Pharmacodynamics Flashcards
What is pharmacodynamics?
Study of action of drugs on the body
What is pharmacokinetics?
Study of what the body does to the drug
What is the generic name of a drug?
Non-proprietary name that each chemical can be given
What is the trade name of a drug?
Proprietary name, owned by company
Targets of drug action
Proteins, DNA, lipids
What do inotropic receptors do?
Facilitate movement of ions across membranes
Require ligand binding - transient interaction
Characteristics of ionotropic receptors
- Require ligand binding - transient interaction (binding and dissociation happens rapidly)
- Hyperpolarization or depolarization of cell
- Typically penatameric
- Pore in centre allows ions to flow
- Signalling time is very fast - milliseconds
Characteristics of G-protein coupled receptors
- Largest family
- Metabotropic receptors
- 7 transmembrane domains
- N-terminal domain is where drug binds
- C terminal where G protein signaling takes place
- Activating protein can influence ion channel activity or activate second messenger cascade
- Ion channel excitability
- G alpha s and G alpha I act via same secondary messenger
- AC = adenylate cyclase, which catalyses of ATP to cAMP which influences PKA
- G alpha I inhibits adenylate cyclase - negative effect cAMP and PKA
- G alpha q activates phospholipase C which catalyses PIP2 to DAG and IP3
- DAG and IP3 influence PKC
- IP3 is calcium regulator
How do kinase linked receptors work?
- Single membrane spanning domain
- Dimerization when drug binds
- When drug binds, autophosphorylation of tyrosine kinase domain
- Dimerization attracts intercellular proteins to express SH2 domain to activate targets, most common target is Ras/Raf/MAPK or Jak/Stat pathway
Characteristics of nuclear receptors
- Nuclear or cytosolic
- Ligands lipid soluble
- Act as transcription factors
- Take hours
- e.g. oestrogen receptor
- Mainly steroids or hormones
- Receptor activated when ligand binds
- Nuclear receptors can increase or decrease gene expression
What is drug specificity?
Binds selectively to particular receptor types
What do agonists do?
Activate receptors
What do antagonists do?
Block receptors, often inhibit endogenous agonist action
What is the binding affinity?
How well does the drug bind to the receptor
What is efficacy?
Ability of drug to bring about full response
What is a full agonist?
Elicit 100% of endogenous agonist
What is a partial agonist?
Elicits <100% effect
What is a super agonist?
> 100% of endogenous effect
What is an inverse agonist?
Reduce basal receptor activity
What is potency?
Agonist drug potency is a product of affinity and efficacy
What is an equipotent molar ratio?
Picking a threshold and observing concentration required to get that response
Why don’t antagonists activate receptors?
They have zero efficacy
What are receptor antagonists?
Reversible or irreversible - competitive (reversible) but can be competitive or uncompetitive
What are non-receptor antagonists?
Chemical, physiological (produce opposite effect of agonist, e.g. insulin and glucagon) and pharmacokinetic (influencing action of one drug by modifying its pharmacokinetic profile)
