Introduction

Question 1

What is pharmacodynamics?

Answer 1

What the drug does to the body

• mechanism of drug action
• cellular and systemic effects

Question 2

what is pharmacokinetics? what are the components of it?

Answer 2

What the body does to the drug

• absorption
• distribution
• metabolism
• excretion

Question 3

what is pharmacotherapeutics? what should you consider?

Answer 3

the use of drugs to prevent and treat diseases.

consider the beneficial effects and adverse effects of the drug

Question 4

what are some general examples of drug targets?

Answer 4

Receptors, enzymes, carriers/transporters, ion channels

Question 5

Compare and contrast agonists and antagonists

Answer 5

Agonists activate drug targets and mimic or increase physiological responses and effects

antagonists block drug targets and inhibit or decrease physiological responses and effects

Question 6

what are the two ways drugs can act on drug targets

Answer 6

reversibly (competitively)

irreversibly (non competitively)

Question 7

What are the four types of receptors?

Answer 7

• ligand gated ion channels (ionotropic) e.g. nicotinic AcH receptor
• G protein coupled receptors (metabotropic) muscarinic AcH receptor
• kinase linked receptors e.g. cytokine receptors
• nucelar receptors e.g. oestrogen receptor

Question 8

Describe G protein coupled receptors

Answer 8

• most common drug target
• integral membrane protein
• coupled with a G protein

Question 9

what is the function of the G protein in the coupled receptor?

Answer 9

• acts as a molecular switch inside cells
• involved in transmitting signals from a variety of stimuli outside to its interior
• activation of the receptor activates the G protein OR inhibits a second messenger

Question 10

What are some targets of the G protein coupled receptors

Answer 10

Adenylate cyclase

Phospholipase C

Question 11

What is adenylate cyclase?

Answer 11

The enzyme responsible for catalysing the formation of CAMP, which regulates many aspects of cellular function by the activation of protein kinases.

Question 12

What does cAMP activate?

Answer 12

protein kinases, which in turn regulate the function of many different cellular proteins by controlling phosphorylation (which can activate or inactivate various proteins)

Question 13

What is the impact of adenylate cyclase on cardiac muscle?

Answer 13

Adenylate cyclase catalyses cAMP which activates protein kinases, which control phosphorylation.

In cardiac muscle the phosphorylation of voltage gated Ca2+ channels increases their permeability to Ca2+, increasing influx during the action potential, thus increasing the force of contraction

Question 14

What is the impact of adenylate cyclase on smooth muscle?

Answer 14

Adenylate cyclase catalyses cAMP which activates protein kinases, which control phosphorylation.

In smooth muscle, phosphorylation inactivates the enzyme myosin-light chain kinase (MLCK) which is required for contraction, thus causing relaxation

Question 15

What is the role of phospholipase C?

Answer 15

Catalyses the formation of inositol triphosphate (IP3) and diacylglycerol (DAG) which have important cellular functions

Question 16

What is the role of IP3?

Answer 16

Catalysed from phospholipase C, it is a mediator in the cytoplasm that acts on the IP3 - a ligand gated Ca2+ channel on the membrane of the ER.

When this is activated, the Ca2+ channel is opened and stores are released in the cytoplasm initiating events including

• contraction
• secretion
• enzyme activation
• membrane hyperpolarisation

Question 17

What happens when the IP3 receptor is activated?

Answer 17

the Ca2+ channel is opened and stores are released in the cytoplasm initiating events including

• contraction
• secretion
• enzyme activation
• membrane hyperpolarisation

Question 18

What is the role of DAG?

Answer 18

Activates protein kinase C, which controls many cellular functions by phosphorylating a variety of intracellular proteins

Question 19

What are the G protein subtypes and their functions?

Answer 19

Gαs - stimulates adenylate cyclase, increasing cAMP formation

Gαi - inhibits adenylate cyclase, decreasing cAMP formation

Gαo - limited effect of alpha subunit

Gq - actiavtes phospholipase C, increasing production of second messengers IP3 and DAG

Gβγ - activates potassium channels, inhibits voltage gated Ca2+ channels, activates GPCR kinases, activates mitogen activated protein kinase cascade, interacts with some forms of adenylate cyclase and phospholipase Cβ

Question 20

What are the different levels of drug effects?

Answer 20

Drug molecule
- administration

Cell
- cellular effects e.g. depolarisation, contraction

tissue and organ effects
- e.g. decreased cardiac muscle contractility

physiological system
-e.g. decreased BP

individual
- clinical effects e.g. reduced hypertension

population and society
- pharmacoepidemiology and pharmacoeconomics e.g. disease prevalence and health care costs

Question 21

what is an indication?

Answer 21

a disease or condition that warrants the use of a particular drug

Question 22

what is a contraindication?

Answer 22

a disease of condition in which a particular drug should not be used

Question 23

what is an adverse effect?

Answer 23

an unintended effect from normal drug administration

Question 24

what is a therapeutic index?

Answer 24

quantitative measurement of the relative safety of a drug. a comparison of the amount of an agent that causes the effect to the amount that cause toxicity