Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

Study of action of drugs on the body

Question 2

What is pharmacokinetics?

Answer 2

Study of what the body does to the drug

Question 3

What is the generic name of a drug?

Answer 3

Non-proprietary name that each chemical can be given

Question 4

What is the trade name of a drug?

Answer 4

Proprietary name, owned by company

Question 5

Targets of drug action

Answer 5

Proteins, DNA, lipids

Question 6

What do inotropic receptors do?

Answer 6

Facilitate movement of ions across membranes

Require ligand binding - transient interaction

Question 7

Characteristics of ionotropic receptors

Answer 7

• Require ligand binding - transient interaction (binding and dissociation happens rapidly)
• Hyperpolarization or depolarization of cell
• Typically penatameric
• Pore in centre allows ions to flow
• Signalling time is very fast - milliseconds

Question 8

Characteristics of G-protein coupled receptors

Answer 8

• Largest family
• Metabotropic receptors
• 7 transmembrane domains
• N-terminal domain is where drug binds
• C terminal where G protein signaling takes place
• Activating protein can influence ion channel activity or activate second messenger cascade
• Ion channel excitability
• G alpha s and G alpha I act via same secondary messenger
• AC = adenylate cyclase, which catalyses of ATP to cAMP which influences PKA
• G alpha I inhibits adenylate cyclase - negative effect cAMP and PKA
• G alpha q activates phospholipase C which catalyses PIP2 to DAG and IP3
• DAG and IP3 influence PKC
• IP3 is calcium regulator

Question 9

How do kinase linked receptors work?

Answer 9

• Single membrane spanning domain
• Dimerization when drug binds
• When drug binds, autophosphorylation of tyrosine kinase domain
• Dimerization attracts intercellular proteins to express SH2 domain to activate targets, most common target is Ras/Raf/MAPK or Jak/Stat pathway

Question 10

Characteristics of nuclear receptors

Answer 10

• Nuclear or cytosolic
• Ligands lipid soluble
• Act as transcription factors
• Take hours
• e.g. oestrogen receptor
• Mainly steroids or hormones
• Receptor activated when ligand binds
• Nuclear receptors can increase or decrease gene expression

Question 11

What is drug specificity?

Answer 11

Binds selectively to particular receptor types

Question 12

What do agonists do?

Answer 12

Activate receptors

Question 13

What do antagonists do?

Answer 13

Block receptors, often inhibit endogenous agonist action

Question 14

What is the binding affinity?

Answer 14

How well does the drug bind to the receptor

Question 15

What is efficacy?

Answer 15

Ability of drug to bring about full response

Question 16

What is a full agonist?

Answer 16

Elicit 100% of endogenous agonist

Question 17

What is a partial agonist?

Answer 17

Elicits <100% effect

Question 18

What is a super agonist?

Answer 18

> 100% of endogenous effect

Question 19

What is an inverse agonist?

Answer 19

Reduce basal receptor activity

Question 20

What is potency?

Answer 20

Agonist drug potency is a product of affinity and efficacy

Question 21

What is an equipotent molar ratio?

Answer 21

Picking a threshold and observing concentration required to get that response

Question 22

Why don’t antagonists activate receptors?

Answer 22

They have zero efficacy

Question 23

What are receptor antagonists?

Answer 23

Reversible or irreversible - competitive (reversible) but can be competitive or uncompetitive

Question 24

What are non-receptor antagonists?

Answer 24

Chemical, physiological (produce opposite effect of agonist, e.g. insulin and glucagon) and pharmacokinetic (influencing action of one drug by modifying its pharmacokinetic profile)

Question 25

What are uncompetitive antagonists?

Answer 25

Endogenous compound binds, allowing antagonist to bind at alternative site

Question 26

What is an irreversible agonist?

Answer 26

Occupy and bind to receptors which reduces available receptors for agonists to bind - no response in extreme

Question 27

When will full agonists bring about maximum effect?

Answer 27

Binding to 20% of receptors

Question 28

What is EC50?

Answer 28

Dissociation constant for drug

Question 29

What is pharmacogemonics?

Answer 29

Genetic variability in the way drugs behave in the body

Question 30

What is pharmacokinetics?

Answer 30

Enzyme polymorphism

Question 31

What is desensitization?

Answer 31

A drug's effectiveness may decrease rapidly when given repeatedly or continuously

Question 32

What is tolerance?

Answer 32

Decrease in a drug's effectiveness over days or weeks

Question 33

What is resistance?

Answer 33

Adaptive change = less effective = enhanced or decreased drug metabolism,

Question 34

Drug factors affecting efficacy of drug

Answer 34

Pharmacokinetics and pharmacodynamics

Question 35

What is PCA?

Answer 35

Patient regulates dosing and becomes excessive if too drowsy Dose sizes and lockout intervals introduced to ensure time allowed for drug to work

Question 36

Why might the outcome of a drug not be measured easily?

Answer 36

- Long delay in seeing result - Multi-factorial condition - Examples: immunizing against disease, preventing ischemic heart disease, weight loss therapy