Receptor Theory, Signal Transduction, And Dose-Response Flashcards
Drugs
. Small organic molecules that have specific 3D shape and electronic charge configuration
. Interact w/ macromolecules that have complementary configurations (receptors)
Examples of drug receptors
. NT and hormone receptors . Enzymes . Transport proteins . Ion channels . Ion receptors . Cell recognition and adhesion molecules . Nuclei acids
For most drugs, the duration of action is directly related to ______
. Time in which drug is bound to receptor
. When drug is cleared from bloodstream it dissociates from receptor and it’s action ends
Examples of drugs that do not act at specific receptors
. Antacids
. Cheating agents
Forces involved in drug-receptor interactions
. Electrostatic interactions (btw functional groups w/ opposite charges
. Hydrophobic ( non polar regions of drug and receptor interact)
. Van der waals
. Covalent bonding (drugs bind irreversibly w. Receptor through covalent binding)
Types of Electrostatic interactions
. Ionic: fully charged
. Dipolar: partially charged
. H bonding
Drug-receptor interactions have a high degree of ____ specificity
. Structural
. Slight changes in structure of drug causes large changes in activity
Agonism
. Drugs interact w/ receptors that activate receptor-effector mechanism (signal transduction pathways) and alter function of target cell
Competitive antagonism
. Drug occupies receptor and prevents agonist from binding to receptor
. Need more conc. Of agonist in order to reach same intensity of response
Affinity
. Propensity of drug to bind to given receptor
Intrinsic activity
. Ability of drug to initiate a response by producing conformational changes needed to activate receptor-effector mechanism
. Agonist has both ___ and _____ drug-receptor interactions
. it has affinity and intrinsic activity
Does a competitive antagonist have affinity or intrinsic activity?
. It has affinity
. Has no intrinsic activity
Other types of actions besides competitive antagonism
. Partial agonists
. Mixed agonist/antagonists
. Inverse agonists
Inverse agonists
. Drugs that can bind to receptor and stabilize the receptor in an inactive state
. Results in effects on the signaling pathway that are opposite those of an agonist
. Drug decreases basal activity of signaling response mechanism
Non-competitive antagonism
. Antagonist on the same molecule but at different binding site than antagonist
. Never get to same intensity of response as agonist alone
Chemical antagonism
. Antagonist interacts directly with agonist drug an inactivates it
Functional antagonism
. Antagonist acts through a completely different mechanism to counteract the effects of the agonist
Concentration-effect relationships
. Intensity of drug effect is dependent on drug conc. At site of action
General process and assumptions of concentration-effect relationships
. Relationship is reversible, equilibrium process
. One drug molecule combines w. One receptor
. Response is directly related to number of receptors occupies
. Amount of drug actually bound is negligible compared to the amount free
Equation to determine concentration of drug to get certain intensity of drug’s effect
. Effect = Max effect [D]/(Kd + [D])
. [D] is free drug conc.
. KD is dissociation constant and represents drug conc. At which effect is 1/2 of the max
Drug-receptor interactions follow principles described for ___ interactions
. Enzyme-substrate
Michealis Menten equation
V = Vmax[S]/(Km+[S])
Drug potency
. Amount of drug needed to produce given effect
Efficacy
. Ability of drug to product an effect w/o regard to concentration
Graded dose response relationship
. Shows intensity of a drug effect in a subject is a function of the drug dose
. Has biological variation
. Potently is the position of the curve on X axis determined by pharmacokinetics and inherent ability fo drug to bind to receptor and product effect
. Threshold dose
. Any dose below that amount no effect would be seen
Maximal effect (efficacy)
. Determined by pharmacokinetics of drug and inherent ability to produce an egg etc
Quantal dose-response relationship
. Shows the percent of subjects in a population that exhibit a response of given intensity as a function of a drug dose
. Curves can be used to compare effect of different drugs in population os test subjects
. Useful to compare dose of single drug that produces different effects in a population of subsections
Therapeutic index
LD50/ED50
. LD50: lethal dose. Where 50% of subjects died
. ED50: 50% of subjects reached efficacy in response of drug
Toxicity index
. TI = TD50/ED50
. TD50: dose amount where 50% of subjects felt toxic effect
. TD50: dose amount where 50% of subject felt efficacy response
Tolerance
. Dec. sensitivty to drug
. Seen after chronic treatment
Pharmacokinetic tolerance
. Due to induction of enzymes that metabolize drug
Pharmacodynamic tolerance
. Due to changes in sensitivity of drug receptors
. Usually involves compensatory changes in number of receptors or sensitivity of receptors (effector mechanisms)
Tachyphylaxis
. Rapidly developing pharmacodynamic tolerance
Physical drug dependence
. Tolerance
. Withdrawal syndrome ( physiologic symptoms that appear when drug is abruptly stopped, effects opposite of effect drug produces)
Pharmacodynamic basis of tolerance and dependence
. Related to compensatory changes in receptors and effector mechanism
Idiosyncratic effect
Unusual drug effect in certain individuals
Drug allergy
. Drug acts as allergen to activate immune response
Additive effects
. Combined drug effect is equal to sum of effects of each drug
Synergistic effect
. Combined drug effect of 2 drugs is greater than sum of the effects of each drug alone
Potentiation
. 1 drug enhances the toxic actions of another
