can be tolerated without producing toxic effects
the optimal dose, which lies between the maximal and minimal doses. has a desirabel effect
Mediam effective dose. affects 50% of the animals
meidal lethal dose. kills 50% of the animals
the amount that produces undesirable clinical, hematological, biochemical or pathological alterations
relative safety of drugs is calculated by:
standard safety margin
the higher the TI the safer the drug
Standard safety margin
ssfactor = Ld1/Ed99
ld1-ed99/ed99 x 100 is a percent that is more accurate then TI
anesthetics can be harmful to...
small mammals and breeds with short respiratory tracts
cows lack ______ on certain organs?
dont use ______ on rabbits
an enzyme tha tis used for conjugation. NOT IN CATS!!! will help to metablize salicylate (asprin).
the half life of asprin in cats will _______ due to little of what enzyme?
increase, glucuronyl transferase
opiods in cats will cause miosis? T or F
FALSE!! causes mydriasis
asprin use in dogs....
will cause an inflammatory reaction due to the convertion of arachadonic acid to leukotrienes instead of PGs
single nucletotid polymorphisms. in less than 1% of the population. no necessarily in a gene,and do not alwyas affect protein functions
"indicative SNP" are not within the gene. do not affect protein funciton.
affect hte way a protein fucntions. there si coding and noncoding
coding causative SNP
located in the codon region to change the amino acid sequence
noncoding causative SNP
located in the gene regulatory sequence changes the level of gene expression.
what do the young and the old have in common?
-decrease ability to biotransform
-decrease drug excretion
-decrease protein binding
NSAID effect on a nomral patient
will decrease COX-2 = decrease inflammation
decrease COX1 = decrease vasodilation = decrease bld flow to kidney
NSAID effect on hypotenion patient
total lack of blood flow to the kidney. can lead to renal failure
genetically determined unpredictable abnormal reaction to drugs.
fever, uticaria, anaphylaxis
resistance to ordinary dose of a drug. decrease responsivness to repeated doses of same or similar drug
tolerace to a drug type other than the one that induced tolerance
acute tolerance to repeated administration of a drug.
time scale = hours
the rate of elminiation is slower then the rate of absorption
occurs following concurrent or sequential administration of drugs.
can be summative, synergistic, additive, or antagonistic.
can be beneficial or toxic
enhace the excretion of weak acid drugs by ion trapping
enhances the excretion of weak base drugs by ion trapping
factors related to the enviornment
stress, diet, temp, humidity, oxygen
transfer of a drug from the site of injection to circulation
factors that affect absorption related ot the drug:
degree of ionization
dissolution in water
concentration at the site
route of administration
how does molecular size affect absorption?
small = fast absorption, aqueous diffusion or thoruhg a lipid channel
large = absorption is lower via facilitated diffusion or endocytosis
how does lipid solubility affect absorption?
increase lipid content = increase diffusion
increase water solubility= decrease diffusion`
how does ionization affect absorption?
nonionized drugs are more important for passive diffusion
increase NI/I ratio and increase diffusion
how does dissoluiton in water affect absorption?
-oral absorption of a liquid is faster than a solid
how does concentration at a site affect absorption?
- high concentration will increase absorption rate.
how does route of administration affect absorption rate?
oral is slower than injection
factors that affect absorption related to the drug
-absoring surface area
how does blood flow affect absorption?
increase blood flow = increase absorption
bld flow can be modified by heat, massage, other drugs, sympathetic NS, and edema
hear tnad kindey disease will.......(bld flow)
increased edema therefore decreased blood flow
shock will ___ blood flow
decrease blood flow therefore decrease absorption.
how does the absorbing surface area affect absoritong?
increase surface area = increase absorption
upper part of the SI is the best area for this
will determine the rate of absorption in the SI
what about an individual can impact absorption?
food presense in the GIT
diarrhea will___ absorption
first pass effect
drug biotransforamtion that will reduce the quantity of drug that reaches circulation.
-per os administration
-occurs due to gastric enzymes
movment of drugs from blood to tissues
what affects distribution ofa drug?
make up of the drug
the formation of a substance is equal to its removal.
affected by area, permability, membranes, bld flow and concentration
tissues that are highly perfused
brain, heart, kidney, liver, endocrine glands
bound drugs are inactive and are unable to be filtere, metabolized, or distributed.
-reversible, pro-longs half-life
-keeps the drug high in the plasma low in the tissue.
mostly bind to albumin
what affect does liver failure have on protein binding?!
protein bidning will be decreasebecause the liver amkes the palsma proteins
tissue binding consequences:
may increase the concentration of a drug in a tissue
drug is pulled outof the plasma
the tissue will hold onto the drug which will increase the time the drug is in the body
Nonionized drugs exert a diffusion pressure? T or F
weak acids are trapped in...
acid compartments trap______.
the study of the movment of drugs across biological memrbanes form the time of absorption until elmination
movment from high concentration to low concentration. dependent on lipid solubility
oil : water ratio
increase the ratio = increase passive diffusion
lipophilic and hydrophilic =
O2 and N2
small uncharged polar molecules
urea and water
can passively diffuse
large uncharged polar molecuels
glucose and sucrose
will not diffuse
will not pas the lipid barrier
T or F? It is possible to look at the pK and determine if a drug is a weak acid or base?
strong acid + weak base =
(Hcl, H2SO4, PO4)
strong base + weak acid =
(NaOH, Ca2OH, KOH)
specific type of endocytosis in which the cell engulfs the molecule of drug.
often receptor mediated
no electrochemical gradient
one compartment model
all tissues and organs which the drug penetrates behaves as if they were already in equilibrium with the blood
Vd <1 =
stays in blood
Vd =-1 =
Vd > 1 =
very wide distribution
elimination is measure by?
Half-life and total body clearance
most drugs follow_____
1st order kinetics.
1st order kinetics
the rate of removal of a drug from the plasma is proportional to the concentration at a given time
chemical alteration of the drug molecule in the body which will change the physicochemical properties of the drug and its pharmacological activity
sites of biotransformation
liver, intestine, renal tubules, blood
where does biotransformation occur in the liver?
ER ---specifically the microsome
"microsomal oxidase system"
P450 system can cause what type of reactions?
oxidation, reduction, hydrolysis, and conjugation
_______ are targets for cytochrom P450 system
consequences of the P450 system
turns drug into a more water soluble form
can cause the amking of toxic or nontoxic intermdiates
______ is an inducer of the P450 system
phase I reactions
oxidation, reduciton, hydrolysis
consequences of phase I reactions:
may "flag" the drug for furthe reactions
make active or inactivate the drug
may increase or decrease water solubility
may change drug strcture
Phase II reactions:
combining a drug ot its metabolite with an endogenous substance
conjugation can occur with:
glucuronic acid---most common!
does conjugation exist in neonates?
removal or clearance of a drug out of the body
increase bld flow to the kidney = increase filtered volume
affected by milecular size and filter rate
not affect by ionization
slow compared to tubular secretion
can move against concentration gradient
NOT affect by plasma protein binding
is important for nonionized lipophilic molecules.
affected by Urine pH and glomerular filtration
highly lipophilic nonelectrolytes are ______ eliminated form teh body
how is reabsorption afect by urine pH?
change the pH will cause drug trapping and increase elmination of the drug.
how is reabsorption affected by glomarular filtration?
fluid therapy and diruteics will increase renal excretion and decrease tubular reabsorption
highly lipid soluble = metabolized first
drugs can go to teh heptic cells or the bile
criteris for going into the bile?
>300MW and polar
steriod are excreted in the_____
T or F? If there are drugs in the feces this means that there is still a chance for hte drugs to be reabsorbed?
T or F? basic drugs are excreted in milk
TRUE due to ion trapping
what the drug does to the animal
types of pharmacodynamic effects:
adverse, side, therapeutic and toxic
levels of drug action:
cell constituents that bind to an agnoist with increase affinity and trigger a cell repsonse.
most are on the cell memrbane
types of receptors:
physiological--- made for endogenous products
the increase in number or sensitivity of receptors
example of upregulation:
hyperthyroidism in cats---will cause tachycardia tdue to an increasein teh B1 receptors
decrease inteh nuber or sensitivity of receptors
causes a physiological effect. mimic
types of agonists:
produce maximal repsonse. 100% efficacy
less than maxiaml resposne <100% efficacy
drug taht binds to a spontaneousy activated cell receptor to turn it off.
acts like an antagonist
blocks the response made by agonists
types of antagonists:
binds to the receptor reversibly to prevent the agonist from binding
prevents the agonist from having an effect at any concentration due to its irreversible binding
binds to a different site than the agonist to prevent its effect
when the drug has an agonist effect onn one receptors and an antagonistic effect on another type
reversible drug-receptor binding is___
graded dosedurve measures;
ceiling, plateau, efficacy.
more important than potency.
higher the curve higher the efficacy
measured in Kd
variability in the response due to administration of the same drug does in an individual or group
variabilty in the response in the dose requried to see a measureable effect (X axis)
the smaller the dose needed to produce an effect the greater the potency
related ot the concnetration that produces Emax
can be obtained form a graded or quntal curve
the slope of the curve indicates the range of doses over which the drug acts.
shallow slope = decreased toxicity
increased slope = increased toxicity
what shape is the graded-dose curve?
agonist + antagonist on a graded dose curve will display ______
parallel shift to the RIGHT