Pharmacokinetics
the study of how drugs enter the body, reach their site of action, and eventually become eliminated
drugs mechanism of action
once the drug reaches its target it activates biochemical and physiological events
pharmacodynamics
study of the effects and strength of a drug within the body
pharmacotherapeutics
a major study in the realm of pharmacology concerned with how drugs are used in the treatment of disease within the human body
4 processes with pharmacokinetics for a drug to reach its target
1. absorption
2. distribution
3. biotransformation
4. elimination
To produce desired effects of a drug
it must be an appropriate concentration to reach its target
active transport
the movement of materials through a cell membrane using energy
active transport achieved by
ATP (adenosine triphosphate) which is broken down into ADP (adenosine diphosphate) creating energy
Common example of active transport mechanism
sodium potassium pump (Na+ -K+), it actively moves sodium ions into the cell and potassium ions out of the cell, since it goes against the concentration gradient it uses energy
Large molecules, such as glucose and amino acids
do not pass through the cell membrane due to their size, until broken down
Large molecules move across the cell membrane
with the help from carrier proteins, found on the surface of target cells
The transport of large cells
is a process called carrier-mediated diffusion or facilitated diffusion
Once the molecule to be transported binds with the carrier protein
the cell membrane changes, allowing the large molecule to enter the target cell
Insulin
hormone created by the pancreas can increase the carrier-mediated glucose from 10- to 20-fold
Most drugs travel by passive transport
which is the movement of a substance without the use of energy
Form of passive transport
diffusion and osmosis
diffusion
involves the movement of solute in the solution
osmosis
involves the movement of the solvent (usually water)
In diffusion
solute molecules or ions move down concentration gradients from high to low
In osmosis
solvent molecules move up the concentration gradient from low to high
Final type of passive transport is filtration
movement of molecules across a membrane down a pressure gradient, from an area of high pressure to an area of low pressure. results from hydrostatic bp
drug absorption
process of movement of a drug from the site of application into the body and into the extracellular compartment
7 main factors that affect drug absorption
1. solubility of the drug
2. concentration of the drug
3. pH of the drug
4. site of absorption
5. absorbing surface area
6. blood supply to the site of absorption
7. bioavailability
solubility
tendency of the drug to dissolve
to facilitate drug absorption
the solubility of the administered drug must match the cellular constituents of the absorption site
the human body contains how much percent of water
60%
What type of drugs can penetrate lipoid (fat-containing) cells
lipid soluble (fat soluble) drugs can; water soluble drugs cannot
drugs given in water solutions
are more rapidly absorbed due the body being 60% water
concentration
drugs administered in high concentrations are absorbed much more rapidly than drugs administered in low concentrations
pH
refers to how acidic or basic the drug is, most drugs are either weak acids or weak basics
acidic drugs
tend to be more rapidly absorbed when placed into an acidic environment (like the stomach)
alkaline drugs
tend to be more rapidly absorbed when placed into an alkaline environment (like the kidneys)
site of absorption
directly affects the rate of absorption, once administered the drug must pass through many biological membranes to reach the circulation
transdermal route
A medication route generally performed by placing medication directly onto the patient's skin.
intranasal route
instilled into the nostrils, or drugs placed on mucous membranes
surface area
drugs are absorbed rapidly through large surface areas, such as inhaled medication across the vast pulmonary epithelium. some studies have shown that in some cases inhaled medications is nearly as rapid as intravenous route
blood supply to the site of absorption
some areas of the body contain more rich blood supply than others, the areas with a rich blood supply absorb more rapidly
example of rich blood supply
sublingual, under the tongue. or muscles
example of poor blood supply
fatty tissues, subcutaneous
epinephrine
1:1000, drug commonly used in acute allergic reactions, generally given subcutaneous route
Reasons for choosing subcutaneous for epi
1. it potent and concentrated, rapid absorption may cause SE such as tachycardia, trembling, hypertension
2. therapeutic effects are brief, the slow absorption prolongs the release of the drug into the circulation which maintain desired effects
systemic blood flow can affect drug absorption
such as delay of flow with shock, acidosis, and peripheral vasoconstriction. or vasodilation which will increase rate of drug absorption
comparison of rates of drug absorption
1. oral - slow
2. subcutaneous - slow
3. topical - moderate
4. intramuscular - moderate
5. intralingual - rapid
6. rectal - rapid
7. sublingual - rapid
8. endotracheal - rapid
9. inhalation - rapid
10. intraosseous - immediate
11. intravenous - immediate
bioavailability
the measure of the amount of a drug that is still active after it reaches its target
the goal of administering a drug
is to assure sufficient bioavailability to reach the target for desired effect
distribution
process whereby a drug is transported from the site of absorption to the site of action
4 main factors affecting distribution
1. cardiovascular function
2. regional blood flow
3. drug storage reservoirs
4. physiological barriers
example of regional blood flow
cardiogenic shock, blood flow to the kidneys is often diminished therefore diuretics may not reach the kidneys
reservoir
storage site for a drug, by binding to proteins present within the tissue. this action tends to delay the drug and prolong its duration
2 types of storage reservoirs
1. plasma reservoirs
2. tissue reservoirs
bound drug
portion bound to plasma proteins
free drug
unbound to plasma proteins
as soon as a drug binds to a protein
it becomes inactive, which keeps it from exerting therapeutic activity
a bound drug can free itself
to maintain a balance of bound and unbound
only free and unbound drugs
remain active
percentage of drug that remains free
depends on the amount of plasma proteins available for binding
most common plasma protein for binding
albumin, others available are hemoglobin and globulins
binding capacity
degree at which a drug is bound
common tissue reservoirs
fat, bone, and muscle
physiological barriers
inhibit the movement of certain substances while permitting the passage of others
one of the most important barriers is
blood-brain barrier
blood-brain barrier
refers to a network of capillary endothelial cells in the brain, they are surrounded by sheath of glial connective tissue that makes them impermeable to water soluble drugs
type of molecules that can enter the blood brain barrier
nonionized , unbound drug molecules such as barbiturates can enter. ionized drug molecules such as dopamine can not enter
blood brain barrier boundary
between CNS and PNS
drugs that are agonist
have both affinity and efficacy
drugs that are antagonist
have affinity but not efficacy
absorption
the process whereby a drug is moved from the site of application into the body and into the extracellular fluid compartment
affinity
the tendency of a drug to combine with a specific drug receptor
agonist
a drug or other substance that binds with a specific drug receptor and causes a physiological response
albumin
protein found in almost all animal tissue. it constitutes one of the major proteins in human blood
antagonist
a drug or other substance that blocks a physiological response or that blocks the action of another drug or substance
binding capacity
the degree to which a drug is bound to tissue or plasma protein
biotransformation
also called metabolism, is the process of changing a drug into a different form, either active or inactive, by the body
blood brain barrier
protective mechanism that selectively allows the entry of specific compounds into the brain. it is an effective boundary between the central nervous system and the peripheral nervous system
cumulative effect
a phenomenon that occurs when a drug is administered in several doses, causing an increased effect. it is usually due to a build up of a drug in the blood
distribution
process whereby a drug is transported from the site of absorption to the site of action
efficacy
power of a drug to produce a therapeutic response
elimination
process whereby a drug is removed from the body by excretion into the urine, feces, bile, saliva, sweat, breast milk, or expired air
excretion
elimination of waste products from the body. excretion is often used interchangeably with the term elimination
globulin
one of a broad category of simple proteins found in the body
half life
time required for a level of a drug in the blood to be reduced by 50 percent of its beginning level
hemoglobin
an iron containing compound found within the blood cell that is responsible for the transport and delivery of oxygen to the body cells
loading dose
initial dose of a drug given in a sufficient amount to achieve a therapeutic plasma level
maintenance dose
dose of a drug necessary to maintain a constant therapeutic plasma level
metabolism
sum total of all physical and chemical changes that occur within the body. in pharmacology it is often used interchangeably with the term biotransformation
minimum effective concentration
minimum amount of drug needed in the bloodstream to cause the desired therapeutic effect
onset of action
time interval between the administration of a drug and the first sign of its onset; onset of action is influenced by the physical and chemical properties of a drug as well as by its route of administration
pH
a scientific method of expressing the acidity and alkalinity of a solution, which is the logarithm of the hydrogen ion concentration divided by 1. the higher the pH, the more alkaline the solution; the lower the pH, the more acidic the solution
pharmacodynamics
study of a drugs action on the body
pharmacokinetics
study of how drugs enter the body, reach their site of action, and eventually are eliminated
plasma (serum) level
the amount of the drug present in the plasma. the peak plasma level refers to the highest concentration produced by a specific dose
solubility
the tendency of a drug to dissolve
therapeutic index
an index of the drugs safety profile, which is determined by calculating the difference between the drugs therapeutic threshold and toxic level. it is typically determined in the laboratory
therapeutic range
the difference between the minimal therapeutic and toxic concentrations of a drug. drugs with a low therapeutic range present a higher risk of toxicity than do drugs with a high therapeutic range. the therapeutic range is also referred to as the margin of
therapeutic threshold
the minimum amount of drug needed in the bloodstream to cause a desired therapeutic effect
toxicity
the degree to which a substance is poisonous. at high doses drugs can produce toxic effects that are not seen at low doses
toxic level
the plasma level at which severe adverse reactions are expected or likely