Pharmacology Flashcards
(31 cards)
Pharmacodynamics vs Pharmacokinetics
What drugs do to the body: includes duration and response magnitude
What the body does to the drugs (ADME): absorption, distribution, metabolism, elimination
Terfenadine (Seldane)
Marketed as a specific H1 receptor antagonist (anti-histamine) that did not cause drowsiness
1980s and 90s, for allergies
In livers with impaired metabolic functions terfenadine (pro drug) cannot convert to fenofexodine
Liver enzymes convert terfenadine to fexofenodine
Terfenadine can block potassium ion channels that contribute, electrical activity of the heart, lead to abnormal cardiac rhythms.
Allergra (fexofenodine) was the solution to this, avoids cardio toxic effects of terfenadine
Pharmacogenomics
The genetic background can affect how a patient can respond to a drug
Receptor theory
1) target proteins (receptors) need high affinity for its endogenous ligand
2) an early recognizable chemical event must occur following ligand binging to receptors
3) receptors must possess specificity for ligands
4) receptors are saturable and finite (limited number if binding sites)
equilibrium between bound and unbound proteins to produce change in state of protein, which reversible translates to a physiological effect (most times)
If ligand binds covalently to a receptor, it is an irreversible electrostatic interactions
Hill Langmuir equation
When [A] = Kd, the concentration of drug [A] is just enough to occupy half the receptors
Receptors
Proteins that respond to an external stimulus and induce a change inside the cell
Channels
Form pores in cell membrane to allow passive movement of ions into or out of the cell
Passive diffusion (concentration gradient)
Transporters
Actively transport molecules across the membrane
Intracellular receptors
Receptors that are inside the cell
Drug needs to be able to cross into the plasma membrane; must be lipid soluble (e.g. steroid hormones)
Which GPCR alpha subunits for adenylate cyclase (AC)
(Converts ATP to cyclic AMP, regulates downstream activities of the cell)
Gs, Gi
Which GPCR alpha subunits influence phospholipase C (PLC)
Gq
On a dose response curve: EC50
Effective concentration 50
concentration of drug that yields a 50% maximal effect
On a dose response curve: Emax
Maximal biological effect observed with the dose response curve
Efficacy
Emax
Refers to the maximal drug effect
Potency
EC50
Concentration dependence
A drug with strong potency has
Low EC50 (small concentration needed to generate a large effect)
Agonists are categorized based on efficacy
Full agonist: generate maximal observed effect
Partial agonists: generates a sub maximal effect, regardless of dose
Inverse agonists: causes suppression of basal activity (antagonists)
Antagonists
Type of receptor ligand that blocks a biological response
Blocks receptors
Either competitive or non competitive
Competitive antagonists
Competitive antagonism (I) occupies the same binding site as the agonist (A) but does not elicit a biological response
At high enough concentrations, the antagonist is displaced and maximal efficacy can be achieved (surmountable antagonist)
Schild plot
Based off the dose ratio (concentration ratio)
Dose ratio is the ratio of agonist EC50 in the presence vs absence of antagonist
Dose ratio = agonist EC50 with agonist / agonist EC50 with no agonist
Competitive antagonists exhibit a linear Schild plot
X intercept (Pki) reflects antagonist potency (higher Pki = higher potency)
Irreversible competitive antagonists (non competitive antagonism)
Antagonist binds covalently
How do irreversible antagonists affect efficacy and potency
Reduce agonist efficacy and no effect on potency
How does a competitive antagonists affect efficacy effect amount of agonist concentration needed and agonist efficacy
Higher concentration of agonist needed to generate response but agonist efficacy not changed
Name of binding pocket for allosteric ligands
Orthosteric site
