Pharm I exam I

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1gal =

4 L

4 L =

4000mL

1oz=

30grams

1floz =

30mL

1gr =

65mg

1kg=

1000g

drip rate

V/T x C

Vd =

dose (mg) / [in bld]

loading dose =

Vd x [desired in serum]

T1/2=

0.693/ke

CLb =

(Vd x k)/ T1/2

extraction ratio =

Ca-Cv / Ca

Clp

rate of elmination /[ drug in plasma]

rate of elmination =

urine flow x [drug in urine]

pharmacology

the sutdy of drugs on biological system

clinical pharmacology

application of pharmacological prinicpals to clinical patients

drug

any substance which can affect a biological system

therapeutic factors taht affect the administration of a drug:

onset of action
site of action
adverse reaction

drug factors that affect the administration of a drug;

ph
solubility
irritability

oral administartion

adv: safe, economical, noninfectious
dis adv: inactivation, palatability, slow onset

IV adminstration

adv: can give large volumes, accurate, and fast onet
disadv: DANGEROUS

SQ administration

adv: slow absoprtion but constant, long duration of acitivyt
disadv: slow onset

IM administration

adv: rapid onset, duration of action is longer than IV
disadv: can cause tissue damage

posology

the study of doses

dose

the amount of drug given to an animal to have an effect

dosage

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

therapeutic dose

the optimal dose, which lies between the maximal and minimal doses. has a desirabel effect

ED50

Mediam effective dose. affects 50% of the animals

LD50

meidal lethal dose. kills 50% of the animals

toxic dose

the amount that produces undesirable clinical, hematological, biochemical or pathological alterations

relative safety of drugs is calculated by:

therapeutic index
standard safety margin

therapeutic index

LD50/ED 50
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?

adrenoreceptors

dont use ______ on rabbits

TELAZOL

glucuronyl transferase

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

SNP

single nucletotid polymorphisms. in less than 1% of the population. no necessarily in a gene,and do not alwyas affect protein functions

linked SNP

"indicative SNP" are not within the gene. do not affect protein funciton.

causative SNP

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

idiosyncrasy

genetically determined unpredictable abnormal reaction to drugs.
fever, uticaria, anaphylaxis

tolerance

resistance to ordinary dose of a drug. decrease responsivness to repeated doses of same or similar drug

corss tolerance

tolerace to a drug type other than the one that induced tolerance

tachyphylaxis

acute tolerance to repeated administration of a drug.
time scale = hours

cumulation

the rate of elminiation is slower then the rate of absorption

drug-drug interaction

occurs following concurrent or sequential administration of drugs.
can be summative, synergistic, additive, or antagonistic.
can be beneficial or toxic

urine alkalizers

enhace the excretion of weak acid drugs by ion trapping

urin acidifier

enhances the excretion of weak base drugs by ion trapping

factors related to the enviornment

stress, diet, temp, humidity, oxygen

absorption

transfer of a drug from the site of injection to circulation

factors that affect absorption related ot the drug:

molecular size
lipid solubility
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
SQ<IM<IV< inhalation

factors that affect absorption related to the drug

-blood flow
-absoring surface area
-connective tissue
-species
-individual

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

gastric emptying

will determine the rate of absorption in the SI

what about an individual can impact absorption?

physiology
food presense in the GIT
diseases

diarrhea will___ absorption

DECREASE

first pass effect

drug biotransforamtion that will reduce the quantity of drug that reaches circulation.
-per os administration
-occurs due to gastric enzymes

distribution

movment of drugs from blood to tissues

what affects distribution ofa drug?

concentration
make up of the drug
steady state
protien binding
tissue binding
ion trapping

steady state

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

protein binding

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

TRUE!!

weak acids are trapped in...

basic compartments

acid compartments trap______.

weak bases

disposition

the study of the movment of drugs across biological memrbanes form the time of absorption until elmination

simple diffuion

movment from high concentration to low concentration. dependent on lipid solubility

partition coefficient

oil : water ratio
increase the ratio = increase passive diffusion

lipophilic and hydrophilic =

ETOH

hydrophobic molceules

O2 and N2

small uncharged polar molecules

urea and water
can passively diffuse

large uncharged polar molecuels

glucose and sucrose
will not diffuse

ions

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?

FALSE!

strong acid + weak base =

SALT
(Hcl, H2SO4, PO4)

strong base + weak acid =

salt
(NaOH, Ca2OH, KOH)

pinocytosis

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 =

wide distribution

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

biotransformation

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

cytochrome P450

"microsomal oxidase system"

P450 system can cause what type of reactions?

oxidation, reduction, hydrolysis, and conjugation

_______ are targets for cytochrom P450 system

lipophilic drugs

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

Phenobarbitol

phase I reactions

"nonsynthetic"
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:

"synthetic"
conjugation

conjugation

combining a drug ot its metabolite with an endogenous substance

conjugation can occur with:

glucuronic acid---most common!
sulfuric acid
glycine
glutathione
acetylation

does conjugation exist in neonates?

NO

excretion

removal or clearance of a drug out of the body

glomerular filtration

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

tubular secretion

rapid
can move against concentration gradient
carrier mediated
NOT affect by plasma protein binding

passive reabsorption

is important for nonionized lipophilic molecules.
affected by Urine pH and glomerular filtration

highly lipophilic nonelectrolytes are ______ eliminated form teh body

SLOWLY

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

hepatic excretion

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_____

BILE

T or F? If there are drugs in the feces this means that there is still a chance for hte drugs to be reabsorbed?

FALSE!

T or F? basic drugs are excreted in milk

TRUE due to ion trapping

pharmacodynamics

what the drug does to the animal

types of pharmacodynamic effects:

adverse, side, therapeutic and toxic

levels of drug action:

system
tissue
cellular
molecular

pharmacological receptors

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
drug recptors--GABA

upregulation

the increase in number or sensitivity of receptors

example of upregulation:

hyperthyroidism in cats---will cause tachycardia tdue to an increasein teh B1 receptors

down regualtion

"desensitivation".
decrease inteh nuber or sensitivity of receptors

agonist

causes a physiological effect. mimic

types of agonists:

full
partial
inverse

full agonist

produce maximal repsonse. 100% efficacy

partial agonist

less than maxiaml resposne <100% efficacy

inverse agonist

drug taht binds to a spontaneousy activated cell receptor to turn it off.
acts like an antagonist

antagonist

blocks the response made by agonists

types of antagonists:

competitive
noncompetitive
uncompetitive

competitive antagonist

"sumontable"
binds to the receptor reversibly to prevent the agonist from binding

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