Drug receptor interactions

Question 1

What is Pharmacokinetics

Answer 1

It can be thought of the effect of the body on the drug- the movement of drugs in the body.

I.e. the way that the drug is distributed once it is taken and how it is absorbed.

Question 2

What is pharmacodynamics?

Answer 2

This the effect of the drugs on the body- the mechanisms of action that the drug has on the body.

Question 3

What is the definition of a drug?

Answer 3

A chemical substance that interacts with a biological system to produce a physiological effect

Question 4

What are the 4 types of drug target sites?

Answer 4

1. Receptors
2. Ion channels
3. Transport cycles
4. Enzymes

All of which are proteins

Question 5

Describe the Receptors drug target site

Answer 5

They are proteins within the cell membrane (usually- the steroid receptor can be found inside the nucleus).

They therefore have good exposure to the drugs. They are activated by NTs or hormones. They are defined by agonist or antagonist actions.

There are 4 types of receptor (look further down). The four different types of receptor are defined by their structure and their transduction systems (i.e. the way in which they carry the signal across the membrane).

Question 6

What is an agonist?

Answer 6

An agonist binds to the receptor and produces an effect within the cell.

Question 7

What is an antagonist?

Answer 7

An antagonist may bind to the same receptor, but does not produce a response, instead it blocks that receptor to a natural agonist

Question 8

What are the ‘ion channel’ drug target site?

Answer 8

They are proteins in the cell membrane- selective pores that allows transport of ions down its concentration gradient.

Question 9

what are the 2 type of ion channel target sites?

Answer 9

1. Voltage gated (e.g. VGCC)
2. Receptor-linked (e.g. nAChR)

Question 10

Explain the ion channel (nAchR)

Answer 10

nAChr- nicotinic ACH receptor (ion channel). When ach binds to the nicotinic receptor, it has a conformational change and then ion channel opens. Influx of sodium. Drugs tend to interact with the ion channel part of this mechanism.

Question 11

Give 2 examples of ion channel drug target sites

Answer 11

1. LAs- local anesthetics
2. Calcium channel blockers

Question 12

Explain, briefly, what LAs do

Answer 12

Local anesthetic blocks the influx of sodium to stop the production of action potentials– we perceive that as a numbed area

Question 13

Explain, briefly, what calcium channel blockers do

Answer 13

Used in cardiovascular stuff- good hypertensive drugs, anti-anginal drugs.

They block influx of calcium so there is relaxation of smooth muscle and dilation.

Question 14

What are the “transport systems’ drug target?

Answer 14

They are proteins which facilitate the movement of molecules and ions against their concentration gradient.

they have a high specificty for certain species only

Question 15

Give examples of the transport system

Answer 15

• Na⁺/K⁺ ATPase
• NA “uptake 1”

Question 16

Give 2 examples of drugs that use transport system drug target, and explain their mechanism briefly

Answer 16

• TCAs- Tricyclic anti-depressants. They interact with Uptake 1 of NA (noradrenaline) therefore there is an increased concentration of NA in the synaptic cleft.
• Cardiac glycosides (digoxin)- binds to the Na⁺/K⁺ ATPase and slows the transporter down. There is an increase in the intracellular Ca²⁺ (due to the increased intracellular Na⁺) and this improves the contractility of the heart.

Question 17

What are the “enzymes” drug target site?

Answer 17

They are catalytic proteins that increase the rate of reaction

Question 18

Give three pharmacological interventions to do with enzymes?

Answer 18

1. Enzyme inhibitors
2. False substrates
3. Prodrugs

Question 19

Give an example of an enzyme inhibitor

Answer 19

anticholinesterase

Question 20

Give an example of a false substrate and what it does

Answer 20

e.g. methyldopa.

Methyldopa replaces DOPA in the body which is needed to produce NA. Instead, methylNA is produced and is less effective at muscarinic receptors to innervate muscles. Therefore, the muscles relax.

Question 21

Give an example of a prodrug and how it works

Answer 21

e.g. chloral hydrate –> trichloroethanol.

Used to treat insomnia. Prodrugs are inactive until they are metabolised by the body to the active drug.

Question 22

Describe the agonist/ receptor interaction based on this picture

Answer 22

The first part of the drug-receptor interaction is the binding of the drug to the receptor.

It goes on to form the agonist-receptor complex.

There are electrostatic forces, hydrogen bonding etc. interactions between the receptor and the agonist.

Question 23

What are partial agonists?

Answer 23

Partial agonists are agonists that cannot elicit the same maximum response as the full agonists even if they have the same affinity for the receptor.

Question 24

What is the main, vital difference between agonists and partial agonists?

Answer 24

The difference between partial and full agonists is EFFICIACY.

Partial drugs can have the same affinity but reduced efficiacy

Question 25

What is the definition of affinity?

Answer 25

Strength of binding/ avidity of the drug to the receptor

Question 26

What is the definition of efficiacy?

Answer 26

The ability of a drug to elicit a response when it binds to the receptor

Question 27

Why do we not use the word SPECIFICITY when describing how well a receptor accommodates the agonist?

Answer 27

Specificity intimates that there is one to one interaction when in fact, at higher concentrations, a drug may not be specific to the same receptors at a higher concentration

Therefore, you use the term selectivity.

Question 28

Interpret and give reasons for the changes seen in these concentration-response curves

Answer 28

First graph- for the same response, there needs to be a greater concentration of the partial response agonist as opposed to the full agonist.

Second graph- if an agonist has a lower affinity, this means that it doesn’t bind to the receptor as well. There is a shift to the right. (Same shift for partial agonists).

Third graph- antagonists are drugs that have affinity for receptors, but they do not have efficacy- i.e. they do not bring about a response. There are two types of receptor antagonist:

Competitive (e.g. atropine and propranolol). It uses the same receptor as the agonist and occupies them. This essentially dilutes the receptor concentration. There is a parallel shift to the right. Competitive antagonists can be overcome by higher concentrations of the agonist. Propranolol is a widely used beta-blocker- antihypertensive and antianginal drug.

Irreversible (e.g. hexamethonium)- they have the ability to reduce the maximum response at high doses. They bind tightly to the receptor sites. They cannot be overcome even with high concentrations of the agonist.