Pharmacology Class 2020 Metabolism and Elimination Flashcards
Metabolism
Important for activation and termination of biological and pharmacological activity
Main site of metabolism
Liver
Active Metabolites
Product of metabolism which has pharmacologic effect such as morphin turning into morphine 6 glucurpnide
Inactive Metabolites
Product of metabolism without pharmacologic effect
Toxic Metabolites
Metabolite with harmful properties that have toxic effects.
Example:
Morphin can be broken down into MG3 morphine 3 glucuronide which can potentially buildup in a patient with renal disease which can cause seizures in patients.
Why is morphin so strong?
Because it produces strong metabolites
When does a drug have a pharmacologic effect?
When it reaches the site where it is metabolized
Prodrug
Metabolism of a prodrug produces the active metabolite
Heroin or morphine is more analgesia
Heroin because it can cross BBB.
First Pass Effect
After the drug is taken by mouth and then it goes to stomach and then gastric emptying into small intestines. It must go to portal vein before getting introduced to systemic circulation.
Metabolism can dramatically reduce concentration of drug
How does First Pass Effect affect concentration of the drug
Lowers it and therefore the drug has a weaker effect and decrease in bioavalability
Researchers want to make sure that a drug can withstand the First Pass Effect
True
How is bioavalability affected by First Pass Effect?
It decreases it
IV route of drug does not need to meet liver first before getting to bloodstream.
True or False
True
Transdermal transmit drug from dermis to bloodstream.
True or False
True
What does rectal route do in First Pass Effect?
Partial avoidance of First Pass Effect
Enterohepatic Recycling
When a drug is introduced to the liver it can recycle itself and get reintroduced back into the GI by some of the drug not being metabolized and it gets packed up with bile acid and returned back into the gut.
What is the main advantage of Enterohepatic Recycling?
Prolong’s drug’s systemic availabilty and duration of therapeutic or toxic effect.
What are the phases of drug metabolism?
Phase 1= produce active or inactive metabolites. Many Pro drugs are activated here.
Phase 1 Enzymes
Cytochrome P450 are responsible for metabolizing the majority of drugs in the liver.
Flavin Containing Monooxygenase FMO
When a drug is less polar or lipophillic due to unmasking a functional group what happens to the drug?
It is eliminated because it has less permeability which traps it for elimination.
What type of reactions occur in phase 1?
5-oxidation N-Oxidation Oxidatio Dealkylation Cytochrome P 450 dependent oxidation Epoxidation
What are the enzymes of CYP for drug metabolism?
CYP3A4
CYP2D6
CYP2C9
CYP1A2
Phase 2
Reactions involving addition of subgroups such as
Glucoronate Acetate Glithathione Glycine Su;fate Methyl Groups
All drugs go through phase 1 and phase 2.
True or False
False
What type of enzymes are phase 2?
transferases
Enzyme Induction
Acceleration of metabolism decreases levels of co administered drug.
You give two drugs together one is enzyme inducer and drug B is a substrate so drug B is chewed up more quickly.
When enzyme activity goes up then metabolism goes down.
True or False
False
What type of metabolism is beneficial to a prodrug?
Enzyme Induction
Enzyme Inhibition
Inhibition of metabolism increases levels of co administer drug increases pharmacologic action.
Drug level goes up because it is not chewed up as fast
Clearance in Excretion
The volume of plasma that is filtered of drug per unit time
Creatine Clearance
Rate of creatine removal from the plasma
More polar metabolites will enter into the urine rather than becoming reabsorbed .
True or False
True
Where do acidic drugs accumulate?
Basic side
What enhances trapping of the metabolites for excretion?
Ionizing
Where do more basic drugs accumulate?
On acidic side
What is the Gold Standard for drug dosing in accordance with creatine clearance?
Cockcroft-Gault
What must be included in the equation for Cockcroft Gault Equation if the patient is female?
multio=ply by 0.85
Area under the Curve
Describes the concentration of drug in systemic circulation as a function of time.
Elimination Kinetics
The order of a reaction refers to the way in which the concentration of drug or reactant influences the rate of chemical reaction.
First order Elimination
The amount of drug eliminated per unit time is proportional to the plasma concentration of the drug
Half Life
The amount of time that it takes for a drug concentration to decrease by 50%
What order of elimination do most drugs follow?
First order
The more extensive a drug is through the body, the more time it takes to eliminate it.
True or False
True
In first order elimination, the rate of elimination is proportional to ….?
plasma concentration
First order us also called
Linear Kinetics
Zero order Elimination
Elimination rate is fixed to an amount of drug per unit time.
Example: 20 mg eliminated per hour
Zero order Kinetics will have a half life that is not constant.
True or False
True
What happens to the half life of the drugs in zero order kinetics?
Half life will be longer for higher concentration of the drug and shorter for lower concentrations
In zero order kinetics, does increasing the drug concentration increase the metabolism or elimination of the drug?
No, because the enzymes become saturated.
The drug is eliminated independent of its concentration within the plasma.
What type of line is on the graph of zero order kinetics?
A linear line because the amount of the drug removed is constant per unit time.
Michaelis Menten Kinetics
When the enzyme responsible to metabolize a drug becomes fully saturated 100%.
What type of elimination does Michaelis Menten kinetics follow?
First order kinetics at low doses and zero order kinetics at higher doses
What happens to the half life of Michaelis Menten kinetics?
At high plasma concentrations, the half likfe will be longer.
At lower plasma concentrations the half life will be shorter.
If half life of drug A is 4 hours and what we know is what goes in is equal to what goes out?, How long?
4 hours
4 half lives
44=16
54=20
Does increasing the frequency of the drug administration affect steady state or plasma concentration?
Yes, increase
Does increasing the dose affect the steady state or concentration of a drug in the plasma?
Yes, increase
What is 100% saturation of the enzymes
zero order
Allele
An alternative form of a gene a give locus
pharmacogenetics
the study of genetic factors that underlie variation in drug response
Coding Region
A segment of a DNA sequence that is transcribed into mRNA an translated into proteins.
How much does genetics impact drug effects?
95%
What factors affect the patient’s response to the drug?
Genetics
Environment
Host Factors
Hyporeactivity
The need for unexpectedly high does for usual effect which is when a person does not become reactive to the drug at the normal dose
Idiosyncratic Reactions
Unpredicted reaction, not dependent on drug dosage, observed in a small number of patients
Dependence
The compuslive need of an indiviudal to use a drug to function normally
Tachyphylaxis
Tolerance that quickly develops over a few doses which may be due to
all spare receptors being filled
structural changes in the receptors
increased metabolism
down regulation of the receptors
What type of metabolizer is most patients classified as?
Extensive Metabolizer
What enzyme determines metabolizer status?
CYP2D6
Gene amplification
An increase in the amount of DNA in a specific region of the chromosome
Tamoxifen is a prodrug so what would happen if the drug is metabolized in a patient that is a poor metabolizer?
It would not be active because pro drugs need to be metabolized to be active drug. It must be metabilized by CYP2D6 to be turned on.
If you are a poor metabolizer of CYP2D6, what happens to the effect of codeine in the body?
Less analgesic effect and due to less active drug of codeine
