Minimum effective concentration 

plasma drug level below which therapeutic effects will not occur

Toxic concentration

Plasma drug levels climb to high, where toxic effects begin

Therapeutic range (objective of drug dosing is to be here)

Half-life

• Time for the amt of drug in the body to decrease by 50% (after 2 1/2 lifes 25% left)
• Determines the frequency of drug administration
• Influenced by liver and renal function 

Steady state/Plateau concentration (how a loading dose would impact this concept)

• Administering a drug repeatedly will build up the drug until a plateau is achieved
• When amt of drug eliminated = dose administered, plateau will be reached
• If administered repeatedly, plateau will be reached in ~4 half lives
• When drug discontinued 94% of drug is eliminated in ~ 4 half lives
• Highest = peak | level = trough (must be kept above MEC), to reduce flucuation…
  • Continuous infusion
  • Depot preperation
  • Reduce both size of each dose and dosing interveal

Single-dose time curve

Drug level rise during absorption, then decline as drug is metabolized, and is finally excreted. There is a latency period between drug admin and onset of effects, this period is determined by rate of absorption. No clear delineation between MEAD

Loading dose

If drug has a long ½ life (steady state may take weeks), if plateau is required sooner than you may give a loading dose (large initial dose). After loading dose, plateau may be maintained by smaller doses (maintainence doses)            

Receptors

where are they located;

how are they named

dynamic properties; specificity

•RECEPTORS:  specific macromolecules located on the surface (usually) OR inside cell

receptor name based on type of drug it interacts with ( ie adnergic receptor) each cell may have thousands of them

receptors are highly specific to a molc and control only a few processes

because receptors have this specificity, we can make a drug to interact with only that receptor. Although drug is selective for one drug, the receptor may control various processes, and effects maybe widespread

When a drug binds, it mimics or blocks the actions of endogenous regulatory molecules, thus altering the physiologic activity that receptor controls

  In general:  the 4 receptor families

ü  Cell membrane- embedded Enzymes –

o   Binding of regulatory molc or drug increase embedded enzyme catalytic activity

ü  Ligand Gated ion Channels –

o   Binding of regulator molc or drug channel opens, allowing inward/outward flow

ü  G-Protein Coupled Receptor Systems (within the cell membrane)

o   3 parts: Receptor, G protein, Effector

o   binding of regulator molc or drug activates the receptor which actvates G protein, which activates the effector(s)

ü  Transcription Factors (within the cell)

o   Responses to this factor is DELAYED. Binding of regulatory molc or drug stimulates the transcripition of mRNA (can only be activated by drugs sufficiently lipid soluable)

  Affinity 

 molecules that activate receptors (endogenous local mediator molc or drugs)

o   Not all drugs are agonsits

ü  Interact w/ receptor but do not cause a response “place holder”

o   Designed to counteract the effect of endogenous substances or another drug

o   If there is no agonist present, admin of antagonist will have no observable effect

ü  Dose of a drug needed to produce the same response another drug elicited 

Clinical Implications of Efficacy

What is ED₅₀

What is LD₅₀

Is it better ot have a smaller or larger theraputic index (LD₅₀/ED₅₀)?

ü  ED₅₀   dose required to produce a defined therapeutic response in 50% of the ppln

ü  LD₅₀ Dose that is lethal to 50% of animals treated    

ü  Therapeutic index = (LD₅₀/ ED₅₀) 

smaller # = unsafer | larger # = safer

Simple occupancy theory     

ü  Intensity of response to a drug is proportion to # of receptors occupied by that drug

ü  Max response will occur when all available receptors have been occupied

ü  Dose not take into account 1) ability to bind 2) ability to elicit a response

ü  Does not explain efficacy or potency

modified occupancy theory 

  Factors in 1) affinity and 2) intrinsic activity (ability to activate upon binding)

ü  bind reversibly, competitive antagonist produce receptor blockate by competing with agonists for receptor binding. If agonist and antagonist have equal binding affinity the one in higher concentration will occupy the receptor. Because of this inhibition they cause is SURMOUNTBALE

o   Example:  ED₅₀ = normally 10 mg; with antagonist ED₅₀ =50mg

ü  bind irreversibly to receptors (resulting in  a reduction total # of receptors available for activation by an agonist). B/c they reduce total # of recetpors available for activation the reduce MAXIMAL RESPONSE. No matter how much agonist is added MAXIMAL response cannot be achieved. Noncompetitive antagonists wear off as the receptors to which they are bound are replaced

Synergism 

when the combined effects of 2 drugs acting simultaneously are greater than the algebraic sum of the individual effects of these drugs, the drugs are acting synergistically