Principles of Pharmacology

Question 1

Define pharmacodynamics

Answer 1

The effects of a DRUG on the body. This includes

• targets for drug action
• how drugs act at the target
• how the drug produces an action within a cell

Question 2

Define pharmacokinetics

Answer 2

what the BODY does to a drug. This includes absorption, distribution, metabolism and excretion

Question 3

Why is the study of pharmacodynamics important?

Answer 3

It allows us to determine the appropriate dose range for patients and compare the effectiveness and safety of one drug to another

Question 4

Why is the study of pharmacokinetics important?

Answer 4

It allowscis to design and optimise treatment regimens for individuals e.g. treatment duration & frequency of drug admission

Question 5

What are the 2 methods of drug interactions with targets?

Answer 5

1. Shape- this determines the binding abilities of the drug

2. Charge distribution- this determines the type of bonds that holds the drug to the target

Question 6

List other factors that affect drug interactions with targets

Answer 6

• hydrophobicity
• ionisation of drug (pKa)
• confirmation of target
• stereochemistry of drug molecule

Question 7

What are the main target proteins?

Answer 7

1. Receptors: are the targets for endogenous transmitters e.g. hormones and neurotransmitters
2. Ion channels: pores which span membranes to allow the selective passage of ions
3. Enzymes: either inhibit or act as a false substrate
4. Carriers: transport ions and smll organic molecules or inhibit transport

Question 8

Which drugs act by virtue of their physio-chemical properties?

Answer 8

1. Antidotes e.g. acetylcysteine to treat paracetamol overdose- simply to do with molecule shape
2. Antacids e.g. aluminium hydroxide- neutralises acidic content of stomach
3. Laxatives e.g. lactulose (osmotic laxative)

Question 9

Differentiate between an agonist and antagonist

Answer 9

An agonist is a ligand that mimics the action of chemical messengers to elicit a cellular response , while an antagonist blocks the action of kf chemical messengers and thus the response

Question 10

Give an example of an agonist and antagonist respectively

Answer 10

Histamine acts as an agonist at the H1 receptor in smooth muscle to increase blood flow

Terfenadine acts as an antagonist at the H1 receptor in smooth muscle to decrease local blood flow

Question 11

Name the 4 receptor types which respond to drugs

Answer 11

1. Ligand gated: channel linked receptors that require agonist to open channel e.g. nicotinic ACh
2. Voltage gated: not linked to receptors, on steady require change in electrical charge across a membrane to open/close e.g. Na+
3. G protein couple (metabotropic): largest family of receptors formed of a single polypetide chain and 7 transmembrane helices. Consists of alpha, beta and gamma subunits.
4. Intracellular
   a- Kinase linked: large extracellular ligand binding domain connected to Intracellular domain by single membrane spanning helix —> dimersation —> autophosphorylation

b- Nuclear receptors: family of 48 soluble receptors. Has class I- located in cytoplasm, forms homodimers, ligands are endocrine (sterioids, hormones) & class II- present in nucleus, forms heterodimers, ligand are lipids
Binding to hormone response elements initiates gene transcription changes (+/-)

Question 12

What are orthosteric sites?

Answer 12

The normal binding sites for endogenous products, turning processes on/off

Question 13

What are functions of the alpha subunits?

Answer 13

Gs (stimulatory): activates adenylyl cyclase & Ca2+ channels

Gi (inhibitory): inhibits adenyl cyclase and actives K+ channels

Gg: activates phospholipase C

This plays an important role in adrenoreceptors as receptor type dictates the effect in the body

Question 14

What are the 2 types of dose response curves (or concentration effect curve)?

Answer 14

1. Graded: response of a particular system (INDIVIDUAL) e.g. tissue, animal or patient. Measured against [agonist]
2. Quantal: drug doses, used to produce a specified response determined in each memeber of a population. Used for population based research usually

Base 10 logs are used for curves so there is a tenfold increase from one unit to the next

Question 15

What do dose response curves allow?

Answer 15

• the estimation of emax which is used to deduce drug efficacy
• the estimation of concentration or dose required to produce 50% of maximal response (EC50/ED50) which can be used to work out drug potency

Question 16

explain drug affinity

Answer 16

The strength with which an agonist/drug binds to a receptor. It’s how easily does the drug bind/ fall off

• it is calculated as the rate of association of agonist with receptor/ the rate of AR complex dissociation
• a high affinity drug has a much greater tendency to bind to the receptor relative to its dissociation

Question 17

Explain efficacy

Answer 17

How easily the drug can become active

• is determined by the nature of the receptor-effector system
• refers to the maximum effect an agonist can produce regardless of dose

Question 18

Explain Kd

Answer 18

It is the equilibrium dissociation constant and can be used to identify receptors.

• is a physiochemical constant
• is the same for a given receptor and drug combo in any tissue/ soecies thus can be used to identify an unknown receptor
• can be used to quantitatively compare the affinity of different drugs on the same receptor

Question 19

What is the relationship between Kd and the concentration curve?

Answer 19

Kd maps over the EC50 so curve can tells us about affinity of the drug receptor complex
- the less of the drug required, the lower the Kd value, the greater the affinity, the tighter the ligand receptor interaction

Question 20

Explain ‘potency’

Answer 20

How much of the drug is needed to bind to create the desired effect (=50% Emax)

• true affinity can only be determined by binding dose relationships
• lower the EC50, the greater the potency (agonists with high potency tend to have a high affinity so graph is further to the left)

Question 21

What factors is potency dependent on?

Answer 21

• drug affinity
• drug efficacy
• receptor density
• efficiency of stimulus- response mechanisms used

Question 22

Outline the differences between a full agonist (high efficacy) and partial agonist (low efficacy)

Answer 22

• FA produces a max response while occupying only a small % of receptors available, while PA is unable to even when occupying all available receptors
• with FA the