Unit 11 PBL drugs

Question 1

Describe the MOA baclofen

Answer 1

Skeletal muscle relaxant
Small molecule
Activity = GABA agonist
Target = GABA B receptor

Physiology:
Activates GABA B receptor
Inhibits adenylate cyclase
Activates PLA2
Inhibits Ca2+ volted gated channels
Activated K+ conductance channels so hyper polarisation of nerve terminal
Inhibits monosynaptic + polysynaptic reflexes

Question 2

Describe the MOA diazepam

Answer 2

Benzodiazepine
Small molecule

Target = GABA a receptor ( Cl- volted gated channel)
Activity = Positive allosteric modulator 

Enhances binding of GABA to GABAa receptors
Increases opening of Cl- channels
Hyperpolarisation
Inhibits neuronal firing and AP generation

Question 3

Describe the MOA of sulfalazine

Answer 3

DMARD
Small molecule
Inactive pro drug made of 5-ASA + sulfapyridine joined by an azo bond to prevent absorption in upper GI tract

Colonic bacteria have azoreductase enzyme to break azo bond and active metabolites are released = 5-ASA + SP

Activity = Inhibitor
Target = COX-1, COX-2, LOX
- Inhibits prostaglandin synthesis
- Inhibits arachidonic acid metabolism -> leukotrienes
- Blocks NFKbeta so less pro inflammatory cytokines

Question 4

Describe MOA paracetomal

Answer 4

Atypical NSAID

Indirect inhibitor

Question 5

Describe the MOA of methotrexate

Answer 5

small molecule
Binds to enzymes involved in nucleotide synthesis
Prevents cell division
Anti inflammatory effects ( stimulation of adenosine receptors)
Methotrexate converted by methotrexate polyglutamate

• Binds to DHFR + AIRCART to inhibit their function
• Prevents cell division

Methotrexate inhibits AIRCART, leading to accumulation of AIRCART ribonucleotide
Accumulation of ATP + adenosine
Stimulation of adenosine receptors -> anti inflammatory

Question 6

Describe the MOA of hydroxycholorquine

Answer 6

Small molecule , antimarial drug
Targets = DNA, TLR 7 + TLR9, ACE enzyme
Accumulates in organelles and increases their pH
Inhibits antigen processing by preventing MHCII dimerization
recycling of MHCII complexes so only those with high affinity are near surface
Self peptides with low affinity so prevents presentation of self peptides to T cells
Inhibit TNF + IL-1 by TLR inhibition

Question 7

Describe MOA paracetomal

Answer 7

Atypical NSAID
Indirect inhibitor
Targets = COX-1,COX-2,COX-3

Question 8

Describe the MOA heparin

Answer 8

Small molecule released naturally by mast cells
Synthetic version = unfractionated mix

Target = Anti thrombin II
Activity = potentiator
Heparin binds to anti thrombin II and increases the inactivation of factor Xa, IIa and can also inactive factor IX, XI, XII and plasmin

Target = coagulation factor X 
activity = inhibitor 
inhibits conversion of pro thrombin -> thrombin
- prevents platelet activation 
- prevents coagulation cascade
- prevents fibrinogen -> fibrin