NURS 2535- Week 2

what are the 4 steps of pharmacokinetics?

1. Absorption

2. Distribution

3. Metabolism

4. Elimination

what occurs at absorption?

movement of the drug from the site of administration into the bloodstream so that it is distributed to the issues

What is the enteral route?

Administration is directly into the GI tact by oral, rectal, or NG routes

what is the fastest way to administer drugs to the bloodstream?

intravenous route (into vein)

what does p.o. mean?

administer by mouth

what does p.r. mean?

rectal route

what is a buccal route?

inside the cheek

what is a sublingual route?

under the tongue

What does parenteral mean?

by injection eg. intravenous, intramuscular, subcutaneous, intradermal, inhalation

does parenteral have a first pass effect?

no, goes directly through

what is a ID injection?

intradermal- through the dermis

what is a SC or sub Q injection?

subcutaneous- through the subcutaneous tissue layer

what is a IM injection?

intramuscular- into muscle

what is a IV injection?

intravenous injection- into vein

what is a inhalation agent?

into the lungs

what is the mechanism and drug characteristics of passive diffusion?

mechanism: high to low

characteristics: hydrophobic, small drugs

what is the mechanism and drug characteristics of facilitated diffusion?

mechanism: high to low (needs a protein carrier)

characteristics: hydrophilic, large drugs

what is the mechanism and drug characteristics of active transport?

mechanism: low to high (needs ATP)

characteristics: hydrophilic, large drugs

what is the mechanism and drug characteristics of endocytosis?

mechanism: needs receptor-mediated endocytosis then exocytosis into the vasculature

characteristics: too large

what are the factors that affect absorption?

pH, blood flow, contact time, total surface area and P-Glycoprotein

how does pH affect absorption?

the more acidic, the more easily absorbed the more alkaline (basic), the less likely to be absorbed efficiently

how does blood flow affect absorption?

⬇ blood flow decreases absorption

↑ blood flow increases absorption

how does contact time affect absorption?

if you have low contact time for eg. you have diarrhea everything will be moving quickly therefore drug cannot be absorbed

if you have high contact area eg. constipation there will be increased contact time of the drug

how does total surface area affect absorption

less surface area decreases absorption

more surface area increases absorption

How does P-glycoprotein affect absorption?

less absorption if found

if there is high absorption that means they are not present

what are the factors that affect bioavailability?

- solubility of drug

- hydrophobic vs hydrophilic

- instability of the environment

- first pass effect

What is bioavailability?

amount of drug that enters circulation

explain how the first pass effect works

- drug is administered orally

- drug circulates

- goes to liver

- drug is metabolized

therefore 30% enters bloodstream for distribution

what occurs at distribution?

drug is transported to site of action by the bloodstream

what are the factors that affect distribution?

1. blood flow

2. capillary permeability

3. protein binding

4. solubility

5. volume of distribution

what organs have increased blood flow?

brain, liver and kidneys

if certain organs have increased blood flow what would be true about drug distribution?

more drugs will be distributed to these areas

what organs have decreased blood flow?

skin and adipose tissue

if certain organs have decreased blood flow what would be true about drug distribution?

less drugs are distributed to these areas

since there is less blood flow what would be a good way to medicate skin and adipose tissue?

through topical treatments

what is capillary permeability

determines ease of fluid flow through capillary; the more permeable the easier blood passes

where is there increased capillary permeability?

liver, kidney, skin

where is there decreased capillary permeability?

muscles and brain

what is the most common blood protein?

albumin

what does albumin carry?

most protein-bound drug molecules

Where is albumin produced?

liver

what happens when a drug binds to albumin?

most will bind but some will not and the drug is considered an active and free drug

High protein bound drugs

hate floating around in water, want a taxi. over 90% bound, decreasing distribution

low protein-bound drugs

drugs that are less than 30% bound to protein which increase distribution since they are free

how does protein binding affect distribution?

Drugs need to be free to work and cross the membrane. If they are bound to proteins they cannot do this. only 30% of drugs do not bind and stay in bloodstream

What does solubility mean?

ability for drug to move easily from bloodstream across interstitial fluid and into tissues

what is the solubility and distribution of small nonpolar hydrophobic drugs?

high solubility and high distribution

what is the solubility and distribution of large polar hydrophilic drugs?

poor solubility and increased distribution

what is the solubility and distribution of drugs bound to albumin?

- poor solubility due to its charge and large size

- little distribution

What is volume of distribution?

how well a drug is distributed throughout the body based on the concentration of drug in the blood

if a drug has a low volume of distribution what is the outcome?

less penetration into tissue

if a drug has a high volume of distribution what is the outcome?

easily penetrates into tissue

what is metabolism also referred to?

biotransformation

how many phases of metabolism are there?

2 phases

Does phase I and then phase II occur for each drug?

most do but there are exceptions. some only go through one phase or phase II then phase I

what does metabolism turn drugs into?

biochemical alterations can turn drugs into:

- an inactive metabolite

- more soluble compound

- more potent metabolite

- less active metabolite

where does metabolism of drugs occur?

liver

what does metabolism help with?

excretion

what enzyme is involved in biotransformation?

enzymes (CYP450)

What does CYP450 do to drugs?

nonpolar, lipid soluble drug is oxidized or hydrolyzed by CYP450 which makes the molecule polar and water soluble

What is polymorphism?

genetic variation; may be a fast or slow metabolizer

how does polymorphism affect metabolism?

if you have a rapid metabolism you will absorb a drug faster which may cause the drug to not work or needing higher doses whereas if you are not you will absorb slower which increases risk of toxicity

What is polypharmacy?

use of multiple medications

how does polypharmacy affect metabolism?

metabolism of drugs can interfere with each other. some drugs are CYP450 inhibitors and others are inducers. inducers increases activity of enzyme therefore increase inactive metabolite and decrease active drugs. inhibitors decreases activity of enzyme therefore decrease inactive metabolite and increase active drug. can lead to toxicity

how does liver disease affect metabolism?

increases risk of toxic side effects *

how does age affect metabolism?

infants have poorly developed livers = poor metabolism

elderly have reduced rates of metabolism

what happens in phase 2 biotransformation?

already polar drug becomes even more polar

what is the end product of phase II?

a very polar, water soluble, easily excreted drug that can exit through urinary or biliary tract

What is excretion?

elimination of drugs from the body

what is the primary organ responsible for excretion?

liver

What is a half-life?

time required for 50% of drug to be removed from the body

What is steady state?

rate of drug administration equals rate of excretion

How many half lives does it take to reach steady state?

4-5

what is peak level?

highest blood level of a drug

what is trough level?

lowest blood level of a drug

what is toxicity?

occurs if peak level is too high

when do we need to do therapeutic drug monitoring?

if drug can easily become toxic

What is pharmacodynamics?

what the drug does to the body

what are the 5 mechanisms of drug actions?

1. drug receptor interactions

2. dose-response relationship

3. potency and efficacy

4. drug activity profile

5. classes of medications

what are the 2 types of drug receptors?

extracellular and intracellular

what are the 3 types of extracellular receptors?

1. ligand gated ion channels

2. g- protein coupled receptors

3. tyrosine kinase receptors

what kind of drugs have extracellular receptors?

hydrophilic, large, polar charged drugs

How do ligand-gated ion channels work?

drugs bind to receptor which has opening and closing channels allowing ions to flow in or out to get a response

How do G-protein coupled receptors work?

when a drug binds to a protein it changes the shape of the protein which activates a second messenger system which then stimulates a cellular response

How do tyrosine kinase receptors work?

when drugs target and bind to kinases to target a response

what kind of drugs have intracellular receptors?

hydrophobic, small, non-polar, uncharged drugs

How do intracellular receptors do work?

drug pass through cell membrane and binds to the receptor (takes time, slower to reach steady state)

What is the dose-response relationship?

relationship between the size of an administered dose and the intensity of the response produced (how much drug is needed to produce and therapeutic response)

What are dose response curves?

ability of a drug to produce a given physiological response

What is efficacy?

maximal therapeutic response a drug can produce.

what is potency?

amount of drug needed to produce a therapeutic response

how do you get a higher potency?

less drugs

what is a duration of action?

length of time a drug shows a therapeutic effect

What is the onset of action?

time it takes to start working

What is the therapeutic index?

ratio of minimum amt. of toxic dose to minimum amt. of therapeutic dose

what does it mean if there is a narrow TI?

higher risk of side effects and toxicity

what does it mean if there is a larger TI?

safer and less chance of toxicity

what are agonist drugs?

drugs that produce a response by mimicking ligand-receptors activation responses

what kind of response do agonist drugs produce?

full or partial

What do antagonist drugs do?

block receptors responses