L2 Pharmacodynamics and Bio Site Flashcards
what type of bond is ideal for for drugs binding to receptor
Electrostatic
-Van der waals and Hydrogen
- You DON’T WANT covalent bond
how do drugs cause adverse (side) effects
act not only at site intended but also at other sites (side effects)
Describe the Philadelphia Chromosome
translocation between chromosome 9 and 22
What is the treatment for Philadelphia Chromosome
- Imatinib- when it binds via hydrogen/ van der waals bonds, it prevent the conversion of kinase enzyme
Imatinib causes less side effects because of the specificity for that receptor and enzyme indicated for chronic myeloid leukemia
MOA: highly selective inhibitor of BCR- ABl tyrosine kinase that is encoded by Philadelphia Chromosome
Over next month the cells containing the Philadelphia Chromosome disappear
What are the 4 types of drug receptors
-Transmembrane Ion Channel
-Transmembrane Linked to Intracellular G- Proteins (GDP)
-Transmembrane with Enzymatic Cytosolic Domain withIntracellular or Extracellular Enzyme adhesion
-Diffusion (steroid molecules)
What is the main ligand for the nicotonic receptor
Acetylcholine
Ligand-Gated Nicotinic Acetylcholine Receptor is what type of receptor
Transmembrane Ion channel
-sodium is associated with receptor
Describe the Ligand-Gated Nicotinic Acetylcholine Receptor
-Has a total of 5 subunit
2 alpha, 1 Beta, 1 Gamma, and 1 Delta
-Acetylcholine binds to the alpha subunit, causes channel to open
-sodium transverse through the channel when the channel opens
-A drugs whose mechanism of action is to block sodium are local anathetics, therefore sodium does not go through the channel. Ex: benzodiazepine
Describe Receptor-Mediated Activation of a G Protein and the Resultant Effector Interaction
-It is heptahelical structure spanning the membrane
-GTP to GDP
-Ex; Beta 1,2,3 receptor, Dopamine receptor, Seratonin receptor, opoid receptor
What is an example of a molecule for Transmembrane Receptors with Enzymatic Cytosolic Domains
Insulin
B adrenergic receptor
-Agonist is norepineherine (increase HR)
-Antagonist is propranolol (net effect is decrease HR)
Magnitude of response is dependent on…
the concentration of the agonist at the receptor site [L] - Measurable
Magnitude of response is…
proportional to number of drug-receptor complexes
[LR]- Measurable
difference between Graded Dose-Response Curve and Quantal Dose-Response Curve
◼Graded Dose-Response Curve Response vs. Dose in a single individual (R vs [L])
◼Quantal Dose-Response Curve %Patients Responding vs. Dose in a group of individuals; Response is QUANTIZED
Reduced responsivity:
Chronic use of an agonist can result in the receptor- effector system becoming less responsive
– eg. alpha-adrenoceptor agents used as nasal decongestants
Myasthenia gravis: decrease in number of functional acetylcholine nicotinic receptors at the neuromuscular junction.
Competitive inhibitor
Compete for the
binding site. Response is
shifted to the right.
Non-competitive Inhibitor
Prevent agonist binding or prevent agonist from
activating the receptor
Partial agonist
Produces smaller effect than a full agonist and antagonizes a full agonist
Efficacy
is the maximal response produced by a drug
-depends on number of drug- receptor complexes and the efficiency
Potency
◼ Also called effective dose (ED) concentration
◼ Potency is a measure of how much drug is required to elicit a given level of response
◼ Potency is expressed as the dose that
gives 50% of E (called ED 50)
Therapeutic Index
Toxic Dose/Effective Dose
- Measure of the drug’s safety
- Large value indicates a wide margin between doses that are effective and doses that are toxic.
-Examples
: Warfarin has narrow index
(~2). Penicillin has large therapeutic window (10x)
Tachyphylaxsis
Rapidly emerging tolerance
* Will not work with 1-2 hours
* Ie Bretylium`
