Basics

Question 1

What is the difference between covalent, electrostatic and hydrophobic bonds?

Answer 1

Covalent: Strong. Non usually reversible. E.g. aspirin
Electrostatic: ionic molecules vs hydrogen bonds
Hydrophobic: Weak. ?Highly lipid soluble drugs

Question 2

Define - full agonist, partial agonist, inverse agonist, antagonist

Answer 2

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

Question 3

What are the 4 ways drugs permeate?

Answer 3

1. Aqueous Diffusion: Fick’s Law
2. Lipid Diffusion: Henderson-Hasselbalch Equation
3. Special Carriers: Active transport or facilitated diffusion
4. Endocytosis/Exocytosis

Question 4

What is Fick’s Law?

Answer 4

Question 5

What is Henderson-Hasselbalch’s equation?

Answer 5

More of a weak acid will be soluble at acid pH and basic drug will be soluble at alkali pH.

Question 6

What is the concentration-effect curve?

Answer 6

Drug response is usually proportional to drug dose. The response increment diminishes with drug increases until plateau.

Question 7

Draw the dose-response curves for a full agonist, partial agonist, antagonist and inverse agonist.

Answer 7

Question 8

What are 5 different mechanisms of transmembrane signally?

Answer 8

Intracellular lipid soluble, ligand-regulated transmembrane enzymes, cytokine receptors, ion channels, G proteins/secondary messengers

Question 9

How do intracellular receptors for lipid soluble agents work?

Answer 9

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

Question 10

How do ligand-related transmembrane enzymes work?

Answer 10

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

Question 11

What are cytokine receptors?

Answer 11

Ligand binds to receptor’s extracellular component -> dimerise -> extrinsic JAK activation -> STAT binding/dimerisation the disssocation
e.g. growth hormone, EPO, IF

Question 12

What are ion channels?

Answer 12

Receptors increase transmembrane conduction of iron to alter electrical potential

e.g. ACh, 5HT, BAGA, glutamate

Question 13

What are secondary messengers?

Answer 13

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

Question 14

What is potency and maximal efficacy?

Answer 14

Potency: The concentration (EC50) or dose (ED50) of a drug required to produce 50% max effect
Maximal Efficacy: Limit of dose-response relation

Question 15

How do you measure adverse effects?

Answer 15

TD50 - toxicity experienced in 50% of population
LD50 - death experienced in 50% population

Question 16

How do you determine drug doses?

Answer 16

Therapeutic Index: Ratio of TD50 to ED50
Therapeutic Window: Minimum toxic dose and minimum therapeutic dose range - determined by clinically acceptable toxicity/disease severity

Question 17

What causes variations in drug responsiveness?

Answer 17

• 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