Apex Unit 4 Flashcards
Define volume of distribution, and recite the equation.
The volume of distribution (Vd) describes the relationship between a drug’s plasma concentration following a specific dose. It is a theoretical measure of how a drug distributes throughout the body.
Vd assumes two things:
The drug distributes instantaneously (full equilibration occurs at t = 0).
The drug is not subjected to biotransformation or elimination before it fully distributes.

What are the implications when a drug’s Vd exceeds TBW? What if Vd is less than TBW?
If Vd > TBW, the drug is assumed to be lipophilic:
It distributes into TBW + fat.
It will require a higher dose to achieve a given plasma concentration.
Examples: propofol, fentanyl
If Vd < TBW, the drug is assumed to be hydrophilic:
It distributes into some or all of the body water, but it does not distribute into fat.
It will require a lower dose to achieve a given plasma concentration.
Examples: NMBs (ECF), albumin (plasma)
How do you calculate the loading dose for an IV medication?
How about a PO medication?
For an IV drug, the bioavailability is always 1. This is because all of the drug enters the bloodstream.
A drug administered by any other route may not be absorbed completely and/or it may be subjected to first pass metabolism in the liver. These conditions reduce bioavailability and explain why the dose that achieves a giv

What is clearance? What factors increase/decrease it?
Clearance is the volume of plasma that is cleared of drug per unit time.

What is steady state?
Steady state occurs when the amount of drug entering the body is equivalent to the amount of drug being eliminated from the body – there is a stable plasma concentration. Each of the compartments has equilibrated, although the total amount of drug may be different in different compartments.
(SS) Rate of Administration = Rate of Elimination
Steady state is achieved after 5 half-times.
Compare and contrast the alpha- and beta distribution phases on the plasma concentration curve.
The plasma concentration curve graphically depicts the biphasic decrease of a drug’s plasma concentration following a rapid IV bolus.
Alpha distribution phase:
Describes drug distribution from the plasma to the tissues.
Beta distribution phase:
Begins as plasma concentration falls below tissue concentration.
The concentration gradient reverses, which causes the drug to re-enter the plasma.
The beta phase describes drug elimination from the plasma by the clearing organs.

You have administered 30 mg of esmolol to a patient after a sudden (and profound) elevation in heart rate. After three half-lives, what percentage of your initial dose remains in the patient’s bloodstream?
12.5% of the drug remains in the patient’s bloodstream.
The half-time is the amount of time required for the drug concentration to decrease by 50%. You must know this chart!

What is context sensitive half-time?
The problem with half-times is that they do NOT consider time.
The context sensitive half-time solves this problem. It is the time required for the plasma concentration to decline by 50% after discontinuing the drug.
Discuss the context sensitive half-times of fentanyl, alfentanil, sufentanil, and remifentanil. Which has the longest? Which has the shortest? Why?
The context-sensitive half-time for a fentanyl infusion increases as a function of how long it was infused. A longer infusion had more time to fill up the peripheral compartments, therefore more fentanyl has to be eliminated and it will have a longer elimination half-time. This is also true for alfentanil and sufentanil to lesser degrees.
Remifentanil is an exception. Even though it is highly lipophilic, it is quickly metabolized by plasma esterases and has a similar context-sensitive half-time regardless of how long it is infused.

What is the difference between a strong and weak acid or base?
what is the equation?
The difference is the degree of ionization:
If you put a strong acid or a strong base in water, it will ionize completely.
If you put a weak acid or a weak base in water, a fraction of it will be ionized and the remaining fraction will be unionized.

What is ionization? What 2 factors determine how much a molecule will ionize?
Ionization describes the process where a molecule gains a positive or negative charge.
The amount of ionization is dependent on two things:
The pH of the solution
The pKa of the drug
Finish this sentence: When pKa and pH are the same, _______________________________.
50% of the drug will be ionized and 50% will be unionized.
How does ionization affect solubility, pharmacologic effect, hepatic biotransformation, renal elimination, and diffusion across lipid bilayers?

What happens when you put an acid in a basic solution?
How about an acidic solution?
Remember that “like dissolves like”
An Acid in a Basic Solution:
An acidic drug will be highly ionized in a basic pH.
The acidic drug wants to donate protons and the basic solution wants to accept protons.
The acidic drug happily donates its protons and will become ionized.
An Acid in an Acidic Solution:
An acidic drug will be highly unionized in an acidic pH.
The acidic drug wants to donate protons and the acidic solution wants to do the same.
Since there are no proton acceptors, the acidic drug retains its proton and will remain unionized.
Can you tell if a drug is an acid or a base by looking at its name? If yes, how?
Most drugs are weak acids or weak bases. They are usually prepared as a salt that dissociates in solution.
A weak acid is paired with a positive ion such as sodium, calcium, or magnesium.
Example: Sodium thiopental
A weak base is paired with a negative ion such as chloride or sulfate.
Example: Lidocaine hydrochloride, morphine sulfate
Name the 3 key plasma proteins. Does each bind acidic drugs, basic drugs, or both?
Albumin primarily binds to acidic drugs, however it also binds to some neutral and basic drugs.
α1-acid glycoprotein binds to basic drugs.
Beta-globulin binds to basic drugs.
What conditions reduce albumin concentration?
Liver disease
Renal disease
Old age
Malnutrition
Pregnancy
What conditions affect α1-acid glycoprotein concentration?
Increased α1-acid glycoprotein concentration:
Surgical stress
Myocardial infarction
Chronic pain
Rheumatoid arthritis
Advanced age
Decreased α1-acid glycoprotein concentration:
Neonates
Pregnancy
How do changes in plasma protein binding affect plasma drug concentration?
Decreased PP binding → Increased Cp
Increased PP binding → Decreased Cp
How do you calculate changes in plasma protein binding?
[Free drug] + [Unbound protein binding sites] ↔ [Bound drug]
If a drug is 98% bound and the bound fraction is reduced to 96%, the unbound or free fraction has increased by 100%! Said another way, if the free fraction is 2% and it increases to 4%, then the free fraction has increased by 100%.
***You must calculate the percent change to complete this calculation***
A new anesthetic drug is cleared from the body at a rate proportional to its plasma concentration. What kinetic model best describes the elimination of this drug?
First-order kinetics: A constant fraction of drug is eliminated per unit time.
Most drugs follow this model.

Alcohol is cleared from the body via zero-order kinetics. How will this drug’s rate of elimination change as plasma drug concentration changes?
Under zero-order kinetics, a constant amount of drug is eliminated per unit time. Said another way, the rate of elimination is independent of plasma drug concentration.
Other examples: aspirin, phenytoin, warfarin, heparin, and theophylline

What is the function of a phase 1 reaction? List 3 examples.
Phase 1 reactions result in small molecular changes that increase the polarity (water solubility) of a molecule to prepare it for a phase 2 reaction – it creates a location on the molecule that will allow the phase 2 reaction to take place. Most phase I biotransformations are carried out by the P450 system.
There are 3 phase I reactions that you should understand:
Oxidation – adds an oxygen molecule to a compound
Reduction – adds electrons to a compound
Hydrolysis – adds water to a compound to split it apart (usually an ester)
What is the function of a phase 2 reaction? List 5 common substrates.
The phase 2 reaction conjugates (adds on) an endogenous, highly polar, water soluble substrate to the molecule. This results in a water soluble, biologically inactive molecule ready for excretion.
Common substrates for conjugation reactions include: glucuronic acid, glycine, acetic acid, sulfuric acid, or a methyl group.
Some drugs do not require preparation by phase I reactions and may proceed directly to phase II reactions.
























