Physiology and Pharmacology 5: Introduction to Receptors

Question 1

Main drug target molecules

Answer 1

Proteins

• Receptors
• Enzymes
• Transport proteins
• Ion channels

Nucleic acids
- DNA, RNA and the ribosome

Miscellaneous
- e.g. Antacids neutralise H+ to reduce gastric acidity

Question 2

Characteristics of enzymes as drug targets

- 2 examples, competitive and non-competitive

Answer 2

Inhibitors

• competitive or non-competitive
• reversible or irreversible
• e.g. Acetylsalicylic acid “aspirin” - cyclooxygenase (non-competitive)
• Statins e.g. simvastatin “Zocor” HMG-CoA reductase

Question 3

What are Pro-drugs? example

Answer 3

Pro-drug first requires chemical/enzymic modification before becoming active

• e.g. Angiotensin-converting-enzyme (ACE) inhibitor Enalapril is converted to the ACE inhibitor Enalaprilat by cellular esterases

Question 4

Characteristics of transporters as drug targets

give 2 similar acting examples for each action

Answer 4

Inhibitors

• Block transport
• e.g. cocaine (binds to monoamine transporters and inhibits transport of neurotransmitter)

False Substrates
- e.g. amphetamine (acts as false substrate of monoamine transporters)

Question 5

Characteristics of ion channels as drug targets

2 examples, 1 for each type of action

Answer 5

Ion channel blockers
- drug binds to channel pore affecting ion permeation

• e.g. Tetradotoxin (from poison pufferfish fugu) (voltage-gated sodium channel blocker)

Ion channel modulators

• bind to the ion channel protein to affect gating
• can have a positive or negative effect
• e.g. Gliclazide - a sulfonylurea used in the treatment of type 2 diabetes (is a modulator of ATP-sensitive potassium channels in the pancreas, results in more insulin release)

Question 6

Characteristics of receptors as drug targets

2 examples, 1 for each type of action

Answer 6

Agonists

• a ligand that binds to and activates to a receptor to produce a biological response
• have both affinity and efficacy
• drugs which act as an agonist mimics (or is) the endogenous ligand of the receptor

e. g. Noradrenaline is the natural agonist of adrenoceptor
- salbutamol acts as an agonist

Antagonist

• ligand that binds to a receptor with high affinity and prevents its activation by an agonist
• possesses affinity but no efficacy
• competitive or non-competitive
• reversible or irreversible

e.g. Beta-blockers e.g. propranol

Question 7

Characteristics of nuclear receptors and associated ligands

- give 3 examples

Answer 7

Nuclear receptors

• usually lipophilic signalling so freely traverse membranes
• e.g. steroid, thyroid, vitamin D and retinoic acid

Question 8

Characteristics of ligand-gated ion channels

- give examples

Answer 8

Sub-family of the ion channel superfamily that are regulated by the binding of a specific agonist

• e.g. acetylcholine, glutamate, GABA, glycine, 5-HT, ATP