6.9 Pharmacodynamics and Drug Receptor Mechanisms Flashcards
What are common biologic targets for drugs?
1) Enzymes (activate/inhibit)
2) Receptors (G protein coupled; Tyrosine Kinase)
3) Ion channels
4) Transport proteins
5) DNA/RNA and ribosomes
6) Targets of monoclonal antibodies
What determines the magnitude of the response?
Depends on the number of receptors/drug interactions.
Describe receptor states
Receptors have active state and inactive states, most receptors work slightly even without ligand. The inverse agonist completely shuts this basal level off.
Which bond is the strongest?
Covalent bonds
What are other types of bonds?
- Electrostatic-more common but not as strong as covalent.
1) Ionic bonds
2) Hydrogen bonds
3) Dipole interaction - Hydrophobic bonds
Describe the effects of receptors on drug effectiveness.
- Receptors are responsible for selectivity of drug action.
- Receptors mediate the actions of pharmacological agents.
- Receptors determine quantitative interaction between dose or concentration and pharmacological effects.
- Components of a cell or organism that interacts with a drug and initiates activity that leads to observed effects.
What is a full agonist?
Stimulates maximum effect
What is a partial agonist?
Stimulates partial effect
What is an inverse agonist?
Binds to a receptor and causes an opposite effect of the agonist, turns off basal activity of receptors.
What is an antagonist?
Binds to the receptor compete with and prevent binding by other molecules.
What are the two types of antagonist?
Competitive and non-competitive
Describe a competitive antagonist
- Binds to active site and prevents agonist from binding.
- reversible
Describe a non-competitive antatgonist
- Can bind to an active site or allosteric site and blocks binding.
- Irreversible
- Binds active site with covalent bond or high affinity
- At allosteric site prevents receptor activation by agonist.
What is a non-receptor antagonist?
- Chemical- two drugs combine and neutralize activity. Example Protamine (basic) binds to heparin (acid)
- Physical- Receptor is activated facilitates an effect that is opposite of the antagonist.
What does it mean if a molecule is chiral?
- Chiral substances possess a unique architecture such that despite sharing identical molecular formulas, atom-to-atom linkages, and bonding distances, they cannot be superimposed.
- Must have 4 unique side chains.
What handedness are most sugars?
D-sugars
What handedness are all amino acids for life?
L-amino acids
What direction is chiral L?
Counter-Clockwise
What direction is chiral D?
Clockwise
What is the most important amino acid?
Glutamate
How are most drugs sold in relation to chirality?
Racemix 50/50
What is tolerance?
Occurs when responsiveness decreases as a consequence of continued drug administration
What is tachyphylaxis?
Rapid appearance of progressive decrease in response to a given dose after repetitive administration of a pharmacologically or physiologically active substance.
What is desensitization?
When receptors and cell response diminishes by a drug or ligand, can have underlying tolerance but does not have to.
What is homologous desensitization?
Decrease response at a single type of receptor
What is heterologous desensitization?
Decreased response at two or more receptors
What is refractoriness?
State when time is required to pass before receptor can be stimulated again. Example voltage gated sodium channels
What is down-regulation?
Prolonged stimulation leads to endocytosis and sequestration of receptors.
