Basic Principles of Pharm part 2 Flashcards
Agonist Mimics
Has the same effect as the agonist on the receptor, but works somewhere else (see explanation/picture in lecture 2 at 0:04:15)
Irreversible antagonist
Covalently bind to receptor and do not come off. The only way to get rid of it is to get rid of that receptor. Can be allosteric or orthosteric.
Partial agonist
Will bind to the active site and elicit a partial response. They compete for the same active site as a full agonist. (see lecture 2 @ 0:12:27)
How can a partial agonist act as an antagonist?
The full and partial agonists compete for the same site. If the partial agonist takes up the receptor sites, it is not allowing the full agonist to bind therefore, you don’t have the max response you could have.
Partial agonist by itself VERSUS partial agonist in presence of full agonist
Partial is an agonist by itself.
Partial is an antagonist in the presence of a full agonist.
Opposite charge antagonist example
Heparin (-) binds to Protamine (+) rendering heparin ineffective (has nothing to do with binding to receptors, has everything to do with drug-to-drug interaction in bloodstream)
Physiologic antagonism
Drugs acting at different receptors that counter act each other (ex: Epi binding to Beta and acetylcholine binding to muscarinic)
Receptor configuration: unbound
Ri (inactive) Ra (active)
can switch on and off spontaneously
Receptor configuration: bound with agonist
Ri –>Ra
favors active state
Inverse agonist (and example)
Ri
Sympathetic nervous system (SNS)
Fight or flight
Parasympathetic nervous system (PSNS)
Rest and digest
Factors that determine the duration of a drugs effects:
- As long as the drug stays bound to receptor.
- If a drug initiates the production of a protein, it will take longer to see effects and longer for response to stop.
- Receptor is degraded (in covalent bonding)
- Desensitization
Good receptor properties:
- Selective
- Alteration
Bad receptor properties:
- “Inert binding sites” (non-selective)
- Drug carriers (don’t elicit a response)
Potency
A drug is potent when it requires a very low dose to elicit 50% of that drugs maximal effect (Or its EC50).
If a drugs EC50 is low..
..the drug is very potent.
Efficacy
The maximal response you will see from a particular drug (see lecture 2 at 0:33:05)
ED50
Median effective dose
TD50
Median toxic dose
LD50
Median lethal dose
EC50 vs ED50
EC50: The concentration of drug in blood.
ED50: The actually dose being given.
Therapeutic index
Establishes the margin of safety of a drug.
TD50/ED50
The higher the Therapeutic Index..
..the safer the drug.
Idiosyncratic
means we don’t know why one patient responds differently to a drug than another patient
Tolerance
Response changes over the course of time
Tachyphylaxis
Quick tolerance
Causes of variation:
- Alteration in concentration of drug that actually reaches the receptor (rate of absorption/distribution/clearance, age, weight, sex, disease state)
- Concentration of endogenous ligand (maybe affected by health or disease
- Alteration in function and number of receptors
- Changes in components of response distal to receptor (largest and most important cause)
Toxic effects
Some drugs produce both desired and adverse effects at the same receptor. other drugs bind to different classes or receptors
Pharmacokinetics: ADME:
Absorption
Distribution
Metabolism
Elimination
4 main ways a drug will permeate through the body:
Aqueous diffusion Lipid diffusion Special carriers Endocytosis and exocytosis (*all of these depend if drug is charged/uncharged and size)
Aqueous diffusion
Larger aqueous compartments in body (ex: blood)
Cells may have aqueous channels
Diffusion by concentration gradient
Molecules can be large
Not aqueous diffusion
Highly charged molecules
Bound to large proteins (carriers)
Lipid diffusion
Easiest to cross barriers
example: gases
Special carriers
Protein that will bind to a drug and move it from one area to another.
Use active transport (energy required) or facilitated diffusion
In Fick’s law of diffusion, flux is…
..how fast a drug will move from one side of a barrier to another
Flux is largely dependent on..
..concentration gradient.
If the concentration of one side of a barrier is significantly more than on the other side, what will happen to the flux? (Fick’s law)
The flux will be very large
If the surface area of a barrier is very large, what will happen to the flux? (Fick’s law)
The flux will be very large
If a barrier is very thick, what will happen to the flux? (Fick’s law)
The flux will be very small
Endocytosis
Exocytosis
Membrane engulfment of molecule
Can be receptor mediated
Slow process
Very large or charged molecules
Merging of vesicle with membrane
Henderson Hasselbach Equation
pH= pKa + log [A-]/[HA]
If pH = pKa..
..the ratio of ionized versus unionized is equal
If pH < pKa..
..favors protonated form
If pH > pKa..
..favors un-protonated form
What part of the kidneys are most drugs filtered at?
Glomerulus
Concentration of drug in renal tubules is dependent on what?
pH
“Trapping” drugs in urine:
Weak acids excreted faster in..
Alkaline urine
“Trapping” drugs in urine:
Weak bases excreted faster in..
Acidic urine
