lecture4&5 Flashcards
what form of an acid can transverse the membrane
the protonated form
what form of a base can transverse a membrane
the unprotonated form
what does the Henderson Hasselbalch equation tell us about drugs
it will give us a clue as to how much is protonated and so how much of the acid can transverse the membrane
where do weak acids get absorbed
more likely in the stomach
where do weak bases get absorbed
more likely in the intestines
what cardiac factors impact distribution
cardiac output, regional blood flow, capillary permeability, binding to plasma proteins.
what are the four main factors of distribution
cardiovascular, tissue binding, drug molecule size, and lipid solubility.
what is biotransformation
reaction or metabolism of drugs can be categorized as phase 1 or phase 2. these can convert a parent compound into an active or inactive metabolite.
what is phase 1 biotransfromation
generates a more polar molecule by exposing a functional group on parent group readies for phase 2 FORMS METABOLITE ACTIVE OR NOT
what is phase 2 biotransformation
reaction yield a more water soluble conjugated product to be excreted. CONJUGATED
what kind of reactions happen in phase1
oxidation reductive and hydrolytic
what kind of reactions happen in phase2
glucuronidation, sulfation, acetylation, methylation,
what is the first pass effect
that drugs absorbed by stomach or intestine will be carried by portal vein to the liver.
what is the primary mechanism of drug elimination
renal excretion
what processes effect renal excretion
GFR binding to plasma proteins, alklinization or acidification of urine
what is another route for more lipophilic drugs to be excreted
fecal excretion
what are the key parameters that impact drug dosage in patients
volume of distribution and clearance
what is volume of distribution
the measure of the space in the body available to contain the drug. This is a theoretical number
what is clearance
measure of the ability of the body to eliminate a drug
what is volume of distribution as a formula
V=amount of drug in body/concentration of drug in blood or plasma. A high volume suggest the drug is moving but a low volume suggests little movement.
what is the formula for clearance
CL=rate of elimination/concentration
what is zero order elimination
this is when the elimination process is at capacity or saturated, so its independent of concentration. Linear on a normal scale nonlinear on a log scale
what is first order elimination
non saturated process you will remove a fraction of the drug is removed every time period. Ie 50% every two hours non linear on a normal scale linear on a log scale
what is flow dependent elimination
an organ has a high capacity but needs the right flow to get the drug there. Looks like first order kinetics
what is capacity limited elimination
a point where the drug has saturated the elimination capacity of the system, but in dosage exceeds elimination this could lead to toxicity. Looks like zero order kinetics
how does volume of distibution effect half life
the larger the volume of dist. The longer the half life
how does clearance effect half life
the slower the clearance the longer the half life of the drug.
what is the acuumulation factor
AF=1/fraction lost in one dosing interval. Only works if dosing is less than four half lives.
what is the bioavailability
the amount of drug that reaches the systemic circulation. IV will be 100%
what is the extraction ratio formula
ER= clearance of liver/hepatic blood flow or Q. the close to 1 the more its extracted and less is available.
what is the bioavailability formula
F=extent of absorption of the gut or f, x [1-ER]
what is steady state concentration Css
the point where what is reaching the blood is what is leaving the blood
what is the formula for steady state
Css=dosing rate/Clearance or CL ti will take 4-5 half lives to reach the Css and is independent of the dose and dosing rate and only dependent of the half life of the drug.
what is the maintenance dose
dose needed to maintain a steady state concentration in order to determine a maintenance dose the dosing rate must first be determined.
what is the formula for dosing rate
ClxTC or target concentration this is for an IV dose, for oral does it would be Dosing rate/ F oral or bioavalibility
what is the formula for maintenance dose
dosing rate x Dosing interval
what happens to concentrations as the dosing interval increases
it will increase the peak and decease the trough concentrations which might or might not effect the patient.
what is the loading dose
an initial dose that can be given in order to achieve the target concentration rapidly.
what is the formula for loading dose
LD=V x TC / F
how many half lives does it take for a drug concentration to be considered negligable?
4-5 half lives.
