Lecture 2 - Drug target interactions and clinical effects Flashcards
describe pharmacokinetics vs pharmacodynamics
pharmacokinetics is what the body does to the drugs - ADME
pharmacodynamics is the effect of the drug on the body - targets
describe absorption of the body on the drug.
drugs characteristics that affect drug absorption
- molecular weight, ionisation, solubility, and formulation
- liberation (pharmacology)
factors that affect drug absorption related to the patient
- gastric pH, route of administration and contents of the GI tract
treatment
- onset of acute
- acute symptoms vs chronic condition
dosage regime
- solubility and elimination
describe distribution of a drug in the body
membrane permeability
- cross the membrane to the site of action
protein plasma binding
- bound drugs cannot cross the membrane
- malnutrition = decreased albumin which increases free drug
Lipohilicity of the drug
- lipophilic rugs accumulate in adipose tissue
- volume of distribution: large volume of distribution = extensive in tissues
Describe digoxin and its distribution in the body
digoxin in a Na-K ATPase inhibitor
it is a cardiac glycosides (used to treat heart failure and irregular heartbeat)
70 to 80% of oral dose is absorbed
half-life is 26-45 hours
digoxin is extensively distributed in tissues which is reflected by its large volume of distribution
describe metabolism of a drug in body
liver - the main routeof drug metabolism
the liver can also be used to convert pro-drug(inactive) to an active state
two types of reactions
- Phase I (cytochrome p450)
-Phase II
describe statins and their metabolism in the body
some are prodrugs
CYP3A4 metabolism
grapefruit interactions with warfarin/ coumarins
interactions with certain antimycotics
describe ADME or PK considerations
steady state: drug that is administered is equal to the amount of drug eliminated in one dosing interval resulting in a plate or constant serum drug levels
drugs with a shorter half life reach steady state faster. drugs with a long half life can take days to weeks to reach steady state
loading dose: allows rapid achievement of therapeutic serum levels
describe enzyme kinetics
follows linear kinetics until enzymes become saturated
enzymes that are responsible for metabolism/ elimination become saturated resulting in a non-proportional increase in drug levels
describe the pharmacodynamics: efficacy and potency
efficacy is the degree to which a drug is able to produce the desired effect
potency is the amount of drug required to produce 50% of the maximal response the drug is capable of inducing
- used to compare compounds within classes of drugs
describe the other pharmacodynamics
effective concentration 50% - this is the concentration that specifically induced for a clinical response in 50% of subjects
lethal dose 50% - this is the concentration of drug which causes death in 50% of subjects
therapeutic index - this is a measure of the safety of the drug - LD50 / ED50
margin - this is the margin between the therapeutic effect and the lethal doses of a drug
what do most drugs bind to?
most drugs bind to cellular receptors
- a ligand that binds and activates a receptor is an agonist
neurotransmitters and hormones are endogenous ligands
drugs are exogenous
pharmacological effects are due to alteration of an intrinsic physiological pathway and not the creation of a new process
- with side effects
how do other drugs work?
some drugs work without any direct innervation within the cell
example: mannitol interferes osmotically with water reabsorption by the kidneys
what are cell surface receptors?
proteins and glycoproteins
- found in the cell surface, on an organelle within the cell or in the cytoplasm
finite number of receptors in a given cell
- receptor mediate responses upon saturation of all receptors
what are drug receptors?
action occur when a drug binds to a receptor and the action may be:
- ion channel open or closes
- second messenger is activated
cAMP, cGMP, inositol phosphate and ca2+
initiates a series of chemical reactions
- cellular functions can be ‘turned off’ or ‘turned on’
what types of drugs causes contraction?
agonists
- noradrenaline
histamine
angiotensin
calcium Channel blockers
