Pharmacodynamics Flashcards
Pharmacology
Study of substances interacting with living systems chemically
Medical Pharmacology
Study of substances used to prevent, diagnose, and treat disease
Toxicology
Study of undesirable effects of chemicals on living systems and ecosystems
Pharmacodynamics
what drugs do to the body
Pharmacokinetics
what the body does to drugs
Properties required for drug to interact chemically with its receptor
Size, electrical charge, shape, atomic composition
Shape
drug shape complimentary to receptor ‘site’
Size
Varies b/w 100-1000 MW
Atomic composition consists of
- Organic compounds (carbohydrates, proteins, lipids, acids/bases)
- Inorganic compounds (lithium, iron)
ADME
Absorption, distribution, metabolism, excretion
Intravenous (IV)
Needles, most rapid onset
Intramuscular (IM)
Large volumes, may be painful
Subcutaneous (SC)
Skin, smaller volumes than IM, may be painful
Oral (PO)
Most convenient, significant first-pass effect
Transdermal
Very slow absorption, prolonged duration of action, used for minimal first-pass effect
Parenteral Rectal (PR)
Less first-pass effect than PO
Inhalation
Often very rapid onset
Drug-Receptor Bond types
covalent, electrostatic, hydrophobic
Covalent
Very strong bond, not reversible biologically in most cases
Electrostatic bonds
Common bond involving charged ionic molecules, H-bonds, dipole
Hydrophobic bond
Weak bond involving highly lipid-soluble molecules
Rational drug design uses
Computer programs designed to fit 3D structure of receptor site
Agonist (def+example)
Binds to and activates receptors
Eg. opening of ion channel, enzyme activation
Partial agonist
Agonist with less activation than a full agonist
Inverse agonist
Stabilizes receptors in an inactive form, reducing activity
Antagonist
Binds to receptor, competes/prevents binding of other molecules
Competitive Antagonist
Antagonist that binds to the same site as the natural ligand
Noncompetitive Antagonist
Antagonist that binds to a different site on the receptor (allosteric)
Irreversible Antagonist
Antagonist that covalently modifies the receptor
Best characterized drug receptor is
Regulatory G-protein coupled receptors
Duration of Drug Action
Effects last as long as drug occupies receptor
If a covalent bond, drug effect:
persists until drug-receptor complex destroyed/new receptors synthesized
Concentration-Effect Curves show that
Responses to low dose and dosage are directly proportional
Why are drugs reported on a log scale?
Easier to differentiate between 2 drugs you’re comparing
Pharmacologic Potency (and what axis is it based on)
Required concentration or dose to create 50% of drug’s maximal effect, based on dose-response curves along dose axis
Maximum efficacy (and what axis is it based on)
maximum biological effect, based on dose-response curves along response axis
EC50
Concentration of drug required to produce 50% max effect
ED50
Dose of drug required for 50% of individuals to exhibit therapeutic effect
IC50
Half maximal inhibitory concentration - inhibits specific biological or biochemical function by 50%
Kd
Concentration of a free drug where half-maximal receptor binding is observed
High Kd means
binding affinity is low
Low Kd means
binding affinity is high
Spare Receptors
Unbound receptors when an agonist is producing maximal response
TD50
Dose where 50% of individuals show a toxic side-effect
LD50
Dose where 50% of subjects die
TI
Therapeutic index: TD50/ED50
TI50
dose of drug required to produce desired effect without undesired effect
Drug Signaling Mechanisms (5)
- Intracellular receptor
- Extracellular receptor
- Extracellular receptor activates separate tyrosine kinase
- Direct regulation of ion channel
- Cell surface receptor linked to effector enzyme by G-protein
Intracellular receptor mechanism
A lipid-soluble ligand crosses the membrane and acts on an intracellular receptor
Extracellular receptor/Extracellular receptor activates tyrosine kinase mechanism
A transmembrane receptor protein that has enzymatic activity OR stimulates a protein tyrosine kinase
Cell surface receptor linked to effector enzyme by G-protein mechanism
A transmembrane receptor protein stimulates a GTP-binding signal transducer protein (G-protein) that modulates an intracellular second messenger
Direct regulation of ion channel mechanism
A ligand-gated transmembrane ion channel can be induced to open or close
