Pharmacology

Question 1

What is pharmacology?

Answer 1

The study of the action of drugs on the function of living systems

Question 2

What is a drug

Answer 2

A chemical substance or natural product that affects the function of cells, organs, systems or the whole body

Question 3

Where do drugs come from

Answer 3

• natural products
• serendipity (accident)
• changing the structure of an existing molecule
• using an existing drug

Question 4

What are the three types of names for drugs

Answer 4

• chemical (named after the structure)
• generic (non proprietary name given to a molecule)
• proprietary (trade name)

Question 5

What is pharmacokinetics

Answer 5

What the body does to the drug

Question 6

What is pharmacodynamics

Answer 6

What the drug does to the body

Question 7

Describe the process of drugs entering the body and then getting excreted

Answer 7

Absorption, distribution, metabolism and then excretion

Question 8

What ways are drugs absorbed

Answer 8

Absorbed through the gastrointestinal transport, gastrointestinal metabolism and hepatic first pass effect

Question 9

Describe drug distribution

Answer 9

Distributed in the intravascular space, extravascular space and through protein binding

Question 10

Where are drugs metabolised

Answer 10

In the liver

Question 11

What are the routes of drug penetration into cells

Answer 11

• diffusion through the lipid membrane
• diffusion through aqueous channels
• carrier mediated transport
• pinocytosis

Question 12

What is the major route for lipophilic drugs

Answer 12

Diffusion through the lipid membrane

Question 13

What is the major route for hydrophilic drugs

Answer 13

Carrier mediated transport

Question 14

What is pinocytosis

Answer 14

Transport of insulin into the brain

Question 15

What is lipinskis rule of 5

Answer 15

• a molecular mass less than 500 daltons
• no more than 5 H- bond donors
• no more than 10 H- bond acceptors
• an octanol water partition coefficient log P no greater than 5

Question 16

Describe phase 1 of drug metabolism

Answer 16

Phase 1
Reaction - oxidation, reduction, hydrolysis
Effect - functionalisation (adding new functions), addition or unmasking of reactive group

Question 17

What is the consequence of phase 1 metabolism of a drug

Answer 17

Small decrease in lipophilicity
Slight increase in excretion
Change in pharmacological effect

Question 18

Describe phase 2 metabolism of a drug

Answer 18

Reaction
Effect - conjugation, addition of large and often charged group
Consequences - large decrease in lipophilicity, large increase in excretion, usually a decrease in pharmacological effect

Question 19

At Cmax rate of … equals rate of …

Answer 19

At cmax rate of absorption equals rate of elimination

Question 20

What are the drug effects at a cellular level

Answer 20

Drugs can have an effect on receptors, ion channels, enzymes, transporters and DNA ect

Question 21

What are the sites that drugs usually act upon

Answer 21

Many drugs mimic or block the action of endogenous molecules (eg. Hormones and neurotransmitters) they act at specific sites : receptors, ion channels, enzymes and transporters (all of which are proteins)

Question 22

How do drugs act

Answer 22

Drugs are typically small chemical molecules, they exert a chemical influence on constituents of cells to produce a pharmacological response, they get close enough to cellular constituents in order that they can interact chemically

Question 23

What are the protein targets for drug binding called

Answer 23

Receptors

Question 24

What is the direct effect of an agonist binding to a receptor

Answer 24

Ion channel opening or closing

Question 25

What are the transduction mechanisms when an agonist binds to a receptor

Answer 25

- enzyme activation/inhibition - ion channel modulation - DNA transcription

Question 26

What is the effect of an antagonist binding

Answer 26

No effect

Question 27

Why are receptors important

Answer 27

They are used for cell to cell communication

Question 28

What is the basic receptor structure

Answer 28

1) extracelllar domain (contains ligand binding sites comprised of hydrophilic amino acids) 2) transmembrane domain (anchors proteins in membrane , comprised of hydrophobic amino acids) 3) intercellular domain (interacts with effectors mechanisms compromised of hydrophilic amino acids)

Question 29

What kind of signal transduction would a ligand gated ion channel be used for

Answer 29

Very fast signal transduction (milliseconds)

Question 30

What signal a G protein coupled receptor transduce

Answer 30

A fast signal transduction (seconds)

Question 31

What signal would a kinase linked receptor be used to transduce

Answer 31

A slow signal transduction (hours)

Question 32

What signal would a nuclear receptor be used to transduce

Answer 32

Very slow signal transduction (hours to days)

Question 33

What is an agonist

Answer 33

A drug that binds to a specific site on a receptor mimics the effect of the endogenous ligand for that site

Question 34

What is an antagonist

Answer 34

A drug that binds to a specific sit on a receptor, blocks the effect of the endogenous ligand (same or different binding site as ligand)

Question 35

Agonists posses both …. and ….

Answer 35

Agonists posses both affinity and efficacy

Question 36

What is efficacy

Answer 36

Can cause a response

Question 37

Antagonists have …. but not …..

Answer 37

Antagonists posses affinity but not efficacy

Question 38

What is affinity

Answer 38

A measure of the strength of association between ligand and receptor

Question 39

What is pharmacological variability

Answer 39

Drug response is not always the same, different people react to drugs differently due to age, sex ect

Question 40

What is general anaesthetic

Answer 40

- sedates entire body - loss of consciousness Block presynaptic calcium entry therefore no neurotransmitter release. Increases post synaptic hyperpolarisation (Cl- influx or K+ efflux)

Question 41

What is local anaesthetic

Answer 41

- sedates localised area - no loss of consciousness Block conduction axonal Na+ entry Block sodium channels

Question 42

Why are esters used rather than amides for short term use anaesthetic

Answer 42

Esters are metabolised quickly which means they have a shorter effect than amides, amides have a longer half life because they are metabolised in the liver therefore have a longer effect

Question 43

What are do anaesthetic drugs generally consist of

Answer 43

Typically weak bases

Question 44

What are the three states that sodium channels can exist in

Answer 44

Resting, open and inactivated

Question 45

Describe the mechanism of action of local anaesthetics

Answer 45

- LAs bind to a target site on the intercellular side of the Na+ channel - LAs prevents sodium influx > prevents depolarisation > prevents action potential propagation > prevents perception of pain - LAs prevents Na+ influx in 2 ways, both blocks channel and stabilises it in its inactivated conformation Causes reversible block of nerve conduction

Question 46

To be effective LAs need to:

Answer 46

1) Diffuse from site of administration, across the nerve cell membrane to the intercellular side 2) Bind to LA target site Their ability to do this is related to their chemical structure

Question 47

Describe ester linked anaesthetics

Answer 47

Rapidly metabolised by tissue and plasma cholinesterase Lasts <3mins

Question 48

Describe amide linked anaesthetics

Answer 48

Primarily metabolised slowly in the liver last about 1-3 hours

Question 49

What is the use of topical anaesthetics

Answer 49

They affect mucous membranes only, not effective on the skin

Question 50

What is potency of a drug

Answer 50

A measure of the dose (or concentration) of a drug at which it is most effective A potent drug is one that is effective in low doses

Question 51

What does it mean if a drug is selective

Answer 51

A drug is selective if it works on one receptor but not on other