essential pharmacology

Question 1

what can hydrophobic/ lipophilic signalling molecules do? give 2 examples:

Answer 1

dissolve through the lipid bilayer of the plasma membranes and bind to intracellular receptors.

e.g.

1- Nitric Oxide (NO)

• Binds to soluble guanylyl cyclase in the cytosol
• Generates cGMP as 2nd messenger to regulate cell activity

2- Steroid hormones

• Transcription factor receptor → regulates transcription in the nucleus

Question 2

what is signal transduction?

Answer 2

the process of turning a chemical signal into an appropriate response.

This could be changes in: (depending on the receptor)

• Membrane permeability
• Metabolism
• Secretory activity
• Contractile activity
• Rate of proliferation or differentiation

Question 3

how does intercellular communication occur?

Answer 3

through chemical signals (e.g. hormones, neurotransmitters) released from one cell that produce a response only in the cells that express the right receptors for it [specificity]

Different receptor subtypes can evoke different responses in other cells.

Question 4

what do hydrophilic/ lipophobic signalling molecules do?

Answer 4

bind to receptors on the cell surface to create an intracellular response.

Question 5

what are the 4 types of cell surface receptors?

Answer 5

Receptor-channels
- Ligand-gated ion channels
- Known as Ionotropic receptors e.g. nicotinic ACh receptors

G protein-coupled receptors (GPCRs)
- Known as Metabotropic receptors - use a middleman, the G protein

Receptor-enzymes
- Receptors with intrinsic enzymic activity, e.g. insulin receptors,
- Bound to an enzyme, e.g. cytokine receptors

Integrin receptors
- Receptors that interact with the cytoskeleton

Question 6

what 2 things do G protein-coupled receptors couple to?

Answer 6

Ion channels
(affects membrane potential and firing of action potentials)

e.g. slow EPSPs & IPSPs → metabotropic receptors

Enzymes e.g. adenylyl cyclase
- Converts ATP to cAMP as 2nd messenger

• cAMP regulates protein kinase A (PKA) activity → phosphorylation of target proteins → cellular response

Question 6

give an example of a g protein-coupled; receptor

Answer 6

e.g. phospholipase C (PLC)

• PLC converts membrane phospholipids to IP3 and DAG as 2nd messengers
• IP3 releases Ca2+ and DAG regulates protein kinase C (PKC) activity

(both Ca2+ & DAG regulate PKC - double whammy)

• PKC phosphorylates target proteins and change their activity

Question 7

what are the effects of Ca2+?

Answer 7

Directly affects target protein e.g. Protein Kinase C (PKC)

Ca2+ - Calmodulin complex → activates MLCK for phosphorylation of myosin neck region ‘RLC’ in Smooth Muscles

Ca2+ - Troponin complex → pulls tropomyosin off the binding site to allow cross-bridges in Skeletal Muscles

Question 7

what are the sources of Ca2+?

Answer 7

IP3 or Ca2+-stimulated release from internal stores
e.g. ER (in other cells) / SR (in skeletal cells)

• Outside of the cell via voltage/ligand-gated Ca2+ channels
• Inhibition of Ca2+ transport out of the cell

Question 8

what are the 2 agents of pharmacology?

Answer 8

Endogenous agents made by the body i.e. hormones/neurotransmitters

Exogenous agents e.g. drugs

Question 9

what is a drug? what are the sources?

Answer 9

A drug is any chemical agent that affects a biological system.

Sources:

– Natural products from plants

– Synthetic drugs generated by the pharmaceutical industry

– Biotechnology using living systems to make therapeutic agents

Question 10

give 6 examples of 6 receptors:

Answer 10

cell surface receptors e.g. b-adrenergic receptors

Intracellular receptors e.g. steroid receptors

Ion channels e.g. tetrodotoxin (TTX) block Na+ channels

Carriers e.g. ouabain inhibits Na+/K+-ATPase

Enzymes e.g. aspirin inhibit cyclo-oxygenase

Nucleic acids e.g. tumour promoters & DNA

Question 11

How does the amount of ligand affect the drug-receptor interactions?

Answer 11

A small amount of ligand → small response

A large amount of ligand → larger response

Maximum amount of ligand → maximum (saturated) response

• Nothing happens anymore if you add more ligands.

Question 12

how does the concentration of EC50 affect the affinity?

Answer 12

EC50 is inversely proportional to the affinity between a drug and a receptor.

Lower EC50 indicates higher affinity (left shift on the x-axis)

Higher EC50 indicates lower affinity (right shift on the x-axis)

Question 13

What is the s shape of the agonist concentration-response curve?

Answer 13

sigmoid curve

Question 13

what is the function of agonists and antagonists?

Answer 13

Agonists mimic the normal effect of a receptor.

Antagonists block the normal action of a receptor

Question 14

what receptor subtypes does adrenaline act on?

Answer 14

e.g. adrenaline – the endogenous agonist activates all adrenoceptors, a1, a2, b1, b2 - the “master key”

Question 15

what are selective agonists and antagonists? give examples:

Answer 15

Selective agonists are drugs that activate only some of those receptors.

– e.g. salbutamol - a b2-agonist (asthma)

Selective antagonists are drugs that block only some of those receptors.

– e.g. propranolol - a b1 and b2-antagonist
- Based on structure-activity relationships
- arrythmias