Lecture 29 - Introduction to Drugs Flashcards
What is the definition of a drug?
What isn’t a drug?
A chemical compound of known structure that produces a biological effect.
It is no herbal remedies, or dietary requirements
Which neurotransmitters act on the cardivascular system?
Which receptors?
NA and Ad
alpha and beta adrenoceptors
What is the scientific basis of the action of drugs?
Molecular pharmacology Cell and tissue physiology Organ pharmacology Whole body Population
Give an example of the scientific basis of drugs
Thiazide diuretics
- Blocks Na+/Cl- transporter
- Decrease in Na+/Cl- reabsorption
- Increased excretion from kidney
- Lower blood volume and BP
- K+ loss, hyperglycaemia, gout
What is pharmacodynamics?
Effect of a drug on the body
What is pharmacokinetics?
What the body does to the drug
What are the generalised targets of drugs?
- Receptors
- Enzymes
- Ion channels / transporters
- Gene transcription / translation
Where are the generalised location of receptors?
- Cell surface
- Cytosol
- Nucleus
What are the types of cell surface receptors?
- GPCR
- Ion channels
- Tyrosine-Kinase linked
What are the two ways that two cells can interact?
Give examples of each
1/ Release of molecules
- hormones
2/ Membrane bound molecules
- immune system
How can such a small molecule bring about a response in a cell?
Amplification
Describe the generalised process of amplification
- One ligand binds to one receptor
- Receptor activates many second messengers
and so on
Describe a drug-receptor interaction that takes in the order of milliseconds to elicit a response
ACh - nAChR
At motor endplate
Describe a drug-receptor interaction that takes in the order of seconds to elicit a response
NA - Adrenoceptors
Describe a drug-receptor interaction that takes in the order of minutes to elicit a response
Insulin - IR
Describe a drug-receptor interaction that takes in the order of hours to elicit a response
Cortisol - Glucocorticoid receptor
What type of receptor is the nAChR?
Ion channel
What type of receptor is the mAChR?
GPCR
What type of receptor is the insulin receptor?
Receptor tyrosine kinase
What type of receptor are adrenoceptors?
GPCR
What is the effect of d-Turbocurarine?
Blocks Na+ channels
No action potential conductance
What is the structure of GPCR?
Receptor: 7TM (heptahelical) Binding domain extracellularly Linked to G-protein: alpha, beta gamma subunits GDP
What is a drug that targets AChE?
What does it then do?
Physostigmine
It is an antagonists - prevents the breakdown of ACh
What is a drug that targets cyclo-oxygenase?
Describe what happens when it is taken
Aspirin
Inhibits the production of inflammatory prostaglandins
What is a drug that targets the bcr-abl fusion protein?
What does the drug do?
Imatinib
Blocks the kinsase action of the fusion protein
Describe the function of receptor tyrosine kinases
- Ligands bind
- Subunits dimerise
- Auto-phosphorylation
- Tyrosine residue is phosphorylated
- Kinase property of the receptor is activated
Give an example of a nuclear hormone receptor target
Cortisol - GR
Describe the action of cortisol
- Diffuses through membrane
- Binds to GR in cytoplasm, chaperon dissociates
- GR + cortisol move to the nucleus
- Binds to DNA
- Change in gene expression
What type of hormone is cortisol?
Steroid
How is chemical signalling controlled?
Give an example of each
1/ Breakdown - ACh 2/ Reuptake - NA 3/ Metabolism, Negative feedback - Insulin - Cortisol
Describe the regulation of NA
Once it has acted on the receptors, it is taken back up by the pre-synaptic cell
What is the mechanism of action of cocaine in the body?
Blocks the reuptake of noradrenaline and dopamine
Describe the regulation of insulin in the body
Controlled by negative feedback
- Glucose in the blood
- Increased ATP in cells
- K+ channels blocked
- Depolarisation
- Release of insulin
Describe the regulation of cortisol
- Hypothalamus release CRF
- CRF leads to release of ACTH from the pituitary
- ACTH releases cortisol from the adrenal gland
- Cortisol feeds back negatively on the hypothalamus
What is ACTH?
Adrenocorticotrophic hormone
What is CRF?
Corticotropin releasing factor