PHRM20001 - Common concepts/terms

Agonist

Ligand that activates a receptor

Antagonist

Ligand that binds to a receptor without activity

Protein Drug Targets (RICE)

Receptors, Ion channels, Carriers, Enzymes

Pharmacodynamics

Pharmacological principles that describe drug effects on the body, explaining

Affinity 

Likelihood of the ligand to bind to its receptor

Efficacy

Likelihood of a bound ligand to activate a receptor

E_max

Maximum response/effect that drug can produce

Potency

Drug concentration required to elicit a given effect

Intrinsic efficacy

Drug-dependent component of efficacy

Reversible competitive antagonists

Drugs that binds to the orthosteric site without activating the receptor AND can dissociate & rebind continuously (e.g. Naloxone)

K_B

Equilibrium dissociation constant of competitive antagonists

IC₅₀

Concentration of antagonist required to reduce a response to a fixed concentration of agonist by 50%

Irreversible competitive antagonists

Drugs that bind covalently to orthosteric site OR dissociate very slowly from site. At high concentrations, they CANNOT be out-competed (e.g. phenoxybenzamine)

Partial agonists

Alters the response of an agonist with higher efficacy that binds to the same site, acting as a competitive, reversible antagonist.

Causes a rightward shift in response curve.

Chemical antagonist

Antagonising molecule that directly binds to or destroys the ligand

Functional antagonist

Opposes biological effects of an antagonist by acting at a different receptor (as an agonist)

What NS divisions is aceytlcholine the primary neurotransmitter

Somatic NS, Parasympathetic NS (& Ganglionic transmission)

What NS division is noradrenaline the primary neurotransmitter

Sympathetic NS

Sympathomimetics

Drugs that mimic the effects of the sympathetic nervous system (SNS)

Bioavailability

Proportion of active drug which enters systemic circulation. This is affected by:

• How much drug is absorbed

• How much drug undergoes 1st pass metabolism

Pharmacokinetics

The ADME of a drug

ADME

What determines dose - Absorption, Distribution, Metabolism, Elimination

Volume of distribution (Vd)

Volume of body water in which a drug appears to be dissolved in after is has dissolved & distributed throughout the body

Vd=(amount in body)/(plasma concentration) = (dose given)/(initial concentration)

Pharmacogenetics

Studies the variability in drug responses that relate to genetic differences

Pharmacogenomics

Utilisation of global genomic technologies (gene expression profiling/whole genome sequencing etc.) to serve pharmacogenetic aims 

Prodrug

Compound with little or no pharmacological activity that metabolizes inside the body and converts into a pharmacologically active drug compound

Clearance

Measure of the sum of the irreversible elimination process

Half-life

Constant time for [plasma] to fall by half independent of the starting concentration

t_1/2= (volume of distribution)/(clearance)

Half life determines

• duration of action after a single dose

• time to steady state with chronic dosing

  • usually ~6 half-lives

• frequency at which dose should be given

Biologics

Non-small molecule therapeutic originating from a biological source

Modality

Nature of therapeutic approach