Basic Principles of Pharmacology I Flashcards
0
Q
Drug effect
A
Pharmacologic effect= visible response
1
Q
Drug action
A
Molecular action= invisible
2
Q
Drug selectivity
A
- property of drug to cause a specific effect-few drugs produce a single effect
- primary effect= desired
- secondary effect- side effects- may or may not be desired
3
Q
Interactions of Drug Actions and Effects
A
- some drugs have a single major mechanism of action and this action produces multiple effects
- another drug may have several different actions either or both of which are responsible for a single effect and then have an additional action which causes a single effect
4
Q
Pharmacokinetics
A
- time course of drug absorption, actions and elimination
- has to deal with the systemic circulation what is bound and what is free and what is tissue bound
- and elimination
5
Q
Pharmacodynamics
A
- types of drug actions
- physiochemical actions- simple chemical interactions- ie antacids, antiseptics- not very specific
- receptor interactions- internation of drug with physiologic receptors-macromolecular most drugs
6
Q
Basic Sciences and Clinical Medicine of Pharm
A
- define the physiology of the target tissue: identify the receptors and the endogenous agonists that stimulate the tissue
- create drugs that mimic the endogenous agonists
- tests the drugs in the target tissues- laboratory and clinical trials
7
Q
Doses and weights
A
- doses are quantities measured by weight (mg, mcg)
- pharmacodynamic interactions and the pharmcokinetic events occur at the molecular level
- mg and molecules- mole 6.022 x 10^23
8
Q
Receptors
A
- Macromolecules, particularly proteins. May be on or in a cell or free in the plasma or extracellular fluid
- these are present as part of the normal biochemical and physiologic mechanisms and usually interact with endogenous compounds. They are specific
- they function both as ligand binder and as an effector
- the natural ligand (agnoist) or a drug which resembles it can bind a receptor and modulate its usual activity
- each receptor occupied might be stimulated (agonist) or inhibited (antagonist)
- each cell in a tissue contains a large population of receptors that are easily accessible to drugs
- each drug receptor interaction produces a small change in the biochemical or electrochemical homeostasis of the cell. The cumulative effects of many drug receptor interactions will lead to a change in the function of the cell
- when enough cells in a tissue are affected then the function of the tissue is altered and an observalbe pharmacologic response can be noted
- a maximal response is eventually achieved which is related to the number of drug receptor interactions and the physiologic capacity of the tissue (normal vs. diseased)
9
Q
Types of Receptors
A
- Membrane bound- eg. in neural synapse, ion channels
- enzymes- intracellular or extracellular
- structural macromolcules- eg microtubules
- intracellular macromolecules- eg steroid receptors, RNA
- cell membrane itself- change electrical potential fluidity
10
Q
Regulated by alpha subunits
A
- alpha s- increase adenylyl cyclase, increase Ca2+
- alpha i- decrease adenylyl cyclase, increase K+ currents
- alpha o- decrease Ca2+
- alpha q- increase phospholipase CB
- alpha 13- increase Na+/H+ exchange
- alpha t-increase cGMP-phosphodiesterase (vision)
- alphaolf- increase adenylyl cyclase (olfaction)
11
Q
Beta subunit regulation
A
- receptor-operated K+currents
- adenylyl cyclase
- phospholipase CB
12
Q
Reversible Bonds
A
- Ionic
- Van der Waals
- Hydrogen
13
Q
G proteins
A
- drug- receptor interations- fractions of seconds activate G protein activity that lasts for seconds
- G proteins (GTP binding proteins)- regulate the activity of
- distinct effector proteins in the cell- enzymes, channels, transport proteins
- there 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 the different receptors. Thus stimulus averaging or modulation can be achieved
14
Q
Second Messenger
A
- also produce amplification of the drug receptor interaction
- converts an event that happens outside the cell (ie receptor binding) into a change that happens inside the cell-some second messengers can cause different effects in different tissues
15
Q
Changing biochemical balance
A
- changing the biochemical balance of substrates in metabolic pathways and activating or deactivation enzyme systems can have profound effects on the function of the cells in a tissue
- eg cAMP, Ca2+ may be stimulated or inhibited by G proteins
16
Q
Structure-Activity Relationships
A
- the structure of the drug determines how it will fit into the receptor
- the better the fit, the better the stimulation
- subtle changes in structure amongst a class of drugs can greatly influence the drugs’ effects
- stereoisomers
17
Q
Quantitative Descriptions of Drug Action
A
- these are attempts to take experimental data, combine it with certain assumptions and make a model that works for most systems
- interaction at equilibrium: Drug (D)+ Receptor (R) -> Effect
18
Q
Dose response relationship
A
- how to measure and compare drug effects
- you have have dose response curve but also can change it to log dose relationship
- thresold- the beginning of the curve- dose of agonist at which a response begins. May related to the affinity of the agonist for the receptor
- slope-rate of rise of the response on the steep portion of the curve, Log of EC50 also relates to affinity
- maximal asymptote- the top of the curve represents E Max for that particular agonist
19
Q
Receptor Occupancy
A
- intensity of response is proportional to the fraction of the receptors occupied
- Effect = Emax [D] / Kd + [D] where Kd= EC 50
- like enzyme Michaelis-Menton- like enzyme but drug is not consumed as a substrate the macromolecule is one of the reactants and not simply a catalyst
20
Q
Intrinsic Activity
A
- ability to stimulate the receptor once bound
- relates to structure and influences efficacy and potency
- greater intrinsic activity= greater efficacy
21
Q
Spare Receptors
A
- not all receptors need to be occupied to achieve Emax
- less efficacious agonists may need to occupy more receptors than highly efficacious agonists
22
Q
Secondary Receptors
A
-outside of the target tissues, may mediate other effects of the drug side effects
23
Q
Receptor Regulation
A
- a cell can up or down regulate a population of receptors by changing the total number of receptors or their sensitivity
- homeostasis
- eg denervation hypersensitivity
- eg desensitization- can occur with down regulation of the receptor or with fatigue or depletion of the intracellular or tissue mechanisms
24
Q
Agonist Drugs
A
- these bind to the receptor and produce a pharmacologic effect
- two important events: bind to the receptor and activate receptor after binding
- better fit to the receptor from more specific structure of the molecule results in more DR and an effect at lower doses
- in classes of drugs there will be variation in intrinsic activity, based on differences in structure, that will influence the therapeutic effect and use of particular agents
- 3 different agonists- all able to achieve Emax but with different doses- they differ by binding but not in activating the receptor, all have the same intrinsic activity
- there can be agonists with different intrinsic activity but the same affinity- these agonists bind to receptor in the same way but differ in activating the receptor
- two agonists with different intrinsic activity and different affinity
25
Q
Efficacy
A
- the ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor
- depends on the structure of the drug
26
Q
Potency
A
- relates to the amount of drug that is needed for an effect
- depends upon: the biologic system: receptor density, efficiency of the stimulus-response mechanisms of the tissue
- interaction of the drug with the receptor- affinity and efficacy
27
Q
Antagonist Drugs
A
- many things are learned about the structure and function of receptors from the use of antagonists
- antagonists can block the binding of agonists and prevent the pharmacologic response
- therapeutic agents to slow the system down ie paralytic agents
28
Q
Competitive Antagonists
A
- antagonist effect can be overcome by increasing the dose of the agonist
- simple competitive antagonist- a simultaneous equilibrium exists for both the agonist and antagonist
- binding of antagonist to the receptor is a weak bond and easily reversed
29
Q
Noncompetitive Antagonists
A
- can’t be overcome by increasing doses of agonist
- receptor remain occupied by antagonist and not enough DR interactions occur to achieve Emax
- simple explanation of noncompetitive inhibition: binding of antagonist to receptor is a strong bond- such as covalent- and not easily reversed (proton pump inhibitors)
- the inhibitor can either change the effector or the binding site
30
Q
Noncompetitive Antagonist
A
- change the effector, does not change binding of drug to the ligand site
- antagonist alters the effector site
- even if the ligand binds to the receptor it cannot initiate the effect
- inhibitor inactivates the effector
-also changes the binding site for the agonist by directly binding to it or by attaching to a different portion of the receptor and altering the agonist binding site
