Principles of Pharmacology Flashcards
What is the study of drugs?
pharmacology
What is the study of drugs in human?
clinical pharmacology
What is pharmacokinetics?
what the body does to drug before it gets to site of action (what happens to the drug)
What is pharmacodynamics?
what the drug does to the body when it gets to site of action (what happens to the body) - physical response
What is the easiest place to measure what is going on with a drug?
bloodstream
What is the movement of a drug from the site of administration into plasma (time we take medication until it gets to blood stream)
absorption
What is the process of drug movement throughout the body?
distribution
What is the biotransformation of a chemical (a drug) into another chemical (metabolite)? (drug is changing by an enzyme system)
metabolism
What is the irreversible loss of a drug (or metabolites)?
excretion, or elimination
What is the acronym that describes pharmacokinetics and what does it stand for?
ADME
A: absorption
D: distribution
M: metabolism
E: excretion or elimination
What does absorption require?
crossing a biological barrier
Absorption, and therefore bioavailability, is determined by what factors?
- drug characteristics (weight, solubility)
- patient factors (muscle mass, renal and liver function, gut function)
- ability to cross membranes
**passive diffusion
**facilitated diffusion
**active transport
What describes drugs moving between “compartments” such as bloodstream, fat, muscle, etc?
distribution
What are some physical factors that determine the rate and extend of distribution?
- cardiac output
- regional blood flow
- capillary permeability (inflammation, lesions)
- tissue volume
If a patient has low cardiac output, describe the quickness of medication travel throughout the body?
slow, low travel of medications
Areas of less blood flow may receive what?
not as much drug
What describes how much drug we can get into a space?
tissue volume
Movement of dug between compartments is determined by what factors?
- drug characteristics (weight, solubility)
- membrane permeability
- binding
**plasma protein binding
**tissue binding
**fat storage
**bone uptake
The body uses what to help prevent substances from getting into certain areas to protect it from substantial harm?
membrane permeability
What are different barriers in the body that drugs would need to cross?
- blood-brain barrier (protect brain)
- blood-placental barrier (protect fetus)
- blood-testes barrier
Why is membrane permeability an important concept to consider when treating infectious illnesses?
- just because drug is effective against a specific organism does not mean it will be able to reach the site of infection
- presence of inflammation can increase permeability of a normally impermeable membrane allowing drug to penetrate (meningitis)
When you have inflammation of the meninges, what increases, and what decreases?
permeability increases, protection decreases
What is the issue with plasma protein binding?
drugs bind to proteins instead of the receptors to induce a response, so it becomes stuck to the protein and cannot become “free” to bind to its site of action
What is a saturable system due to there being only so many binding sites so competition can occur?
plasma protein binding
If two highly bound drugs are given together, what can happen?
one may displace the other resulting in toxicity (due to more drug in blood)
Competition between drugs with the same site of action is only clinically relevant when?
when the drugs are more than 90% protein bound
Albumin is the primary circulating protein that binds what?
acidic drugs
alpha1-acid glycoproteins bind what?
basic drugs
Why do you need to watch for disease states, such as dementia, where albumin levels are decreased?
- albumin levels decrease with age
- decrease in levels may lead to greater drug effects in the elderly - drug toxicity
What describes when drugs may concentrate in tissues serving as a reservoir that slowly releases drug over time?
tissue binding
What can tissue binding lead to?
increased concentration in some tissues which can lead to localized tissue (gentamicin)
What describes when lipid soluble drugs may be sequestered in adipose tissue such as oral contraceptives moving into fat spaces?
fat storage
Why do drugs stay in adipose tissues when they are sequestered there?
there is poor blood flow to fat
What can be an issue in obese patients?
storage of drugs in adipose tissue (fat storage)
What describes when drugs can be absorbed onto bone crystal surface and continue to leach out over time?
bone uptake
What situations can bone uptake of drugs be beneficial in?
in cases where the drugs incorporation in bone allows for stabilization of bone matrix
Bone uptake is harmful when considering tetracyclines, lead and radium why?
Because these things hang out in the bone and can cause damage over time
An example where a drug is given IV and concentrates in the kidneys and leads to kidney damage is an example of what?
tissue binding
What is an imaginary volume of fluid that would be required to contain the amount of drug present in the body at the same concentration as the plasma?
volume of distribution
What is Vd?
volume of distribution
What is Cpo?
plasma concentration at time it enters bdoy
How do you find volume of distribution?
amount of drug in body (dose) divided by plasma concentration (Cpo)
What is the underlying assumption of volume of distribution?
that there is a uniform distribution throughout the body, but we know that is not true
What can calculating Vd tell us?
what body compartment the drug is distributed in
Total body water accounts for how much of an adults weight?
60%
Intracellular fluid accounts for how much of an adults weight?
35%
Extracellular fluid accounts for how much of an adults weight?
25%
Interstitial fluid accounts for how much of an adults weight?
21%
Plasma accounts for how much of an adults weight?
4%
Volume of distribution says we can hold so much fluid, but sometimes we can’t, what does this mean, if Vd is greater than total body weight?
This means that some of the drug we injected has gone somewhere else, so blood levels have decreased
What is the pattern of how drugs move through the body compartments?
plasma/blood -> extracellular -> tissue/fat or intracellular
What can tell you where the drug goes, so how much is in the blood or out of the blood?
volume of distribution
How many phases to metabolism are there?
2:
- phase I
- phase II
What phase of metabolism is cytochrome drive, CYP450, and is found in the smooth endoplasmic reticulum?
phase I
What phase of metabolism is non-synthetic, so it is not breaking anything down, and includes things such as oxidation, reduction, and hydrolysis?
phase I
What are the enzymes involved in phase I of metabolism?
- 1A2
- 2B6
- 2C8
- 2C9
- 2D6
- 2E1
- 3A4
- 3A5
What is the most common enzyme in phase I metabolism responsible for over 60% of cytochrome activity (drug breakdown) and is located in the liver and gut as well?
CYP3A4
What are some reasons as to why phase I metabolism is not the same in all individuals?
- age creases phase I reactions by 30% or more
- some cytochromes may be deficient in certain populations (genetic polymorphisms)
- some disease states have altered cytochrome functioning
What can be substrates, inducers, and inhibitors?
drugs
What are metabolized by the system (enzyme works on it)?
substrate
What increases the activity of the system so metabolizing ability is increased (more of enzyme is activated)?
inducer
What decreases the activity of the system so there is a decreased ability to metabolize substances (enzyme doesn’t do its function)?
inhibitor
If inducers of an enzyme are given, what happens?
more of the drug is going to be destroyed by enzymes, so the effect of the drug will decrease
If inhibitors of an enzyme are given, what happens?
more of the drug will build up since there aren’t as many enzymes, which can lead to toxicity
What is a prodrug?
a substance that is put into the body and is inactive until it gets broken down by cytochrome and converted into something else
What may be exploited to transform a prodrug into an active substance?
cytochrome system
What % of caucasians have 2C19 and 2D6 cytochrome deficiencies?
respectively:
- 3-5%
- 6-10%
What % of asians have 2C19 and 2D6 cytochrome deficiencies?
respectively:
- 12-23%
- 1%
What % of african americans have a 2D6 cytochrome deficiency?
2-5%
If you have polymorphisms, are older, or are taking an inhibitor, what may be useless?
prodrugs because enzyme won’t be able to break it down so drug will remain in its inactive state
What phase of metabolism includes synthetic reactions and create more polar compounds allowing for excretion?
phase II
What occurs in phase II metabolism where endogenous chemical groups are attached to drug molecules via covalent bonds?
conjugation
What are glucuronidation, acetylation, sulfation apart of?
phase II of metabolism
Where does phase II metabolism occur?
cytosol
What has no effect of phase II metabolism reactions?
aging; but newborns cannot readily glucuronidate compounds
What is the most common enzyme deficiency in adults?
G6PD
What prevents some drugs from being metabolized leading to hemolysis, anemia, and possible jaundice (due to excess hemoglobin destruction)?
G6PD deficiency
G6PD deficiency has its highest prevalence in what descent?
African, Asian, and Mediterranean descent
What is slow acetylation and what can it lead to?
slow to breakdown drugs that are acetylated; can lead to toxicity
What is fast acetylation and what can it lead to?
drugs acetylated are metabolized too quickly and can lead to therapeutic failure
What describes when drugs taken orally and absorbed from the GI tract into portal vein are delivered directly to the liver where they may be metabolized before entering systemic circulation?
firs-pass effect
What results in only a fraction of the original dose being available (decreased bioavailability)?
first-pass effect
Because of phase I effects, older patients are started on what doses?
lower doses
What is the best indicator to know if someone has a genetic alteration in metabolism rate?
monitoring patient’s response
What may be metabolized prior to elimination or may be excreted as unchanged drug?
drugs
What are the primary pathways of elimination of drug?
- urine
- feces
What are some additional pathways of drug elimination?
- respiratory
- breast milk
- secretions
What are the renal pathways of elimination of drugs?
- glomerular filtration
- tubular secretion
- tubular reabsorption
What is important in glomerular filtration?
renal perfusion (blood flow - kidneys need to be receiving blood properly)
In what type of renal elimination occurs when drugs must bind to a carrier and may compete for the carrier impairing secretion and therefore elimination?
tubular secretion
What type of renal elimination depends on ionization of drug (acidity/basicity) and has the possibility that drugs in urine can be taken back up?
tubular reabsorption
Acidic drugs are excreted faster in what type of urine?
alkaline urine
Basic drugs are excreted in what type of urine?
acidic urine
What happens in biliary/fecal elimination?
- some drugs actively secreted into bile
- reabsorption may occur once in the intestine
What is it called when reabsorption of a drug occurs in the intestines?
enterohepatic recycling
What odes enterohepatic recycling do to a drug?
increases the half life of the drug
What is a common process for bile salts?
enterohepatic recycling
What is one of the most important routes of clearance and is often used to determine drug doses?
renal clearance
What is an estimate of the GFR (glomerular filtration rate)?
CrCl
What does glomerular filtration rate tell us?
how well the glomerulars work/how healthy the kidneys are
Why do we use creatinine to measure glomerular filtration rate?
because it is not secreted or absorbed
Renal filtration only filters what type of drugs?
only free drugs; bound drugs cannot do anything and cannot be filtered
Renal reabsorption favors what?
lipid soluble drugs
What do some drugs utilize to be actively secreted into the urine?
transporters
What is the primary route of drugs?
kidneys
What describes the volume of plasma cleared of drug per unit time?
clearance
How can you determine clearance?
rate of elimination/concentration
What is used in the calculations of half-life (t1/2) and steady-state (Css)?
clearance
What is proportionate to volume distribution of drugs?
clearance
What is important for determining half-life?
clearance
Where is drug metabolism via enzymes occurring primarily?
in the liver
What describes as plasma concentration increases, the drug metabolism increases?
first order kinetics
In what order kinetics is rate proportional to concentration?
first order kinetics
Most drugs go through what order kinetics?
first order kinetics
What is there a lower chance of in first order kinetics and why?
lower chance of overdose because there is a low saturation risk
What is Vmax?
maximum metabolic activity
What order kinetics has enzymes that can be saturated?
zero order kinetics
What describes as plasma concentration increases, drug metabolism stays constant?
zero order kinetics
What is the problem with zero order kinetics?
more drug is entering the system than being metabolized, can lead to toxicity
In what order kinetics is rate independent of concentration?
zero order kinetics
Constant rate of elimination is related to?
zero order kinetics
In zero order elimination, what happens to half-life as concentration decreases?
half-life decreases
In first order elimination, what happens to half-life as concentration decreases?
half-life remains constant
What is t1/2?
time to metabolize half of the drug
Knowing rate of elimination can help with what?
dosing
How many half-lives of a drug are associated with 90% of the drug being gone?
3.3 half-lives
In what order eliminations can enzymes metabolize drug more efficiently?
first order elimination
What order elimination takes longer?
zero order elimination
