Lecture # 01_Fall Flashcards
Define Pharmacokinetics
What the body does to the drug. How does concentration in blood very with dose, time.
Define Bioavailability
the relative amount of drug that reaches the systemic circulation
What is the typical bioavailability of IV drugs?
1
What is bioavailability dependent on?
- Drug absorption (want high)
2. 1st pass effect (want low)
What is “First-pass Metabolism?”
metabolism that occurs before the drug reaches systemic circulation/target site
the liver metabolizes part of an oral or rectal medication before it can reach the site of action
(less common - Other organs - ex: lungs - first pass uptake fentanyl)
T or F. Drugs have to cross the membrane in order to be active in a cell and charged particles have an easier time crossing into the cell.
False. They do need to cross the membrane to be active, but charged particles have trouble crossing
What does pKa tell you?
the pH where ionization occurs (“50-50 point”)
If the pH is more acidic than the pKa, which way will the equation be driven?
to the RIGHT
T or F. A base in a basic solution will not ionize.
True
What are the PROs and CONs of enteral medication?
Enteral = PO
PROs - easy, cheap
CONs - uneliable, need a working gut
What is an advantage of sublingual medication?
has direct absorption into systemic venous circulation, bypasses the liver, and avoids hepatic metabolism
(oral transmucosal -> veins of mouth -> SVC)
T or F. A benefit of medications given rectally is that it bypasses the liver.
Note - this was in my lecture but not your lecture notes
False…it MAY bypass the liver, but it depends on where it is absorbed.
Parenteral includes ___, ___, and ___ , and of these 3 routes, ___ is the best.
Note - this was in my lecture but not your lecture notes
IV, IM, SQ. IV is the best
Name the 4 Classic Tissue Groups
Vessel-Rich, Muscle, Fat, and Vessel-Poor
What is the % Body Weight for each of the 4 tissue groups?
Vessel-Rich - 10%
Muscle - 50%
Fat - 20%
Vessel-Poor - 20%
What % of Cardiac Output goes to each of the 4 tissue groups?
Vessel-Rich - 75%
Muscle - 19%
Fat - 6%
Vessel-Poor - ~0%
T or F. A drug must bind to protein in order for it to be available for uptake by an organ?
False. Drugs that are bound to protein are unavailable for uptake by an organ.
What protein binds to acidic drugs?
albumin
What protein binds to basic drugs?
Alpha-1-acid glycoprotein.
Would a drug be more or less effective in a malnourished person?
more effective - lower protein levels -> higher free drug levels
T or F. The effects of many anesthetic drugs terminate due to redistribution.
True
What is the formula for Volume of Distribution (Vd)?
Vd - Dose / Plasma Concentration
T or F. Drugs that are ionized and protein bound typically have a small Vd (Volume of Distribution).
True. They are usually confined to intravascular space.
T or F. Most drugs have a large Vd (Volume of Distribution) and don’t stay in the plasma.
True.
If the normal Total Body Water for an adult is ~42L, how can the Vd of fentanyl be 350L?
Fentanyl is VERY fat soluble, so it is all accumulating in the fat and the plasma concentration is very low compared to the dose given.
T or F. Elimination includes Bio-transformation and Excretion?
True
T or F. Pancuronium is very fat soluble and has a large Vd.
False. Vd= 10L and TBW is 42L
What is biotransformation?
the alteration of the drug by a metabolic process
Where does biotransformation usually take place?
Liver
Describe Phase I of Biotransformation.
Phase 1: Oxidation, Reduction, Hydrolysis -> increases polarity to make the drug water soluble for excretion in urine
What enzyme system catalyzes most of the Phase I reactions?
Cytochrome P-450 (CYP)
T or F. Because CYP activity decreases with drug exposure, overtime, less drug is required to reach the same effect.
False. It increases with drug exposure - often requiring more drugs to reach the desired effect.
T or F. Many opioids , benzodiazepines, and local anesthetics are metabolized by CYP450 enzyme system.
False. CYP3A4/5 enzyme system
What is Phase II of biotransformation?
Phase II: Conjugation with a polar substance -> water soluble for excretion in urine
Hepatic Clearance is dependent on ____ and ____.
hepatic blood flow and hepatic extraction ratio
Hepatic clearance of drugs with a high extraction ratio is limited by _______.
Hepatic blood flow (“perfusion-limited”)
What does the term “capacity-limited” indicate about hepatic drug clearance? What groups of people are effected by drugs that are “capacity-limited”?
drugs that have a low-extraction ratio and clearance is limited by hepatic function.
ppl with liver disease will be more effected by these drugs
Which of the following drugs have a low extraction ratio? A. Thiopental B. Diazepam C. Lorazepam D. All of the above
D
What are the 3 routes of excretion?
Kidneys (urine)
Bile (stool)
Lungs (mostly volatile agents, some clearance of fentanyl)
T or F. Protein bound drugs are filtered into the kidneys, are ionized in urine and are unable to be reabsorbed.
False. All is true except that it is non-protein bound drugs that are filtered into the kidneys
Define clearance.
Removal of drug from the plasma - specifically, the volume of plasma cleared of drug (by metabolism or excretion) per unit of time
T or F. Drugs must be metabolized to an inactive metabolite in order to be excreted by the kidneys.
False.
Define half-life.
time required for serum concentration to drop by one-half
What are the two compartments in the 2-Compartment Model?
Central Compartment (Plasma + VRG) and the Peripheral Compartment
T or F. The alpha phase described in the 2-Compartment Model refers to the Elimination Phase which is characterized by slower decline in drug concentration in the plasma.
False. The alpha phase is the Distribution Phase in which a quick decline occurs. The beta phase is the Elimination Phase which is characterized by slower decline in drug plasma concentration.
Does the following describe Zero-Order or First -Order Kinetics?
a fixed percentage of the drug is metabolized per unit of time for any given plasma concentration.
First order kinetics
Does the following describe Zero-Order or First -Order Kinetics?
a constant amount of drug is metabolized per unit of time, independent of plasma concentration.
Zero order kinetics
Alcohol is an example of ______-order kinetics
Zero-order kinetics
Most drugs are metabolized according to ____-order kinetics.
First-order kinetics
On a Concentration Vs. Time graph, elimination by ____-order kinetics is characterized by a straight line.
zero-order kinetics
there is zero change in the slope!
Define Pharmacodynamics
What the drug does to the body
Define Efficacy
the maximum effect a drug can cause
Define Potency
the amount of effect a drug causes for a given dose
What is ED50?
The drug dose required to produce a specific effect in 50% of the population
What is LD50?
The drug dose required to cause death (or toxicity) in 50% of the population
T or F. An ideal drug has a very narrow therapeutic index.
False.
What is the formula for Therapeutic Index?
LD50/ED50
_____ Is a diminished response to a drug due to chronic exposure.
Tolerance
______ is an acute drug tolerance after only a few doses.
Tachyphylaxis
______ antagonists bind reversibly to the same binding site as agonists
Competitive Antagonists
_____ antagonists bind to a separate binding site on the same receptor as the agonist
Non-competitive Antagonists
____ antagonists could be overcome by increasing the dose of an agonist.
Competitive Antagonists
T or F. Partial Agonists have higher efficacy than full agonists.
False. They produce a lower maximal response
Lipophilic drugs rapidly equilibrate into ____.
CNS tissue
single doses of lipophilic drugs have a ____ CNS duration of action.
short
Multiple doses of lipophilic drugs leads to increasing _____ concentrations and ____ duration of action.
peripheral tissue, longer
After multiple doses of a lipophilic drug, decrease in plasma concentration becomes dependent on _____.
drug elimination from the body
T or F. Facilitated diffusion of drugs through the lipid bilayer requires energy since carrier proteins are needed.
False. Carrier proteins are needed but requires no energy
Passive transport is typically limited by ____ not ___.
blood flow, not lipid solubility
T or F. Unlike lipophilic drugs, hydrophilic drugs need active transport to deal with concentration gradients.
False. They both do.
What age group has diminished Phase I and Phase II activities?
neonates - 1 yr
What is hepatic drug clearance?
the fraction of drug removed when blood passes through liver
GFR = ___% RBF
20%
Why is passive transport insufficient for renal drug clearance?
due to protein binding
To determine what loading dose to give, you must multiply ____ and ____.
Loading dose = Vd x target concentration
In general, do lipophilic or hydrophilic drugs have a larger Vd?
lipophilic
Why do Thiopental have a prolonged 1/2-life in the elderly?
Vd is increased
Our drugs often have a two-tailed therapeutic index. What does this mean?
There are both low (awareness) and high (overdose) “toxicities” to avoid.
What is redundancy of drug receptors?
excess of receptors. Max drug effect typically occurs at far below max receptor binding
NMJ only needs __% of receptors to be bound by Ach for clinical strength, which is why you need >___% blockage to get clinical weakness.
25%, 75%
T or F. You should ALWAYS be very familiar with the graphs on the notes because there is a good chance you will have to draw and label it on your quizzes or tests.
TRUE :)
