Apex-Pharmacokinetics Flashcards
What measures the relationship between a drug dose and a drugs plasma concentration?
Volume of Distribution
What is a theoretical measure of how a drug distributes throughout the body?
Volume of distribution
What does Vd (volume of distribution) assume? (2)
- That the drug distributes instantaneously &
- That the drug is not subject to biotransformation or elimination before it’s fully absorbed
Do hydrophilic drugs have a low or high Vd?
Low > they distribute into some or all of the total body water but don’t distribute into fat
Do hydrophilic drugs require higher or lower doses to achieve a given plasma concentration?
Lower doses (they are restricted to the ECF and stay there - don’t have to worry about their distribution into fat which would require more drug to get to a certain plasma concentration)
Example of high vs low Vd drugs? (1 each)
High = propofol (distributes into fat, lipophillic)
Low = neuromuscular blockers (stays in the ECF)
Volume of Distribution = (2 calculations)
Amount of drug/Desired plasma concentration
Patients weight x Vd of a given drug
How to calculate a loading dose
Vd x Desired plasma concentration/Bioavailability
What is the bioavailability of all IV drugs?
1
> bc 100% of it is immediately available in the ECF (doesn’t have to go through 1st pass metabolism in the liver)
Total Body Water = ____L or _____L/kg
42 L
0.6L/kg
(High/low) Vd drugs exceed total body water
High (Lipophilic)
What makes up total body water?
The ECF - 14L & ICF 28L
60%/40%/20% (15%/5%)
T-I-E
70kg always normal reference
40% x 70kg = 28L
20% x 70kg = 14L
What makes up ECF?
60/40/20 (15/5)
Intesistial = 15% (10.5L)
Plasma = 5% (3.5L)
% of 70kg
Define drug clearance
The volume of PLASMA that is cleared of the drug over time
What are the major clearing organs? How are drugs cleared in the plasma?
Liver and Kidney
Hoffmann elimination and ester hydrolysis in the plasma
What is the term for when the amount of drug entering the body = the amount of drug leaving the body
Steady state
How many half-times must elapse to achieve steady state?
5
Clearance is directly proportional to (3)
- Blood flow to the clearing organ
>more blood flow to the kidney = faster the drug can be cleared - Extraction ratio
>more extraction = more cleared - Drug dose
>increased drug = increased clearance
Clearance is (indirectly/directly) proportional to:
Half life vs drug concentration in the central compartment
Both inversely related
- Half-life
>increased 1/2 life = decreased clearance - Drug concentration in the central compartment
>more drug in the central compartment = less being cleared
In multi-compartment models, what do the Alpha and Beta phases represent ?
Alpha phase = distribution (plasma concentration decreases)
Beta phase - represents drug elimination from the central compartment
Elimination half-life vs half-time
Half life = time required for a drugs plasma concentration to decrease 50%
>the time it takes for 50% of the drug to be removed from the body
Half-time = The time it takes for 50% of the drug to be removed from the PLASMA during the elimination phase (think- watch 1/2 TIME show on PLASMA tv)
> this oversimplifies the movement of drug inside the body and is clinically meaningless
What is the term for the time required for the plasma concentration to decrease 50% after an infusion has stopped?
Context-sensitive half-time
When is a drug considered to be cleared from the body?
When 96.9% of it has been eliminated from the plasma (5 half-times)
Filling out half-time table
First row 0-5
%Drug eliminated
%Drug remaining
Label the opioids on the context-sensitive half time chart
FASteR
A weak acid/base is where the pH of a solution is (>) the pKa of the drug?
Weak acid : pH of solution < pKa of the drug (decreased pH =acidic)
Weak base: pH of solution > pKa of the drug (increased pH = basic)
*more likely to pass through a lipid membrane
What is the difference between a weak acid and a weak base?
Weak acids donate a H+
Weak bases donate OH-
What happens when the pKa & pH of the drug are the same?
50% will be ionized and 50% will be unionized
What is ionization?
The process where a molecule gains a positive or negative charge, affecting it’s ability to diffuse through lipid membranes
Amount of ionization a drug undergoes depends on what 2 factors?
The solutions pH and the pKa of the drug
Another name for pKa
Disassociation constant
Ionized vs un-ionized:
Water/lipid soluble
Pharmacologically active/inactive
Hepatic biotransformation vs renal elimination more likely
Diffuse across lipid bilayers - yes/no
Ionized = water soluble , pharmacologically inactive, renal elimination more likely, does not diffuse across lipid bilayers (likes the water and stays there)
Un-ionized = lipid soluble, pharmacologically active, hepatic biotransformation more likely, yes diffuses across lipid bilayers (BBB, GI tract, Placenta)
Does albumin carry a positive or negative charge?
Will it primarily bind acidic or basic drugs?
Negative charge
-will primarily bind acidic drugs (+/-)
Does alpha-1 acid glycoprotein primary bind basic or acidic drugs?
Basic drugs
Does beta-globulin bind acid or basic drugs?
Basic
(Beta, Basic)
5 circumstances where albumin will be decreased (increased risk of toxicity)
- Liver disease (liver makes albumin)
- Renal disease (albumin passes through diseased kidneys)
- Old age
- Malnutrition (ETOH)
- Pregnancy (altered distribution)
5 circumstances where alpha-1 acid glycoprotein would be increased and 2 for decreased states
Increased = surgical stress, MI, chronic pain, RA, old age
Decreased = neonates and pregnancy
If a drug is 98% bound and the bound fraction decreases to 96%, how much has the unbound or free-fraction of the drug increased by?
100%
(2% free increases to 4% free)
(4-2)/2 x 100 = 100%
Zero order kinetics vs First-order kinetics
Zero order = a constant AMOUNT of a drug is metabolized over time
First- order = a constant FRACTION (F/F) of a drug is metabolized over time