M1 Lecture 1: General Pharm Flashcards
what does “pharmakon” mean in greek
medicine (drug)
what does “logos” mean in greek
study
what is a drug
any substance received by a biological system that is not for nutrition purposes (chemicals, biologicals, herbals)
pharmacodynamics
effects of drug on body (ex: to lower blood sugar, or blood pressure)
pharmacokinetics
effects on body on drug (absorption, distribution, metabolism, excretion [ADME])
pharmacogenomics
genetic factor that underlie variation of drug response (some ppl break down drugs faster/slower depending on the drug)
2 mechanisms of drug action and what does each do
- Mediated by receptors (most drugs): modulate an endogenous process (block cholesterol synthesis), stim or inhibit receptor (opioids - beta blockers)
- Not mediated by receptors (only few drugs)
what is a receptor
protein molecules, target for drug interactions
diff tissues will have a diff combination of receptors
both extra and intracellular receptors
extracellular receptors
location: outer surface of cell membrane
water soluble drugs*
intracellular receptors
location: inner surface of membrane inside cell, and within the cytoplasm or the nucleus
fat soluble drugs*
4 types of drug receptors
regulatory proteins, transporters, enzymes, structural proteins
regulatory proteins
“switch”
Regulates DNA transcription via expression of RNA polymerase
best described receptors
activated by endogenous ligands (hormones or neurotransmitters)
drug ex: propranolol - beta blocker
transporters
“gatekeeper”
Transports substances across cell membranes
- proteins that transport endogenous (electrolytes and irons) substances across cell membranes
- drugs often inhibit the function of the transporter
drug ex: SSRIs - antidepressants
enzymes
“overseer”
Increases rate of biological reactions
- proteins that catalyze a bio reaction
- drugs often inhibit the catalytic function of the enzyme
drug ex: statins - antineoplastic
structural proteins
“skeleton”
Contributes to cell’s structure
- proteins that contribute to the cell structure
- drugs that bind to structural proteins in the cell and disrupt their normal function
drugs ex: vincristine - antineoplastic
Drug-Receptor Interactions (D-R interactions)
- drugs acting on active sites: agonists/antagonists
Direct action on binding site
Agonist (full, partial, or inverse): produces intended response
Antagonist (reversible or irreversible): produces no response - drugs acting on allosteric sites: act on non-active sites, cause confrontational changes on the receptor
Action on alternative sites of receptor
Activator: promotes agonistic effect
Inhibitor: prevents agonistic effect without binding to active site
Full Agonists
Agonist boosts the effect: might be strong enough to fully use effect (full agonist is max effect)
Partial Agonist
Partial agonist is slight boost
Neutral Agonist
Neutral agonist (substance blocks effect but shows nothing)
Inverse Agonist
Inverse agonist (opposite effect as agonist)
Allosteric Activators
Activator: promotes agonistic effect
Potentiates the agonistic effect
(look at diagram on slide)
Active site is where a substrate would be, allosteric site is area might be affected by drug
Allosteric activator gets in contact with the allosteric site and changes it so the substance cannot bind with the changed active site
Allosteric Inhibitors
Non-competitive Inhibition
prevents agonistic effect without binding to active site
what are 4 receptors drugs are coupled with?
- intracellular receptors (ex: steroid receptors)
- enzyme-linked receptors (ex: insulin receptors)
- ion channel receptors (ex: calcium channel blockers receptors)
- g-protein coupled receptors (ex: adrenergic receptors)
what does D-R coupling trigger
a series of events (=signalling pathways)
modulates endogenous homeostasis or function
5 steps of D-R coupling and signalling mechanisms
- intracellular: Signal crosses plasma membrane to act on receptor in cell
- enzyme-linked: Signal binds to extracellular component of transmembrane protein to active enzyme activity. Signal binds to extracellular component of transmembrane protein, which is bound to tyrosine kinase enzyme intracellularly for activation
- ion-channel: Signal binds, which opens ion channel
- g-protein: Signal binds cell-surface receptor linked to effector enzyme on G-protein
dose
measured quantity of therapeutic agent taken at one time
drug response
pharmacodynamics response to drug
drug-response relationship
more drug given, greater the response until a certain point
lots of receptors - strong drug response
few receptors - weak response
no receptors - no response
diff receptors - no response
potency
dose required to produce response to a certain magnitude
efficacy
maximal response that a drug can produce as we increase dose
Therapeutic Index (TI)
quantitative measurement of relative safety of drug
- comparison of amount of drug that causes the therapeutic effect to the amount that causes toxicity
Higher TI = safer drug and vice versa
how to calculate therapeutic index
TI = TD50 (toxic dose to 50% of subjects) / ED50 (Effective dose in 50% of subjects)
its a ratio look at slide if need help
therapeutic range
range where drug has desired effects on body
drugs administered for therapeutic effect, not to cause adverse effects
drugs with narrow therapeutic range require closer monitoring (larger range = safer)
