Pharmacology

Question 1

What is the definition of a drug?

Answer 1

“a chemical substance of known structure which, when administered to a living organism, produces a biological effect”

Question 2

How do G protein coupled receptors work?

Answer 2

They activate a variety of signalling systems via interactions with different G proteins.
e.g. Gs activates adenyl cyclase that increases cAMP

Question 3

What active compounds have been isolated from plants and animals?

Answer 3

• morphine isolated from opium poppies
• quinine isolated from tree bark
• atropine isolated from plant used as eyedrops
• Digoxin isolated from fox glove plant, used for your heart

Question 4

Define pharmacodynamics.

Answer 4

The quantitative and qualitative study of how drugs interact with chemically sensitive sites (receptors)

Question 5

Why are most drugs in clinical use a small molecule?

Answer 5

• if smaller, more likely to enter the body and be absorbed and so reach the site of action

Question 6

What chemical formula is given for the interaction of a drug with its receptor?

Answer 6

D+R = DR

Question 7

What is the Hill-Langmuir equation and what does it show?

Answer 7

p= [D]/ [D] + Kd
It shows the proportion of receptors occupied by a drug (p)
- the longer the drug binds the more effect

Question 8

What parameter is used to measure the affinity of a drug for its receptor?

Answer 8

Kd

- the lower the Kd, the higher the affinity

Question 9

What is an agonist?

Answer 9

A chemical that bits to its target to increase the activity

Question 10

What is an antagonist?

Answer 10

A chemical that opposes the action of another chemical. This means that antagonist’s should have no action on their targets in the absence of an agonist.

Question 11

What does EC50 measure?

Answer 11

EC50 = concentration of the agonist where half of maximal possible effect occurs
pEC50 is the -log(EC50)

Question 12

What EC50 value shows a potent drug?

Answer 12

low EC50, high pEC50

Question 13

What changes does a competitive antagonist make?

Answer 13

• prevents the binding of the agonist
• ‘right shift’ on graph
  (difference between both lines is the CR)
• increase the apparent EC50

Question 14

What changes does a non- competitive antagonist make?

Answer 14

• binds at a different binding site from the agonist and prevents the effects of the agonist
• Curve shifts down
• does not change the EC50

Question 15

Define efficacy.

Answer 15

Measure of the degree to which an agonist produces a response when binding a given proportion of receptors

Question 16

What is the efficacy for a full agonist and a competitive agonist?

Answer 16

Full agonist has the efficacy of 1

Competitive agonist has efficacy of 0

Question 17

What does an allosteric modulator do?

Answer 17

• A ligand that increases or decreases the action of an agonist or antagonist
  if increases activity of the agonist it is a positive allosteric modulator
  If decreases then it is a negative allosteric modulator

Question 18

What shift on a graph is seen if there is a positive allosteric modulator presence?

Answer 18

• shift to the left

Question 19

What is the therapeutic window?

Answer 19

The window in between the minimum and maximum toxic concentration. Where we want the duration of the therapy of the drug to be. Too high = toxic. Too low = won’t work

Question 20

How do you work out the therapeutic radio?

Answer 20

TD50 / ED50
TD50 - toxic dose of a drug for 50% of the population
ED50 - minimum effective dose for 50% of the population

Question 21

What therapeutic ratio can be seen in the safest drugs?

Answer 21

a high therapeutic ratio

Question 22

What does ADME stand for?

Answer 22

Absorption - the way the drug enters the body to reach the systemic circulation
Distribution - movement of drug from systemic circulation elsewhere to the body
Metabolism - how the drug is metabolised by the enzymes in the body
Excretion - how the drug is cleared by the body

Question 23

What is ADME important for?

Answer 23

• drug development
• understanding toxicity
• establishing route of administration
• establishing drug dose
• understanding possible drug interactions

Question 24

What is the definition of Bioavailability?

Answer 24

Fraction of unchanged drug that reaches systemic circulation

Question 25

What decreases a drugs bioavailability?

Answer 25

• poorer absorption

- first pass metabolism

Question 26

What is absorption of a drug dependent on?

Answer 26

1. route of administration and the rate at which it is taken up
2. chemical nature of the compound (lipophilicity - the higher the better, charge - uncharged is faster, size - smaller is faster)
3. formulation

Question 27

What are the route of administration for drugs?

Answer 27

Intravenous (IV) - fast and 100% bioavailability but invasive with infection risk
Intramuscular IM - fast but invasive / painful and can cause local reactions (insulin)
Sublingual- fast, but only a very small amount can be absorbed so requires potent drugs
Orally / Rectally - slow, with first pass metabolism, but non invasive
Transcutaneous - only suitable for some drugs - lipophilic carriers needed to cross the skin

Question 28

What barriers do drugs have to cross?

Answer 28

• epithelial barriers

- cell membranes

Question 29

What different ways can a drug distribute itself around the body?

Answer 29

• no distribution for large drugs, stay in circulation (heparin)
• distribution through extracellular space
• distribution through total body water
• accumulation in cells (due to specific transporters that will pump it into specific cells)
• distribute to fat (can detect THC in weed for weeks due to it staying in the fats)

Question 30

What is the volume of distribution equation?

Answer 30

Vd = D/Cp
D= amount of drug (mg) and Cp = conc. of drug in the plasma (mg/L)

Question 31

What is the common method of metabolism for drugs?

Answer 31

2 phase process
Phase 1: MODIFICATION
- cytochrome P450 dependent mixed-function oxidase
- commonly causes an oxidation, reduction or hydrolysis
Phase 2: CONJUGATION
- joins the phase 1 metabolite onto another molecule in order to make it charged
- join to groups such as glutathione (GSH), glycine
- done in the liver

Question 32

What happens in an overdose situation?

Answer 32

Conjugation of NAPQI cannot happen quick enough and NAPQI accumulates. This is toxic and high conc in the liver can cause liver failure.

Question 33

What are the route for drugs and their metabolites to exit out of the body?

Answer 33

1) Renal (kidney)
2) Hepatic (liver) and hence faecal through bile
3) Other - swear, milk, breath