Basic Principles I Flashcards
pharmacology
-bio, biochem, phys, path, micro, psych, medicinal chem all go into pharmacology, which lead to pharmacodynamics, therapeutics and chemo, and tox (treatment of patients)
pharmacodynamics
-given meds, leading to a response
drug action
- molecular action
- invisible
drug effect
- pharmacologic effect
- visible response
selectivity
- property of drug to cause a specific effect
- few drugs produce a single effect
- primary effect is desired and second may or may not be
- can be one molecular action leading to multiple effects or two molecular action leading to combined effects
pharmacokinetic
-drug and elimination
pharmacodynamic
-how it works
-types of drug actions”
physiochemical and receptor interactions
physiochemical actions
- simple chemical interactions
- antacids
- antiseptics
- not very specific
receptor interactions
- interaction of drug with physiologic receptors-macromolecules
- most drugs
drug receptors
- drug receptor interactions cause molecular events to occur in each cell
- enough of these events cause a change in cell function
- ultimately results in change in tissue function
receptors
- macromolecules, particularly proteins
- may be on or in a cell or free in the plasma or extracellular fluid
- present as part of the normal biochemical and physiologic mechanisms and usually interact with endogenous compound
- function both as ligand binder and as an effector
- the natural ligand or a drug which resembles it can bind and modulate usual activity
- each receptor occupied might be stimulated or inhibited
- each cell in a tissue contains a large population of receptors that are easily accessible to drugs
receptors 2
- each drug receptor interaction produces a small change in the biochemical or electrochemical homeostasis of the cell
- cumulative effects of many drug receptor interactions will lead to a change in the function of the cell and then the tissue
- when enough cells in a tissue are affected then the function of the tissue is altered and an observable pharmacologic response can be noted
- maximal response is eventually reached which is related to the number of drug receptor interactions and the physiologic capacity of the tissue
types of receptors
- membrane bound-neural synapse, ion channels
- enzymes-intracellular or extra
- structural macromolecules- MT
- intracellular macro- steroid receptors, RNA
- cell membrane itself- change electrical potential, fluidity
as subunit
-increases adenylyl cyclase and Ca currents
ai subunit
-decreases adenylyl cyclase and increases K currents
ao subinit
-decrease Ca currents
aq subunits
-increases phospholipase CB
a13 subunit
-increase Na/H exchange
at subunit
-increases cCMP-phosphodiesterase (vision)
aolf subunit
-increase adenylyl cyclase (olfaction)
drug receptor bonds
- reversible are ionic, van der waals, hydrogen
- irreversible is covalent
receptor amp and transduction
- aB together
- GDP off, interaction with receptor and ligand, GTP binds
- subunits split
- action
- GTPase on A gets rid of GTP
- back together
G proteins
- regulate the activity of:
- distinct effector proteins in the cell- enzymes, channels, transport proteins
- can be multiple G proteins in a single cell
- act as switches that are turned on by the receptor and turn themselves off in a few seconds
- several drugs can stimulate different receptors but ultimately influence the same effector protein through the mediation of a G protein that is shared by different receptors
- stimulus averaging or modulation can be achieved
second messenger
- also produce amplification of the drug receptor interaction
- converts an even that happens outside the cell into a change that happens inside the cell
- some second messengers can cause different effects in different tissues
- changing the biochemical balance of substrates in metabolic pathways and activating or deactivating enzyme systems can have a profound effects on the function of the cells in a tissue