L4 - Drug Target Pharmacodynamics - Part 1

Question 1

what is a drug

Answer 1

• drugs are molecules that interact with a biological system to produce a biological response

Question 2

what are the characteristics of drugs?

Answer 2

• most are small molecules with MWs < 600 and not endogenous
• more ‘biologics’ are now entering the clinic
  
  • e.g. antibodies and proteins as therapeutic agent
• no drug is safe
  
  • efficacy (ability to produce desired result) verus toxicity

Question 3

endogenous

Answer 3

not naturally occuring in the organism

Question 4

what is drug safety dependant on

Answer 4

• its therapeutic index
• varies for all drugs
• administering the right dose is essential

Question 5

what is the therapeutic window

Answer 5

• the difference between the toxic response and desired clinical response

Question 6

why are drugs administered

Answer 6

• achieve a biological response that alleviates the symptoms or cause of an illness

Question 7

wjat causes illness/symptoms

Answer 7

a biological process

Question 8

what is usually a drug target at a molecular level

Answer 8

• usually a biomacromecules involved in the biological process
• e.g. receptor, enzyme, ion channel)

Question 9

how do drugs taken orally go to intended target

Answer 9

• absorbtion from small intenstine is a dynamic process
  
  • rate of uptake needs to be greater
• passes through the hepatic protal vein
  
  • first pass effect - some drug metabolised
  • the rest of the drug is said to be bioavailabel
• passes through the circulation-tissue barrier

Question 10

Cyclo-oxygenase (COX)

why is it a target for a drug

how does it work

Answer 10

• prostaglandins (PGs) are part of the inflammatory response, and their systhesis is increased at the site of inflammation
• COX initiates the PG synthesis cascade by catalysing the cyclisation and oxidation of its substrate arachidonic acid (AA)
• non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and flurbiprofen are competitive inhibitors of COX
  
  • they bind to the COX catalytic site, which prevents AA from binding and being converted to PGs
• inflammation is reduced and PG levels go down

Question 11

WHat is the side effect of using non-steroidal anti0inflammatory drugs?

Answer 11

• high pg levels increase mucosal thickness of the stomach wall, which protects it from degradation by acid
• non-specific inhibition of COX here reduces PG levels, making the stomach susceptible to ulceration

Question 12

how does salbutimol work?

Answer 12

• activation of β₂ adrenoreceptors in bronchial smooth muscle by adreanaline and noradreanaline dilates the airways
• drugs like salbutamol are agonists for this receptor
  
  • they mimic the ffect of the natural ligand and induce the same response
• bronchial smooth muscle relaxes and asthmatic patients can breathe more easily
• conc of salbutamol must be maintained to keep stimulating the airway
  
  • however, providing the cause of the asthma attack is no longer present, repeated dosing may not be required