Transcript Pharmacokinetics and pharmacodynamics

PHARMACOKINETICS AND
PHARMACODYNAMICS
CH 3
INTRODUCTION
• Pharmacokinetics: the study of how a drug moves into, through, and out of the body
• How is it absorbed into the body, where is it distributed to, how it is metabolized, how is it
eliminated
• Think: what happens to the drug while it is in the body?
• Pharmacodynamics: the study of how the drug produces its effects on the body
• What tissues are effected/what changes are made because of the drug
• Think: what happens to the body because of the drug?
• Therapeutic range: ideal range of drug concentrations
in the body.
• Also called the therapeutic window
• The manufacturer's dose should achieve concentrations in
the therapeutic range.
• Too much drug will make concentrations in the body
exceed the top of the therapeutic range (maximum
effective concentration)
THERAPEUTIC
RANGE
• Insufficient drug amounts will cause the concentration of
drug in the body to be below the therapeutic range
(minimum effective concentration)
• To maintain a drug’s therapeutic range, the amount of
drug entering the body must be balanced with the rate
that the drug leaves the body.
THERAPEUTIC INDEX
• Therapeutic index: the comparison between a drug’s
ability to produce the desired effect and its tendency to
produce toxic effects.
• Expressed as a ratio between the LD50 and the ED50
• LD50= dose of a drug that is lethal in 50% of animals in the
clinical trial
• ED50= dose of a drug that is effective in 50% of animals in the
clinical trial
• TI= LD50/ED50
• The larger the TI, the safer the drug
DOSAGE REGIMEN AND
ROUTES OF ADMINISTRATION
• Dose, dosage interval, and route of administration are the three components of the
therapeutic administration of drugs
• Dose: the amount of drug administered at one time
• LOADING DOSE: amount of drug designed to raise the drug concentration to the
therapeutic range in a short time.
• Larger than the maintenance dose.
• Administered as either a large amount once or small amounts frequently.
• Used in situations where achieving the effect of the medication quickly is critical
• MAINTENANCE DOSE: maintains therapeutic concentrations established by the loading
dose.
• Smaller than the loading dose
DOSAGE REGIMEN AND
ROUTES OF ADMINISTRATION
• Dosage interval: time between administrations of separate drug doses
• Once daily dosage interval produces a wide swing in drug concentrations (high
concentration after the drug is absorbed, possibly toxic, and a low concentration right
before the next dose, possibly subtherapeutic).
• More frequent dosing results in less of a difference in drug concentrations throughout the day. This
option would also be more likely to result in concentrations in the therapeutic range.
• Total daily dose: the combined amount of drug (in mass) administered in a given day
• Ex: 100 mg would be the total daily dose of a 25mg tablet was given every six hours. The
total daily dose would be the same if it was a 50mg tablet given BID.
DOSAGE REGIMEN AND
ROUTES OF ADMINISTRATION
• Route of administration: the means by which a drug is given.
• Parenteral: a route that does not involve the GI tract (ex: injection)
• Intravenous: drug is injected directly into a vein. It is carried toward the heart where it is
diluted before being distributed throughout the body.
• IV bolus- single, large volume injected at once
• IV infusion- drug is slowly injected (dripped) into a vein over second, minute, or hours. Results in a
steady accumulation of drug concentrations in the body until the drug concentrations plateau
(steady state)
• The accidental injection of an IV drug outside the vein is termed extravascular or perivascular.
• Intra-arterial: drug is injected directly into an artery. It is carried toward a specific organ or
tissues at high concentrations
DOSAGE REGIMEN AND
ROUTES OF ADMINISTRATION
• Intramuscular: drug is injected directly into a muscle
• Subcutaneous: drug is administered beneath the skin
• Intradermal: drug is administered within the skin
• Intraperitoneal: drug is administered within the abdominal cavity
• Per os: drug given by mouth
• Topical: drug administered on the surface of the skin
• Aerosol: drug is administered in an inhaled mist or gas and absorbed into the airways
• PASSIVE DIFFUSION: the random movement of drug molecules
from an area of high to low concentration
• Down the concentration gradient.
• The majority of drug movement through tissue fluid or membranes
occurs this way. Drug moves from the site of administration (high
concentration) to other areas of the body (low concentration).
• Once equilibrium is achieved, the drug molecules may still move,
but will do so evenly throughout the tissues.
MOVEMENT
OF DRUG
MOLECULES
• No energy is used.
• For a drug to diffuse across the phospholipids of a membrane, it
must be able to dissolve in fat (since cell membranes are made of
phospholipids).
• FACILITATED DIFFUSION: diffusion across a cell
membrane that involves a carrier molecule within the
membrane.
• Protein with receptor sites for drug molecules
MOVEMENT
OF DRUG
MOLECULES
• When a drug molecule fits into the receptor, the carrier
protein changes to allow the drug to pass across the
membrane (no dissolving required)
• No energy needed (passive process)
• Direction of movement is down concentration gradient
• ACTIVE TRANSPORT: Carrier protein assists in moving the
drug molecules across the membrane without the
limitations of a concentration gradient.
• Energy is required
• Does not result in an equal amount of drug molecules on
each side of the membrane
MOVEMENT
OF DRUG
MOLECULES
• Less common method of movement
• PINOCYTOSIS: Part of the cell membrane forms an
invagination to take in drug molecules (cell drinking)
• A form of active transport that is not often used
• Slow process because the cell membrane has to change
its shape
MOVEMENT
OF DRUG
MOLECULES
• PHAGOCYTOSIS: Part of the cell membrane
surrounds/engulfs the drug molecules (cell eating)
• A form of active transport that is not often used
• Slow process because the cell membrane has to change
its shape
MOVEMENT OF DRUG MOLECULES
• Factors that affect rate of drug molecule transport:
• Facilitated diffusion and active transport
• Number of carrier proteins available
• Diffusion
• A large the concentration gradient makes drug molecules move quickly
• Drug molecule size (smaller will move faster)
• Lipophilic molecules will be able to dissolve within the membrane quickly. Hydrophilic
molcules will require a carrier protein
• The higher the temp, the faster the diffusion rate
• The thicker the membrane, the slower the diffusion rate