Basics Flashcards
What is the difference between covalent, electrostatic and hydrophobic bonds?
Covalent: Strong. Non usually reversible. E.g. aspirin
Electrostatic: ionic molecules vs hydrogen bonds
Hydrophobic: Weak. ?Highly lipid soluble drugs
Define - full agonist, partial agonist, inverse agonist, antagonist
Full: Activates receptor to maximum effect when concentrations saturate
Partial: Activates receptor to some effect when concentrations saturate
Inverse:
Antagonist: Block agonist access to receptor
Inverse: I Activates receptor and reduces activity
What are the 4 ways drugs permeate?
- Aqueous Diffusion: Fick’s Law
- Lipid Diffusion: Henderson-Hasselbalch Equation
- Special Carriers: Active transport or facilitated diffusion
- Endocytosis/Exocytosis
What is Fick’s Law?
What is Henderson-Hasselbalch’s equation?
More of a weak acid will be soluble at acid pH and basic drug will be soluble at alkali pH.
What is the concentration-effect curve?
Drug response is usually proportional to drug dose. The response increment diminishes with drug increases until plateau.
Draw the dose-response curves for a full agonist, partial agonist, antagonist and inverse agonist.
What are 5 different mechanisms of transmembrane signally?
Intracellular lipid soluble, ligand-regulated transmembrane enzymes, cytokine receptors, ion channels, G proteins/secondary messengers
How do intracellular receptors for lipid soluble agents work?
Biologic ligands are sufficiently lipid-soluble to cross the plasma membrane.
Lag time 30m-hours (protein synthesis time). Effect can last for hours-days following agonist = 0
e.g. steroids
How do ligand-related transmembrane enzymes work?
Ligand binds to receptor’s extracellular component -> dimerise -> tyrosine kinase/serine/guanylyl activation -> receptor phosphorylation
Down regulation - accelerated endocytosis of receptors
e.g. insulin, EGF, TGF-b
What are cytokine receptors?
Ligand binds to receptor’s extracellular component -> dimerise -> extrinsic JAK activation -> STAT binding/dimerisation the disssocation
e.g. growth hormone, EPO, IF
What are ion channels?
Receptors increase transmembrane conduction of iron to alter electrical potential
e.g. ACh, 5HT, BAGA, glutamate
What are secondary messengers?
Ligand is detected by receptor -> triggers G protein -> changes activity of effector element -> changes concentration of intracellular second messenger.
e.g. cAMP -> glucagon/norad/caffeine, DAG->PKC, IP3->Ca
What is potency and maximal efficacy?
Potency: The concentration (EC50) or dose (ED50) of a drug required to produce 50% max effect
Maximal Efficacy: Limit of dose-response relation
How do you measure adverse effects?
TD50 - toxicity experienced in 50% of population
LD50 - death experienced in 50% population
How do you determine drug doses?
Therapeutic Index: Ratio of TD50 to ED50
Therapeutic Window: Minimum toxic dose and minimum therapeutic dose range - determined by clinically acceptable toxicity/disease severity
What causes variations in drug responsiveness?
- alterations in concentration of drug that reaches the receptor
- variation in concentrations of receptor ligand
- alterations in number and function for receptors
- changes in components of response distal to the receptor
