N116 Unit 2 Pharmacodynamics

-Refers to what the drug does to the body to create a response
-Related to the mechanism of action of a drug
-Related to how a drug interacts with a target tissue
-Most drugs have specific effects as a result of binding to specific targets

individuals have different responses to drugs (therapeutic response)

median effective dose
-dose at which 50% of a population exhibited desired therapeutic response
-ED50 may be toxic for some patients and may not produce a meaningful response in others
-critical to monitor patient response to assess if dosage adjustment is indicated

median toxic dose
-Dose at which 50% of test subjects exhibit a response indicative of toxicity
-Usually determined in phase 1 studies

median lethal dose
-Dose at which 50% of test subjects are killed by drug
-Usually determined in pre-clinical (non-human) studies

ratio of LD50 to ED 50
TI = LD50 / ED50

it is considered to be safer than a drug with smaller TI

Describes relationship between dose of drug and intensity of drug response

-occurs at low doses; very little change in response as dose increases
-Few receptors or enzymes affected, therefore response is minimal

-linear phase; sharp increase in response as dose is increased
-As more receptors or enzymes are affected, intensity of response increases

-plateau phase; no change in response as dose increases
-Drug is bound to all receptors or enzymes, or symptoms have been alleviated. Increasing dose has no further effect

best range of doses to achieve a safe, therapeutic effect

-More receptors being affected by drug
-More enzymes being affected by response
-Patient symptoms affected by drug

-Amount of drug required to produce a particular intensity of response
-drug that requires lowest dose to produce particular intensity of response is most potent

-Maximum intensity of response produced by a particular dose of drug
-Drug with greatest intensity of response has highest efficacy

bind directly to/in bacteria/viruses

bind to DNA

protein structures
-'receptors' on surface of cell membranes
-specific (chemical structure = lock-key)
-binds endogenous substances (hormones, NT, etc.)
-drugs need to match the existing target receptor binding site

a change within cell OR blocks the receptor

strength of binding, length of binding

minimize interactions between "unlike" AAs and to maximize interactions between "like" AAs

receptor, enzymes, transporters, ion channels

Proteins can be communication strategies that allow communication between the outside of a cell and the inside of a cell

Proteins can act as catalysts in chemical reactions

Proteins can act as carriers, to pump ions or larger molecules in and out of cells

Quaternary proteins can form pores and control the transfer of charged ions

-Saturability: finite number, differs across body regions & types of tissues
-Relative Specificity & Competition (represented by affinity)
-Reversibility: not a covalent bond

A specific cellular activity is either enhanced or inhibited

the body's own agonist

-Noradrenaline binds to an adrenergic receptor (protein) on a vascular smooth muscle cell wall
-Noradrenaline acts as an agonist at this adrenergic receptor
-Binding of noradrenaline causes the smooth muscle cell to contract
-biological effect would be constriction of a blood vessel

Binds to receptor, mimics the action of endogenous substances; response may be greater than endogenous activity.

-Binds to receptor, produces weaker responses than endogenous substances
-the maximum response is smaller than that of a primary agonist even if all receptors occupied!

-Binds to receptor, prevent action of endogenous substances, usually by competing for receptor binding sites
-Antagonists do not usually have intrinsic activity

-Binds to the same site on the receptor as does the endogenous ligand
-Activates the receptor, causing the cell to respond as it would if the endogenous ligand was bound instead

-They reduce or antagonise the effects of the endogenous ligand
-Not the same as having no effect in the body
-Like agonists, these drugs bind to the same site as the endogenous ligand. Once bound, they do not produce a biological effect (they do not activate the receptor)
-Because they are bound to the binding site, they prevent an endogenous ligand binding to the site and activating the receptor

"blockers"
-block endogenous ligands for desired effect (e.g. lower blood pressure)

drug that plugs an ion channel (calcium channel blockers and anesthetics)

ability to initiate a response as a result of binding

affinity and efficacy

only affinity