Pharmacology 2

Question 1

What is affinity?

Answer 1

How well a drug is bound to a receptor. A higher affinity means it is less easily removed when bound.

Question 2

What is efficacy?

Answer 2

Relative ability of the drug to produce a maximum intended effect when bound to the receptor.

Question 3

What is potency?

Answer 3

Relates to the dosage of the drug - what dose of the drug is needed to produce a biological effect.

Question 4

What is an agonist? What are the different types?

Answer 4

Agonist - mimics a natural chemical and so binds to a receptor and stimulates it to have a cellular response.

Partial agonist - has a partial affinity and partial efficacy. Works on the same receptor as a natural chemical but does not produce the maximum response.

Inverse agonist - has a high affinity and high efficacy. The bind to the same receptor but produce the opposite response.

Question 5

What is an antagonist? What are the different types?

Answer 5

Bind to the same receptor as an agonist and so blocks them. This binding however does not stimulate the cellular response. It has a high affinity but no efficacy. For example domperidone.

Competitive antagonist:
Bind to the same receptor but does not active it
Non-competitive antagonist:
Binds to a different site (allosteric) on the receptor preventing binding to the receptor

Question 6

Give different types of drug receptors.

Answer 6

1. G-protein coupled receptor:
   Have a 7 transmembrane domain. The drug binds to the extracellular site of the receptor. This cause the G-protein to activate and therefore use its GTPase activity to convert GDP to GTP. A subunit dissociates and activates a effector enzyme resulting in the production of a secondary messenger.
2. Receptor Tyrosine Kinases:
   Binding of the drug causes the receptor to dimerise and use its intrinsic catalytic activity to phosphorylase enzymes activating them.
3. Ligand gated receptors:
   Binding of the drug causes the channel protein to open. Made up of a 5 transmembrane domain (2 alpha, beta, gamma and a sigma). This facilities ion movement.
4. Nuclear receptors:
   The drug is lipid soluble so it can move across the plasma membrane and bind to nuclear receptors and have an effect directly on DNA; thereby acting as a transcription factor.

Question 7

What is a secondary messenger?

Answer 7

A transiently produced molecule that carries the message inside the cell to target organelles and initiates a cascade of reactions.

Question 8

Name common neurotransmitters, their function and disorders caused by imbalances.

Answer 8

Noradrenaline - important in alertness, mood and increasing heart rate. Imbalances can cause depression in low doses and insomnia in high doses.

Acetylcholine - Important in neuromuscular junctions, learning and memory. Imbalances cab cause Alzheimers in low doses.

Serotonin - Important in mood, sleep, hunger and arousal. Low levels can cause depression.

GABA - Major inhibitory neurotransmitter. Low levels cause anxiety.

Dopamine - Influences movement, attention and emotion. Low levels can cause Parkinson’s disease and high levels can cause schizophrenia.

Question 9

What is EC50?

Answer 9

The concentration of a drug that will result in 50% of the maximal response.

Question 10

What is receptor occupancy assays?

Answer 10

Receptor occupancy (RO) assays are designed to quantify the binding of drugs to their targets on the cell surface and are frequently used to generate pharmacodynamic (PD) biomarker data in nonclinical and clinical studies of biopharmaceuticals.

Question 11

What is the Kd?

Answer 11

Binding affinity is typically measured and reported by the equilibrium dissociation constant (KD), which is used to evaluate and rank order strengths of bimolecular interactions. The smaller the KD value, the greater the binding affinity of the ligand for its target.

KD = [ligand][receptor]/[ligand receptor complex]

ligand + receptor ⇌ligand receptor complex

Question 12

What is therapeutic index? What is the certain safety factor?

Answer 12

Therapeutic index: is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.

Certain safety factor:is an aspect of the dose–response relationship and is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population (LD1/ED99).

Question 13

What receptor is acted upon by Salbutamol?

Answer 13

Salbutamol is short-acting, selective beta-2-adrenergic receptor agonist used in the treatment of asthma and COPD (Chronic obstructive pulmonary disease).

Question 14

What receptor acted upon by propanolol?

Answer 14

Propanolol is a non-selective beta blocker which works by blocking beta-adrenergic receptor. It is used to prevent migraines and prevent further heart problems in those with angina or previous heart attacks.

Question 15

What receptor is acted upon by Atenolol?

Answer 15

Atenolol is used to treat high blood pressure and angina, and to reduce heart attack risk. Atenolol is a beta blocker - it blocks the beta adrenergic receptor.

Question 16

How do NSAIDs work?

Answer 16

NSAID - Non-steroid anti-inflammatory drugs. NSAIDs are inhibit cyclo-oxygenease enzymes. these COX enzymes result in the production of prostaglandins - which are inflammatory molecules. COX1 produces prostaglandins used in protecting stomach mucosa, protecting renal function and aiding platelet aggregation. COX2 produces inflammatory molecules.

Question 17

Give an example of NSAIDs.

Answer 17

• Aspirin
• Ibuprofen
• Naproxen

Question 18

How do ACE Inhibitors work?

Answer 18

Angiotensin-Converting Enzyme, ACE, inhibitors, inhibit the enzyme ACE.. As a result angiotensin I was not converted to angiotensin II. Angiotensin II leads to increased blood pressure as it causes vasoconstriction and results in the secretion of aldosterone. Due to reduced angiotensin II, ACE inhibitors can therefore be used in the treatment of high blood pressure.

Question 19

Give examples of calcium channel blockers. What are they used to treat?

Answer 19

Dihydropyridine: Target smooth muscle away from the heart. side effects are more generalised, and so are more commonly used. Used in the treatment of hypertension.
An example of this included Amoldipine

Phenylalkylamines: Selectively inhibit channels in the myocardium and are less efficient as vasodilators. They are used in the treatment of arrhythmia, cluster headaches and hypertension.
An example included Diltiazem.

Benzothrazepine: Has both cardiac depressive and vasodilator actions. Used in the treatment of angina.
An example includes Verapamil.

Question 20

How do local anaesthetics work?

Answer 20

Cause the depression of excitation in nerve endings or inhibit conduction processes in peripheral nerves. They do this by moving to the inside of the cell then binding to the ‘sodium channel’ and so blocking the influx of sodium ions.

Question 21

What is the structure of a local anaesthetic?

Answer 21

A benzene ring followed by either an amide or an ester. This is then followed by a hydrophilic tail (a quaternary amine)

Question 22

What is the main differences between amide and ester local anaesthetics?

Answer 22

Amide anaesthetics are more stable than ester anaesthetics. Hypersensitivity reactions are rare compared to that in amide anaesthetics. Esters however are rapidly hydrolysed and broken down to produce PABA (para-amino benzoic acid) which are associated with allergic reactions and hypersensitivity. The ester linkage is more easily broken down and since the ester is less stable it cannot be stored for as long. Esters are broken down by plasma esterases. Amides are broken down by amidases.