Pharmacology Flashcards
pharmacodynamics
what a drug does to the body
pharmacokinetics
what the body does to a drug
what is selectivity?
the ability of a drug to distinguish between different molecular targets within the body
what do targets generally include?
targets that are unique to invaders and are not on eukaryotic human cells
what regulatory proteins do drugs bind to to modify their function?
enzymes, carrier molecules, ion channels, receptors
what does an agonist do
binds to a receptor to produce a cellular response
what does an antagonist do?
a drug that reduces or blocks the actions of an agonist by binding to the same receptor
what is selectivity dependant on?
the dose of a drug
what are receptors made of?
protein, or glycoprotein, macromoles
what are ligand-gated ion channels targeted by?
hydrophilic signalling molecules (fast neurotransmitters such as acetyl choline)
what are G protein-coupled receptors also know as?
metabotropic receptors
what are G protein-coupled receptors targeted by?
hydrophilic signal molecules (slow neurotransmitters such as acetyl choline, amino acids, peptide hormones)
what forms ion channels?
glycoproteins
what can ion channels be gated by?
chemical signals (ligand-gated), transmembrane voltage (voltage-gated) and physical stimuli (thermal and mechanical energy)
classic example of ligand-gated ion channels?
the nicotinic acetylcholine receptor of skeletal muscle and neurones
what does the nicotinic acetylcholine receptor look like?
consists of separate glycoprotein subunits that form a central ion conducting channel
most cell surface receptors signal via what?
second messenger systems
structure of G protein-coupled receptors? chemical
single polypeptide with extracellular NH2 and intracellular COOH termini
what does the G protein-coupled receptor contain?
seven transmembrane a-helical spans joined by 3 intracellular loops
what type of protein is a G protein? think location
peripheral membrane protein
what does a G protein consist of?
3 polypeptide subunits (alpha, beta and gamma)
what binding site does the G protein have and what does it allow?
a guanine nucleotide binding site in the alpha subunit that can hold guanine triphosphate or guanine diphosphate
how are G proteins activated?
they are activated via agonist binding to the GPCR to which they preferentially couple
what occupies the guanine nucleotide binding side in the non-active state of the G protein?
GDP
what occupies the guanine nucleotide binding side in the active state of the G protein?
GTP. The alpha and beta subunits dissociate from each other
what does the activation of the GPCR activate?
A G protein
example of signalling that uses receptor kinases
insulin sigalling
example of signalling that uses ligand-gated transcription factors
nuclear receptors and steroid hormones
what is drug metabolism?
drug transformation by metabolism by the liver and other tissues
what can drugs be excreted by?
in urine, faeces or bile
what is bulk flow?
the movement of drugs around the body via the circulatory system
what type of drugs are more likely to diffuse across the lipid bilayer?
lipid soluble drugs
what are aqueous pores formed by?
aquaporin
what type of drugs cross the cell membrane via passive diffusion?
lipid soluble drugs
how do small molecules cross the cell membrane by facilitated diffusion?
via specialised carrier proteins. The binding of the drug on the protein causes a conformational change which allows the drug to diffuse across the membrane
how do small molecules travel with active transport
via specialised carrier proteins
what does saturation kinetics mean?
any process that has a limiting factor (limited number of specialised carrier)
what are the principle sites of carrier mediated drug transport? (facilitated dissuion and active transport) 5
blood brain barrier, gastrointestinal tract, placenta, renal tubule and binary tract
what type of drug is endocytosis used for?
transporting large drugs across the cell membrane (vitamin B12)
what is the pKa?
the pH at which 50% of the drug is ionised and 50% of the drug is un-ionised
can the non-ionised form of a drug permeate the membrane?
for many drugs, yes
what compartments do weak bases accumulate in?
compartments with low pH
what compartments do weak acids accumulate in?
compartments with high pH
what type of pH do weak acids need to be absorbed?
low pH
what type of pH do weak acids need to be absorbed?
high pH
where does most oral drug absorption occur?
in the small intestine due to the large surface area
what is the apparent volume of distribution? Vd
The extent to which a drug partitions between the plasma and tissue compartments
what is the equation for volume of distribution?
Vd = Dose/ [drug]plasma
what type of drugs find it more difficult to cross membranes and what does this do to the Vd?
hydrophilic and ionised drugs, Vd is closer to total body volume of water (41L)
what type of drugs easily cross membranes and what does this do to the Vd?
lipophilic drugs. Vd is generally greater than total body volume (41L)
what does a large Ka mean?
acid is strong
what is the most abundant plasma protein?
albumin
what is the effect of plasma protein binding on drug affinity?
it reduces the availability of the drug for diffusion to the drug target organ
define drug metabolism ?
enzymatic conversion of the drug to another chemical entity
what is the most important drug metabolising organ
the liver
but also the kidney, gut mucosa, lungs and skin
when administered by the enteral (oral) route, metabolism in the liver…
REDUCES THE BIOAVAILABILITY OF DRUGS
what is the bioavailability of the drug?
the systemic circulation of drug that is available
where do the two phases of drug metabolism happen?
primarily in the liver
where are hepatic drug-metabolising enzymes found?
embedded in the smooth endoplasmic reticulum of liver hepatocyes
what changes in the drug can happen in phase 1
oxidation (most common), reduction or hydrolysis
what do phase 1 metabolism reactions usually produce?
chemically reactive metabolites that can be pharmacologically active and or toxic
what happens when people lack P450 activity?
higher drug plasma levels (adverse reactions)
what happens when people have too much P450 activity?
lower drug plasma levels which reduces drug action
what happens during phase 2 metabolism reactions?
drug combines with one of several polar molecules to form a water-soluble metabolite that can be readily excreted via the kidney
what are the principal organs for drug elimination?
the kindneys, by renal filtration of blood plasma
during renal filtration, what is reabsorbed into blood circulation by renal tubules?
water and most electrolytes
what drug things are rendered polar by phase 2 metabolism and excreted in the urine?
drug metabolites that are not reabsorbed
what is clearance? (CL)
an expression for the elimination
