pharmacodynamics Flashcards
drug interaction
1 + 1 = 2
Response elicited by combined drugs is equal to the combined response of the individual drugs
Sedative(chlorpheniramine maleate found in decongestants like Neozep + ethanol)
- ADDITIVE
drug interaction
1 + 1 = 3
Response elicited by combined drugs is greater than the combined responses of each individual
Penicillin G (antibiotic) removes the cell wall of the organism
Gentamicin (aminoglycoside antibiotic) inhibits protein synthesis in the organism
- SYNERGISTIC
drug interaction
0 + 1 = 2
Drug which has no effect enhances the effect of the second drug
Cimetidine + heparin (anticoagulant
(Cimetidine enhances the anticoagulation)
- POTENTIATION
drug interaction
1 + 1 = 0
Drug inhibits the effect of another drug
Heparin + protamine
- ANTAGONISM
study of detailed mechanism of action by which drug produce their pharmacologic effects
-provides a scientific basis for the selection and use of drugs
PHARMACODYNAMICS –
– specific cell molecules by which drugs interact to produce their effects
- most ligands (drugs or neurotransmitters) bind to protein molecules
- Determine the quantitative relations between dose or concentration of drug and pharmacologic effects
RECEPTORS
– largest family of receptors for pharmaceutical agents
G protein-coupled receptors (GPCRs)
CLASSIFICATION OF RECEPTORS
- Best characterized drug receptors
- Mediates the action of endogenous chemical signals like neurotransmitters, autacoids and hormones
- Mediates the effects of the most useful therapeutic agents
- REGULATORY PROTEIN
CLASSIFICATION OF RECEPTORS
- Inhibited (or less commonly, activated) by binding a drug
- Eg, dihydrofolate reductase, the receptor for methotrexate
- ENZYMES
CLASSIFICATION OF RECEPTORS
• Eg, tubulin, the receptor for colchicine, an anti-inflammatory drug
- STRUCTURAL PROTEINS
CLASSIFICATION OF RECEPTORS
• Eg, Na+/K+ ATPase, the membrane receptor for digitalis
- TRANSPORT PROTEINS
- Specific binding region of the macromolecule
- High and selective affinity to the drug molecule
- Interaction between the drug and the receptor is the fundamental event that initiates the action of the drug
RECEPTOR SITE/RECOGNITION SITE
- Same site as the endogenous ligand
* Drugs directly compete for the receptor site
ORTHOSTERIC SITE
- Different site
- Alters the response of the endogenous ligand binding to the ligand-gated ion channel and increase or decrease the flow of ions
ALLOSTERIC SITE
- Non-regulatory molecules of the body
- Binding with these molecules will result to no detectable change in the function of the biologic system
- Buffers the concentration of the drug
- Bound drugs do not contribute directly to the concentration gradient that drives diffusion
- Eg, albumin
INERT BINDING SITES
- Receptor-like proteins predicted from the human genome for which an endogenous ligand is not identified
- Target for the development of new drugs
ORPHAN RECEPTORS
In most cases, drugs bind to their receptor by forming (what kinds of bonds) bonds with a receptor site.
hydrogen, ionic, or hydrophobic (van der Waals)
- weak bonds
* reversible and enable the drug to dissociate from the receptor as the tissue concentration of the drug declines
HYDROGEN, IONIC, OR HYDROPHOBIC (VAN DER WAALS) BONDS
• Drug must bind to one stereoisomer only
STEREOSPECIFICITY
- A substance that can exist in the L or D form
* L may be the better drug
ENANTIOMER
- Drug having both the L & D form; cannot be separated
* Patient will experience both the therapeutic and toxic effects.
RACEMIC MIXTURE
- Binding is permanent, irreversible
* Prolonged duration of effect
COVALENT BOND
The weaker the bond, the more _____ it becomes.
selective
• Tendency of a drug to combine with its receptor is
• A measure of the strength of the drug-receptor complex
•
AFFINITY
↑ affinity, __ binding
↓
- Describes the pathway from ligand binding to conformational changes in the receptor, receptor interaction with an effector molecule (if present), and other downstream molecules called second messengers.
- This cascade of receptor-mediated biochemical events ultimately leads to a physiologic effect.
- Pathway for drug to enter the cell
SIGNAL TRANSDUCTION
- Ability of a drug to initiate a cellular effect
- Efficacy is not directly related to receptor affinity and differs among various drugs that bind to a receptor and start the signal transduction pathway.
EFFICACY OR INTRINSIC ACTIVITY
- Binds to the receptor and directly or indirectly bring about an effect
- Full activation of the effector system
- Both agonists and antagonists have common components sufficient for receptor affinity, but only agonists have the structure required for efficacy.
AGONIST
Drugs that have both receptor affinity and efficacy
AGONIST
Produce the maximal response obtainable in a tissue
FULL AGONISTS
agonists with maximal efficacy
FULL AGONISTS
agonists that Increase the rate of signal transduction when it binds to the receptor, whereas an inverse agonist
FULL AGONISTS
• agonists that Produce only a submaximal response
PARTIAL AGONISTS
agonists that Produces less than the full effect, even when it has saturated the receptors
PARTIAL AGONISTS
agonists Acts as an inhibitor in the presence of a full agonist
PARTIAL AGONISTS
- Also called negative antagonists
- Involved in a special type of drug-receptor interaction
- Decreases the rate of signal transduction
INVERSE AGONISTS
- Binds but do not activate the receptors
- Blocks or competes with agonist
- Prevent the action of agonists and inverse agonists by occupying binding sites on the receptor.
ANTAGONIST
- Response of a particular receptor-effector system is measured against increasing concentration of a drug
- Sigmoid curve
GRADED DOSE-RESPONSE CURVE
• Efficacy (Emax) and potency (EC50) are derived from this curve
GRADED DOSE-RESPONSE CURVE
- Graph of the response versus the drug dose
* Tells the EFFICACY of the drug
GRADED DOSE-RESPONSE CURVE
- Maximal Efficacy
* Potency
PARAMETERS OF THE GRADED-DOSE CURVE
- Maximal response that can be produced by a drug
- All receptors are occupied
- No response even if the dose is increased
Emax