|
Pharmacokinetics
|
the study of drug movement through the body. The effect of the body on the drug.
|
|
|
Absorption
|
the movement of a drug from its administration site into the circulation
|
|
|
Rate of Absorption
|
how soon the effects of a drug will begin
|
|
|
Amount of Absorption
|
intensity of the drugs effects
|
|
|
Factors affecting absorption
|
rate of dissolution, surface area, blood flow, lipid solubility, pH partitioning,
|
|
|
Rate of dissolution
|
drugs in formulations that have rapid dissolution have a faster onset than drugs with slower rate of dissolution
|
|
|
Surface Area
|
the larger the surface area the faster the absorption. Small intestine has fastest absorption of oral administered drugs
|
|
|
Blood Flow
|
the more vascular a site the quicker the absorption. Works on concentration gradient, blood containing newly absorbed drug will be replaced rapidly by drug free blood.
|
|
|
Lipid Solubility
|
Highly lipid soluble drugs absorb more rapidly.
|
|
|
pH partitioning
|
drug absorption and elimination ca be affected by acid/base concepts. Also works on concentration gradient. Acid drugs are drawn toward alkaline and vice versa. Important in treatment of overdoses.
|
|
|
Routes of administration
|
enteral and parenteral and less commonly topical etc.
|
|
|
Enteral Administration
|
via the gastrointestinal tract
|
|
|
Parenteral Administration
|
drugs given by penetration of the skin and entry into the underlying tissue
|
|
|
IV
|
rapid effect maximal degree of control over circulating drug. Usually aqueous. Not reversible.
|
|
|
Drawbacks of IV
|
Infection, repeat dosage requires patent iv line.
|
|
|
IM
|
May be used for drugs that are aqueous and non-aqueous. Deltoid and Vastus lateralis quicker than dorso-gluteal or ventro-gluteal admin. Related to blood flow to tissue
|
|
|
Subcutaneous
|
Dependent on blood flow to the tissue. Slow and constant absorption, non-irritating requires absorption into capillaries.
|
|
|
Oral
|
most common. Variable in terms of availability. Efficacy may be limited by metabolism. Food in system may affect efficacy/action or delay gastric emptying leading to destruction of drugs.
|
|
|
Distribution
|
The movement of drugs throughout the body. Dependent upon blood flow to tissues, the availability of the drug to exit the vascular system and to a lesser extent, the ability of the drug to enter the cells.
|
|
|
Speed of Blood flow
|
Well perfused organs such as brain, heart, kidney and liver receive most of the drug in the first few minutes. Muscle, most viscera, skin and fat are slower to receive drug, from minutes to hours.
|
|
|
Diffusion into Interstitial Compartments
|
rapid diffusion occurs in most areas because of permeable capillaries. E.g.. Liver capillaries have much of basement membrane exposed by slit junctions which enables rapid diffusion including large plasma proteins.
|
|
|
Blood brain Barrier
|
no slit junctions in brain so drugs must either pass directly through (lipid soluble) or via active transport.
|
|
|
Biotransformation
|
Drug metabolism. The most important consequence of metabolism is promotion of renal excretion.
|
|
|
Most important factor in biotransformation
|
Renal excretion
|
|
|
Factors affecting biotransformation
|
Induction, first pass effect, extremes of age, nutritional status, competition among drugs.
|
|
|
Induction
|
Some drugs, acting on the liver, can increase the rate of their own or another drug's metabolism. E.G.. Phenobarbital the classic enzyme inducer
|
|
|
First Pass
|
rapid inactivation of oral drugs due to liver metabolism.
|
|
|
Metabolism relating to lipophilic drugs
|
Lipophilic properties that promote a drug's passage through biologic membranes and subsequent access to their sites of action also hinders elimination of the drug.
|
|
|
Usual biotransformation of drugs
|
usually biotransformed into more polar, inactive metabolites that are easily excreted by body.
|
|
|
Hepatic Metabolism
|
Metabolites with increased biologic activity or even toxic properties may be created through metabolism E.G.: Tylenol has a hepatotoxic metabolite.
|
|
|
Hepatotoxic definition
|
chemical-driven liver damage. It is a possible side-effect of certain medications
|
|
|
Excretion
|
Renal, billiary, fecal, breast milk, lungs, saliva, sweat
|
|
|
Renal Excretion
|
glomerular filtration, proximal tubule secretion, distal tubular secretion, renal excretion
|
|
|
Plasma Drug Levels
|
there is a direct relationship between therapeutic and toxic responses and the amount of drug present in plasma
|
|
|
MEC
|
Minimum effective concentration
|
|
|
MEC definition
|
the plasma drug level below which therapeutic effects will not occur
|
|
|
Toxic Concentration
|
the plasma drug level at which toxic effects occur
|
|
|
Therapeutic Window
|
the range of plama drug levels falling between the MEC and the toxic concentration. Drugs with narrow range of therapeutic window are more apt to cause toxicity. Digoxin is the classic example
|
|
|
Drug Half life
|
the time required for the amount of drug in the body to decrease(eliminated) by 50%. Drugs with a short half-life but a long dosing interval will lose the MEC
|
|
|
Plateau
|
when the amount of drug eliminated between doses equals the dose administered. Average drug levels will remain constant and plateau will have been reached.
|
|
|
Techniques for reducing fluctuations in plasma drug levels
|
Continuous infusion (plasma levels kept constant), constant daily dose reduce size and interval of dosage.
|
|
|
Loading Dose
|
Large initial dose which achieve plateau rapidly
|
|
|
Maintenance Dose
|
small doses to maintain plateau
|
|
|
Pharmacodynamics
|
the study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced. In short, what the drug does to the body.
|
|
|
Dose Response Relationship
|
Graded relationships. As the dosage increases the response becomes greater
|
|
|
Maximal Efficacy
|
the largest effect a drug can produce
|
|
|
Potency
|
the amount of drug that must be given to elicit a response
|
|
|
Drug Receptor
|
any functional macromolecule in a cell to which a drug binds to produce its effect
|
|
|
Receptor Compatibility
|
the ability of a drug to bind to it's receptor depends on the size and shape of the drug and it’s receptor, a single receptor can be responsible for regulating several physiologic activities. Drugs mimic or block the actions of the body's own regulatory mechanisms.
|
|
|
Intrinsic Activity
|
the ability of a drug to activate a receptor following binding and is linked to efficacy.
|
|
