integrative lecture

Question 1

what is Myasthenia Gravis?

Answer 1

an autoimmune disease in which the body produces antibodies to nAChRs. characterised by weakness and fatigue of muscles, worsened by activity

Question 2

what is the treatment for MG?

Answer 2

acetylcholineesterase inhibitors to increase level of acetylcholine at the neuromuscular junction

Question 3

outline stimulation of the neuromuscular junction

Answer 3

1) action potential arrives in motor nerve 2) depolarisation opens VG-Ca2+ channels 3) increase in calcium causes fusion of acetylcholine vesicles 4) ACh diffuses across the synapse 5) ACh acts at nicotinic acetylcholine receptors, causing depolarisation

Question 4

what is physostigmatine?

Answer 4

an acetylcholinesterase inhibitor identified first as a treatment for curare poisoning

Question 5

when are anti-thrombotic drugs used?

Answer 5

after a heart attack, stroke, coronary stent, peripheral arterial disease

Question 6

what is P2Y12?

Answer 6

a GPCR expressed on platelets and activated by ADP released upon cellular injury

Question 7

what is clopidogrel?

Answer 7

a prodrug that is activated when processed by P450 in the liver. binds irreversibly to P2Y12, stopping activation. long half life (4 days)

Question 8

what is Ticagrelor?

Answer 8

second generation P2Y12 antagonist, half life 7-8.5hrs

Question 9

how does RTK overexpression result in cancer?

Answer 9

overexpression of EGFR leads to high basal activity and: glioblastoma, colorectal cancer, head and neck squamous cell carcinoma, breast, renal, ovarian, bladder, pancreatic cancers

Question 10

give an example of an RTK inhibitor

Answer 10

gefitinib is a selective inhibitor of EGFR tyrosine kinase domain. it works by sitting in the substrate binding site, having the same effect as the activation loop of RTK

Question 11

what is diabetic macular oedema?

Answer 11

blood vessel leakage in eye that occurs in long-term uncontrolled diabetes. VEGF + Ang2 are growth factors produced to excess in DME

Question 12

what are the treatments for DME?

Answer 12

RTK inhibitors, antireceptor antibodies such as ramucirumab, antiligand antibodies, VEGF-TRAP prevents VEGF access to receptor

Question 13

what is a ligand trap/decoy receptor?

Answer 13

natural extracellular domain for the ligand , preventing it from binding