Pharmacokinetics and Pharmacodynamics Flashcards
Define pharmacokinetics.
Pharmacokinetics explains the effect of the body on a drug. Determines things such as the half-life, onset and duration of effects and dosing.
What four processes are included in pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Excretion
Define pharmacodynamics.
The effect that the drug has on a specific individual.
What three principles are included in pharmacodynamics?
- MOA
- Sensitivity
- Responsiveness
What term describes a specific persons reaction to a drug which may be different than another persons reaction to the same drug
Responsiveness.
Half-life vs. Half-time
Half life is the duration of effect. So half-life of effect which encompasses all possible active metabolites of the parent compound that may prolong the duration of the parent drug. Time necessary to eliminate 50% of the drug from the BODY.
Half-time- is the how long the parent drug stays in the system. Time necessary for the plasma concentration of drug to decline 50% during the elimination phase. Independent of the dose of the drug administered.
The term used to quantify the amounts of a drug that reach the general system circulation after absorption?
Bioavailibility.
Explain clearance
plasma clearance (Cl) is the volume of plasma that is entirely cleared of the drug per unit of time.
So the units are volume/time.
cl=keVd
Ke is the rate and takes into account the summation of all routes of elimination for a particular drug.
Vd- volume of distribution (whether the drug stays in the plasma, follows total body water or concentrates in the body tissues).
Explain the basics of compartmental model of the body.
Divides the body into compartments that represent THEORETICAL spaces with calculated volumes.
Describe the basic principle of the two-compartment model.
The body is made up of two compartments. One central and one peripheral.
Describe the central component of the two-compartment model of the body (composed of, receives what % of CO, rate of uptake)
Central component contains the highly perfused tissues (kidney, liver, lungs, heart and brain)
Receives 75% of the CO
Rapid uptake of drug (IV drugs are first introduced into the central compartment, distribute to the second compartment, and then return to the central compartment for clearance)
Describe the peripheral compartment of the two-compartment model of the body.
Large calculated volume.
Extensive uptake of drug.
Fat, muscle, hair, bones, nails.
The rate of transfer between compartments decreases or increases with aging? And is dependent on what organs function?
- Decreases.
Cardiac function.
Mathematically describe the volume of distribution of a drug.
Dose of the IV drug/Plasma Concentration before elimination
What three physiochemical characteristics of a drug influence the volume of distribution? Do they increase or decrease distribution?
- Lipid Solubility increase
- Binding to Plasma Proteins decrease
- Molecular Size decrease
What happens if dosing intervals are less than the elimination half time?
Drug accumulation.
In two half times how much of the drug has been eliminated?
75%
In three half times how much of the drug has been eliminated?
87.5
In 4 half times how much of the drug has been eliminated?
93.8
In 5 half times how much of the drug has been eliminated?
96.9
In 6 half lives how much of the drug has been eliminated?
98.4
Following systemic absorption of a drug which tissues receive a large amount of the total dose?
The highly perfused ones.
Heart, brain, kidney, liver.
As the ________ decreases below that in the highly perfused tissues drug leaves the highly perfused tissues.
Plasma concentration.
When drug leaves the highly perfused tissues because of a decrease in plasma concentration where does it go? And what is this called?
less well perfused sites (muscles and fat)
Redistribution
Tissues that accumulate drug preferentially act as a what? to do what? which results in what?
A reservoir.
Maintain plasma concentration
Prolong effect
Large or repeated doses _______ inactive tissue ______ redistribution. They also prolong the ________ but by how?
saturate
negating
duration of action
effects on metabolism rather than distribution
What are the driving forces for diffusional distribution (3)?
Solubility
Concentration Gradient
Rate of Blood Flow.
Systemic absorption depends on what?
Solubility.
Name two advantages to oral administration and three disadvantages.
- most convenient
- most economic
- Emesis
- Destruction by enzymes or acidic gastric fluid.
- Irregular absorption with food or other drugs.
When drugs are absorbed from the GI system and enter the portal venous blood to travel to the liver before entering the circulation for delivery to the tissue receptors this is called? What is the result?
The first pass effect. The drug is extensively extracted and metabolized prior to entering the systemic circulation.
Sublingual/transmucosal: what type of onset? First pass effect yes or no?
Rapid onset and bypasses the liver which prevents the first pass effect.
Transdermal provides ________ therapeutic _______ of a drug.
Sustained. Plasma Concentration.
Where does absorption occur in a transdermal application?
Along sweat ducts and hair follicles.
Sweat glands and hair follicles serve as what in a transdermal application?
Diffusion shunts
What is the rate limiting step in a transdermal application?
Stratum corneum of the epidermis.
What is the stratum corneum?
Outermost layer of the skin.
What factors reflect the skins permeability for drugs?
Thickness and blood flow.
Which area has more blood flow front or back?
Front.
What can happen if the site for a transdermal application if the same site is continuously used?
Contact Dermatitis.
What makes the distal rectum different than the proximal rectum for drug delivery?
Distal rectum bypasses the portal system
Proximal rectum is transported to the portal system via superior hemorrhoidal veins meaning it undergoes the first pass effect.
The response to rectal administration of drugs is predictable or unpredictable. Why?
Unpredictable. Because of the differences in absorption of the distal and proximal rectum.
With IV administration you are able to achieve _________ precisely and rapidly?
Therapeutic plasma levels.
The lung acts as a reservoir to which kind of drugs? Give two examples.
basic lipophilic drugs
lidocaine, fentanyl and demerol
What type of drugs does the BBB prevent from crossing into the brain circulation?
Ionized, water soluble drugs
Give three instances in which the blood brain barrier can be overcome?
- Large doses of a drug.
- In head injuries
- Hypoxemia
Which type of drugs cross the BBB rapidly?
Lipophillic
In regards to acid/base, most drugs are either what? What two forms do we find them in?
- Weak acids or weak bases
2. ionized or non-ionized form
Non-ionized drugs are usually ______ soluble. Meaning what?
lipid soluble.
Meaning that they can diffuse across lipid cell membranes.
Is the non-ionized fraction of a drug pharmacologically active or inactive? Meaning what?
Active. It undergoes reabsorption across the renal tubules, is absorbed from the GI tract and is metabolized by the liver.
The ionized fraction of the drug is poorly ______ soluble. Meaning what?
lipid.
That it can not penetrate lipid cell membranes and are excreted by the kidneys unchanged.
The degree of ionization depends on what two factors?
The dissociation constant pk of a drug and the pH of the surrounding fluid.
Lower pH = more or less unprotonated acid and base?
more unprotonated acid
less unprotonated base
Higher pH = more or less unprotonated acid and base.
more unprotonated base
less unprotonated acid.
What is the significance of giving a weak acid to a person with a pH lower than the pka of the drug.
There will be more unprotonated (non-ionized) drug meaning more drug that can have an effect.
What is the term that describes the situation in which a drug can penetrate the placenta and because of the acidic environment and weak basic properties it becomes more ionized and stays there?
Ion-trapping
Describe when ion trapping occurs.
Any time that there is a concentration difference of total drug that develops on two separate sides of a membrane that separates fluids with different pHs.
Name the two most common proteins to which drug molecules bind.
albumin
alpha 1 acid glycoproteins.
The binding of a drug to plasma protein is commonly fairly _____ and the drug molecules detach ______.
Weak
Readily
Which portion of a drug that binds to plasma proteins is easily and readily available to cross the cell membranes?
The free or unbound fraction.
What kind of an effect can the protein bound portion of a drug have on the overall effect?
Lengthen the DOA.
The drug may be less potent but may have a longer effect.
Is the volume of distribution proportional or inversely proportional to protein binding?
Inversely proportional.
What types of changes in the patient could lead to a huge effect on highly protein bound drugs?
An alteration in plasma proteins. Liver disease (reduced albumin)
Name 4 highly protein bound drugs.
- Warfarin
- propranolol
- phenytoin
- Diazepam
The volume of plasma cleared of a drug by metabolism and excretion is?
Clearance
Almost all drugs administered in the therapeutic dose ranges are cleared at a first order rate. What does this mean?
At a rate proportional to the amount of drug present in the plasma.
Few drugs ______ the metabolic or excretory _______ of the body to clear drugs by first order kinetics (even at therapeutic doses) and are then cleared by zero order kinetics. What does this mean.
exceed
capacity
A constant amount of drug is cleared per unit of time. You run out of enzymes basically.
What is hepatic clearance?
The ratio of hepatic blood flow to hepatic extraction.
What is the term for when the hepatic extraction ratio of a drug is high (greater than 0.7)
Perfusion-dependent elimination. The clearance of a drug will depend on hepatic blood flow.
What does hepatic extraction depend on? Is it the same in everyone?
Enzymatic ability. It’s not the same in everyone, big part is genetics.
If the hepatic extraction ratio is low (less than 0.3) what is it called? What two factors would increase this type of clearance? What factor would not increase this type of clearance?
Capacity dependent elimination.
A decrease in protein binding or an increase in enzyme activity will increase hepatic clearance.
Changes in hepatic blood flow will have minimal changes in its clearance.
Which organ is the most important site for elimination of unchanged drugs or their metabolites?
Kidney.
When it comes to the efficiency of excretion which is more and which one is less efficiently excreted by the kidney? Water soluble compounds or lipid soluble.
More-water soluble
Less-lipid soluble
Which type of drugs are reabsorbed such that little or no unchanged drug is excreted in the urine?
Highly lipid soluble.
Are water soluble drugs ionized or non-ionized?
Ionized.
How are highly lipid soluble drugs excreted?
They have to be metabolized into water soluble metabolites.
The process by which pharmacologically active, lipid soluble drugs are converted into water soluble and often inactive drugs is called?
Biotransformation.
Increased ___________ reduces the volume of distribution for a drug and enhances it’s renal excretion.
water solubility
Why is metabolism not always synonymous with inactivation or detoxification?
Because some metabolites of certain drugs are active.
Name a drug that has an active metabolite?
Morphine
Ketamine
Versed
Describe first order kinetics in regards to metabolism.
It is the most common form of metabolism. When a constant fraction of an available drug is metabolized in a given time period.
Describe zero-order kinetics in regards to metabolism.
Plasma concentration of the drug exceeds the capacity of the metabolizing enzymes. Metabolism of a constant amount of a drug per unit of time.
Name the four pathways of metabolism.
- Oxidation
- Reduction
- Hydrolysis
- Conjugation.
Drugs that undergo phase 1 metabolism are involved in what type of reactions.
Oxidation, reduction and hydrolysis.
Drugs that undergo phase 2 metabolism are usually involved in what type of reactions?
- Conjugation where the parent or a metabolite drug reacts with an endogenous substrate to form water-soluble conjugates.
Name 5 sites where metabolism of drugs occurs.
- Plasma
- Kidneys
- Lungs
- GI tract
- Liver
Which is the biggest site for metabolism? And what is responsible?
The liver.
Hepatic microsomal enzymes are responsible.
Where are hepatic microsomal enzymes located?
Smooth ER
What is the Cytochrome P-450? Where is this group?
A large number of different protein enzymes involved in oxidation, reduction and conjugation of a large number of drugs. IN THE LIVER.
What is enzymatic induction?
When drugs and chemicals stimulate the activity of enzymes required for metabolism.
How do nonmicrosomal enzymes metabolize drugs?
Mostly by conjugation and hydrolysis.
Where are non-microsomal enzymes present?
Liver, plasma, GI tract.
Non-microsomal enzymes are required for the hydrolysis of drugs containing what?
Ester bonds.
Name two specific drugs that are metabolized by nonmicrosomal enzymes.
Succhs and esmolol
Do we see enzymatic induction in nonmicrosomal enzymes?
No
What determines nonmicrosomal enzymes?
Genetics.
The most common mechanism by which drugs exert pharmacologic effects is through interaction with?
specific macromolecules in the lipid bi-layer of cell membranes called RECEPTORS!
Response to specific stimuli could possibly do what to the concentration of receptors?
up regulate or down regulate
Describe the state of receptor activation theory.
The non-activated receptors are converted to active by the drug.
Describe the receptor occupancy theory.
The more receptors occupied by a drug the more effect.
The affinity of a drug for a specific macromolecular component of the cell and its intrinsic activity are intimately related to?
The drugs chemical structure.
Minor changes in the chemical structure of a drug could result in?
Major changes in it’s pharmacological properties.
What can be produced by sp3 hybridized carbon atoms?
Enantemerism
When free rotation about the chiral carbon is not possible, how many stable forms of the molecule can exist?
Two.
Does interaction with a biological receptor differ between two enantomers?
Yes, greatly even to the point of no binding. Some isomers may cause side effects or entirely different effects than it’s mirror image.
If each chiral carbon can exist as two molecules in nature a molecule with two chiral carbon centers has how many isomers?
4.
People in whom an unusually low dose of drug produces its expected pharmacologic effect are termed?
Hyper-reactive
Explain the principle behind an additive effect. Is it predictable?
The second drug acting with the first will produce an effect equal to the sum of both. Yes, it is predictable
Explain the principle behind a synergetic effect.
Two drugs interact to produce an effect greater than their sum.
Name a pair of drugs that when given together have a synergetic effect.
Versed and Fentanyl.
