Pharmacodynamics III - Drug action and dose-response relationship

Question 1

What does metoprolol do?

Answer 1

It is a drug taken to decrease number of anginal episodes.

Question 2

How is angina treated?

Answer 2

Lifestyle changes (smoking, weight loss, healthier diet)

Medications (relieve intensity of angina, reduce changes of heart attack, relieve intensity of angina)

Surgery (to clear blocked arteries)

Question 3

Why is nitroglycerin used for treatment of angina?

Answer 3

Causes dilation of coronary arteries

Question 4

How often must metropolol be taken?

Answer 4

Regularly as a prophylactic measure even when there are no angina symptoms.

Question 5

When should a drug be taken?

Answer 5

Some drugs are taken either prophylactically (like metoprolol) or as needed (like nitroglycerin)

Question 6

When must drugs like nitroglycerin be taken?

Answer 6

During an attack of angina or before activities that usually cause angina

Question 7

How much metoprolol must be taken to effectively reduce angina attack frequency?

Answer 7

100 - 200 mg

Question 8

What is potency?

Answer 8

Dose required to produced a desired effect

Question 9

How important is potency in selecting a drug?

Answer 9

Potency is rarely a determining factor. Potency is important when there is a limited capacity to administer a large amount of drug as is the case in transdermal patches (or anaesthetic darts to immobilise elephants)

Question 10

What does effectiveness of a drug mean?

Answer 10

The maximum level of effect is higher in more effective drugs.

Question 11

How important is effectiveness in selecting a drug?

Answer 11

It is very important in choice of drug

Question 12

How does metoprolol work?

Answer 12

Binds to beta1-adrenoceptor which is a GPCR normally activated by adrenaline/noradrenaline and is highly expressed by cardiac cells.

Question 13

How many times does the beta1-receptor pass through membrane?

Answer 13

7 times

Question 14

What kind of antagonist is metoprolol?

Answer 14

A competitive antagonist

Question 15

What type of medication is metoprolol?

Answer 15

A beta blocker

Question 16

What other receptors does metoprolol bind to?

Answer 16

beta2-adrenoceptors

Question 17

Which receptors does metoprolol have a higher affinity for?

Answer 17

Beta1 > beta2 (6 fold higher affinity)

Question 18

What’s the impact of metoprolol having a higher affinity for beta1 than beta2 adrenoceptors?

Answer 18

At low concentrations beta1 binding is fine and beta2 is minimally bound. (selective binding to beta1 and hardly any binding to beta2)

At higher concentrations beta2 is bound sufficiently to have its effect blocked resulting in severe effects in people with asthma and other disorders of bronchi.

Question 19

Example of enzyme inhibitors?

Answer 19

Aspirin which binds to COX to prevent production of pain causing molecules.

Question 20

What are the methods of enzyme binding by drugs?

Answer 20

Drugs that bind and inhibit enzymes

Drugs that act as false substrates and are converted to different products

Question 21

What kind of drug is imatinib?

Answer 21

A drug that targets enzyme binding (BCR-Abl is a kinase expressed by leukaemic cells)

Question 22

What is a common drug that targets transporters?

Answer 22

The anti-depressant drug Fluoxetine (Prozac) which inhibits reuptake of serotonin into neurons.

Question 23

What does lidocaine do?

Answer 23

It binds to and blocks voltage-gated sodium channels.

Question 24

What makes up the voltage sensor of sodium channels in neurons?

Answer 24

4 positively charged ions.

Question 25

How does the sodium channel work?

Answer 25

Repulsion of voltage sensor drives it upwards which opens the sodium channel.

Inactivation gate closes the channel after it opens due to electrostatic repulsion form ions passing through the voltage gated ion channel.

Question 26

How does lidocaine work?

Answer 26

it contains a protonated amine group and an aromatic group linked by linker group.

Lidocaine binds to activation gate and the protonated amine group repulses the ions that enter the cell and the hydrophobic aromatic group stabilizes it within the channel.

Question 27

What do benzodiazapenes do?

Answer 27

They act as positive allosteric modulators that increase GABA receptor affinity to enhance opening of GABA-activated chloride channels.

This results in a decrease in anxiety.