Pharmacodynamics

Question 1

What are common enzyme targets for drugs?

Answer 1

Regulatory (change activity of enzymes)
Enzymes (inhibit or activate)
Transport (Na/K ATPase)
Structural (form cell parts- i.e. cancer therapy)

Question 2

How do drugs work?

Answer 2

Typically act on receptors
On cell surface or intracellularly
Form tight bonds with receptors (can be covalent (irreversible typically) or ionic)
Meet size requirements

Question 3

What are types of drugs receptor targets?

Answer 3

Enzymes linked (multiple actions, commonly drugs are inhibiting their action)
Ion channel linked (speedy)
G Protein linked (amplifier)
Nuclear (gene) linked (long lasting- always end up in nucleus- take much longer to take effect compared to surface receptors)

Question 4

What is Bisoprolol and how does it work (include target receptor type)?

Answer 4

Beta Blocker
Acts on adrenaline receptors (GCPR adrenoreceptor), preventing adrenaline binding and resulting intracellular signalling pathway
Results in decreased HR and cardiac contractility

Question 5

What is clarithromyocin and how does it work?

Answer 5

Macrolide class of antibiotic
Binds 50S subunit of bacterial ribosome, inhibiting ribosomal function and preventing amino acids from being added to the forming protein

Question 6

What is Suxamethonium and how does it work?

Answer 6

Stimulates acetylcholine receptors continuously for a period of a minutes, leading to saturation of signalling at the neuromuscular junction causing unresponsiveness of AchR until the effects wear off, usually after around 5-10 minutes.
Rapid onset- ligand gated ion channel
Used as general anaesthetic

Question 7

What is Prednisolone and how does it work?

Answer 7

A corticosteroid drug, with long onset time.
Works by mimicking endogenous steroids, and binds to intracellular receptors, activating DNA transcription and translation to inhibit inflammation

Question 8

What is affinity, and what are the types of affinity?

Answer 8

Measure of propensity of a drug to bind receptor; attractiveness of drug and receptor
Covalent bonds- stable, irreversible
Electrostatic bonds- strong or weak, reversible

Question 9

What is drug efficacy?

Answer 9

Ability of a bound drug to change the receptor in a way that produces an effect.
You can have affinity but no efficacy

Question 10

What is potency and how does it shift the dose response curve?

Answer 10

Achieving given effect at a specific concentration.
High potency achieves effect at lower concentrations
High potency sits more to the left, whereas low moves to the right.

Question 11

What is an agonist?

Answer 11

Binds to and activates the receptor

Has affinity and efficacy

Question 12

What is an antagonist?

Answer 12

Binds to and does not activate the receptor.

Has affinity but no efficacy

Question 13

What is a partial agonit?

Answer 13

Could potentially function as agonist or antagonist (modest efficacy)

Question 14

What are competitive antagonists?

Answer 14

Compete for control of receptor- this is because it is typically electrostatic binding
Efficacy of agonist is not reduced, but apparent potency of agonist is lost (due to competition). As long as high enough concentration of agonist is given, maximal efficacy will still be seen.

Question 15

What is dextral shift?

Answer 15

Competitive antagonist displaces the dose-response curve to the right and reduces the apparent affinity of the agonist
Can be overcome with higher agonist concentration

Question 16

What are non-competitive antagonist?

Answer 16

Use covalent bonding (or tight irreversible electrostatic binding) to irreversibly bind the receptor.
Causes reduction in potency, apparent potency, and apparent efficacy. This is because they are irreversibly bound to the receptor, so agonist dosing will not change outcome.

Question 17

What are types of adverse reactions?

Answer 17

Type A; Common, predictable, usually dose-related, uncommonly life-threatening, plotted as a curve (can get range of reactions and severity)
Type B: Uncommon, unpredictable, not usually dose related, often life threatening, typically either get the response or do not.

Question 18

What is ED50?

Answer 18

Median Effective Dose- dose at which 50% of population manifests a given effect

Question 19

What is TD50?

Answer 19

Median Toxic Dose- dose at which 50% of population manifests toxic effect

Question 20

What is LD50?

Answer 20

Median Lethal Dose- dose which kills 50% of the population

Question 21

What is the therapeutic index?

Answer 21

Ratio of LD or TD 50 to the Effective Dose.

Higher TI is better as it means larger space between safe dosing and dose which causes death/toxic effect.

Question 22

What are examples of drugs with large TI and low?

Answer 22

Penicillin has high therapeutic index and high doses are typically safe
Chemotherapy has low, and side effects are expected.