Week 2 - Pharmacokinetics Flashcards
To produce its effect, a drug must reach…
appropriate concentrations at the site of action
2 Phases of Drug Activity Identified
- Pharmacokinetics
2. Pharmacodynamics
Pharmacokinetics
Process by which drugs are distributed within the body (drug moving in the body)
Kinesis = movement; They are absorbed, distributed, metabolized (leaving), and excreted (left)
What are the Stages of Pharmacokinetics
ADME!
Absorption
Distribution
Metabolism
Excretion
Absorption
Stage 1 of Pharmacokinetics
Drug into the blood or lymph
Ends once in the bloodstream
Distribution
Stage 2 of Pharmacokinetics
Drug goes from blood to cells and body compartments (ex: liver, bones, etc)
Metabolism
“Biotransformation”
Stage 3 of Pharmacokinetics
Alteration of Drug Structure
Direct line to the liver allows for metabolism
Excretion
Stage 4 of Pharmacokinetics
Elimination of Drug
Pharmacodynamics
process by which drugs influence cell physiology
dynamics - actions - what the drug actually does
Most drugs are absorbed how?
From the GI tract, but they can come from IV and topical sites - but in the end everything needs to end up in the bloodstream
What is the main organ for metabolism
Liver - others have capabilities but not like this
What can alter metabolism of drugs
liver damage from alcohol or hepatitis
What are the 2 major ways of excretion
Bile/Stool
Urine through the Kidneys (main one)
Drugs are stuck with __ failure
renal
When a drug permeates a cell, it must transverse…
the plasma membrane
What are 4 important considerations (chemically) for pharmacokinetics
Molecular Size and Shape (Small moves better across membranes)
Solubility - more soluble means easier to combine and move
Degree of Ionization - charged particles do not move across phospholipid bilayer easy
Concentration - things move from high to low
Permeation of cell membranes methods
Passive Process
Active Process
Facilitated Transport
Passive Process
most common form of permeation - passive diffusion and filtration
Active Process
Some drugs are actively moved with energy and a carrier making them harder or more intensive to move through the membrane
Facilitated Process
mix of passive and active
carrier mediated with no energy used and movement cannot occur against an electrochemical - required for movements that would be too slow as well like with glucose or insulin (endogenous)
What is the most common process of drug movement across membranes
passive diffusion (and filtration)
Diffusion
passive process
If the drug is water soluble, it will diffuse with the flow of water
Factors affecting Diffusion
Concentration Gradient
Lipid Solubility
Ionization
How does concentration gradient impact diffusion
things want to move from high to low until equilibrium is reached
How does lipid solubility impact diffusion
the more lipid soluble, the greater and more rapid absorption across the membrane the drug can do (distribution)
How does Ionization impact diffusion
If ionized the drug cannot cross the cell membrane as well, and this is related directly to lipid solubility
The opposite of lipid solubility
For Diffusion to occur, what factors would we like to see
Low concentration gradient on other side
high lipid solubility
low ionization
How are lipid solubility and ionization related
they are in verse of each other
the greater the ionization the less lipid soluble a drug is and vice versa
Most drugs are what kinds of acids and bases? Why?
Weak acids and bases because things too strong will cause damage
Weak Acid Drugs
tend to be un ionized in acid solution (stomach)
stay themselves in an acidic environment
Weak Base Drugs
tends to be un ionized in basic solution (intestine)
stay themselves in a basic environment
What happens to a weak acid in the intestines
it will charge/ionize and not move across membranes well - it may even just stay in the area
Filtration
simple diffusion but through channels or pores in the membrane rather than across the whole thing
Bulk flow of water will carry dissolved drugs through the channels and this allows for large molecule entrance
If molecules are too big or do not move / distribute well what may be needed?
a carrier and active transport against the concentration gradient
this can allow large and poorly lipid soluble molecules to move
Absorption is defined as
movement of the drug from site of administration into the bloodstream
Important Principle of Pharmacokinetics
Drugs must cross cell membranes and many conditions will enhance or impede the process
Pharmaceutical Phase
the first step of absorption
Dissolution
the initial rate limiting factor of drug therapy and absorption during the pharmaceutical phase
Absorption will depend on drug solubility!!!
Absorption is influenced by what factors
Drug solubility
pH
Concentration
Circulation to site of absorption
area of absorbing surface
For absorption we want drugs to be __ soluble
lipid
What sort of things can influence drug solubility
drug form
local conditions - like in GI if the stomach is full it may slow absorption since they need access to stomach wall
processing can enhance or delay - fillers, buffers, etc - these can make it work longer or be slower
pH differences important to know in the body
stomach is acidic - 1 to 2
intestine is alkaline
How does concentration impact absorption
high concentrations are absorbed faster than low ones - but we still do not want to give too much
Why is circulation important for drug absorption
more blood to carry it off for distribution and more blood in the area
What is one way to increase circulation for drug absorption
you could massage the area - like with an analgesic - to activate pressure sensors around the area so it does not hurt as much and also because the circulation to the shot site will make it work faster
this does not apply to drugs like heparin
How does temperature impact absorption
heat will increase circulation through vasodilation but cold does the opposite
What is one of the more important determinants of absorption
Area of Absorbing Surface
very large SA means a lot of medication can be absorbed
Absorbing surface is determined largely by …
ROUTE of administration
what is one the biggest absorbing surfaces
the small intestine
What is the typical natural flow of things regarding pharmacokinetic distribution?
Typically: GI Tract –> Portal Vein carries it off –> Liver –> Inferior Vena Cava –> Heart (Transportation Hub for the Body) –> General Circulation
not all drugs though
What are the routes of administration
Enteral
Parenteral
Percutaneous
Cutaneous
Enteral
This means that the route leads to the GI tract so it can be oral, rectal, etc
__ is the most common route of enteral administration
oral
Advantages of Enteral/Oral
safest (does not have to be clean/sterile)
Most economical (no equipment needed)
Most convenient
Disadvantages of Enteral/Oral
GI irritation to emesis (range - some drugs irritate causing NV)
Destruction by digestive enzymes (like insulin)’
Low gastric pH (acidic in stomach)
Irregularities in absorption (gastric bypass would change absorption of the stomach or rectal scarring)
Patient cooperation needed (cannot force)
Why is enteral/rectal usually saved a more “last resort”
poor predictability and it irritates the rectum
Parenteral
“Outside the GI Tract”
ex; shots, injections, IV
Advantages of Parenteral
absorbed in active form (no waiting for breakdown, can go right into the bloodstream)
more rapid and predictable
patient cooperation not necessary (does not need to be awake necessarily)
Disadvantages of Parenteral
asepsis must be maintained
pain
patient cannot always self medicate with this
expense - more expensive d/t equipment oftentimes
Forms of Parenteral
Subcutaneous
IM
IV
Intrathecal (right to spinal fluid)
(All bypass absorption phase and right to bloodstream)
Parenteral administration bypasses what phase of pharmacokinetics
the absorption phase (since it goes straight to blood)
Percutaneous
absorption from mucous membranes, sub lingual, or inhaled
Forms of percutaneous administration
pulmonary (gas/volatile drugs inhaled)
sub lingual (under tongue)
buccal (cheek)
other - vaginal, GU, nasal, eye ear
Cutaneous
administration via skin absorption
there is a good lipid barrier on skin so its poorly absorbed but if the skin is broken it could cause toxic dosage
skin is thick and stokes many types of drugs
Why are Children and Topical Meds Tricky
- Large skin surface in relation to body weight (lots of skin = more absorption)
- Thin dermis and epidermis leading to greater permeability (not fully developed skin barriers yet either - the child may get it faster and at a greater extent)
- Minimal lipid surface film (which blocks absorption usually)
- Skin is v prone to irritation
Nurses need to know when medications are formulated for what?
long acting or delayed release effects - these meds should not be crushed or broken as it removes the delay effect and leads to large amounts being delivered at once
Delayed Response
technically, refers to drugs w coatings that delay their release until after passing through the stomach