ion channel modulators, NO and H2S

Question 1

nifedipine

Answer 1

• calcium channel blocker (L-type voltage sensitive)
• treats hypertension and angina
• relaxes the muscles of the heart and blood vessels

Question 2

amiloride

Answer 2

inhibits renal epithelial Na+ channels

treat hypertension and heart faliure

Question 3

phenytoin

Answer 3

modulates voltage sensitive Na+ channels

treats siezures

Question 4

ethosuximide

Answer 4

inhibits T-type calcium channels in thalamic neurones = treats siezures

Question 5

nicorandil

Answer 5

opens ATP sensitive K+ channels

treatment for diabetes

Question 6

ion channel modulators

Answer 6

stick to an ion channel and open/close it - they don’t act on a particular receptor

Question 7

K+ channel openers

Answer 7

nicorandil and minoxidil

Question 8

K+ channel blockers

Answer 8

glimepride

Question 9

what does nicorandil do

Answer 9

stimulates production of cGMP which stimulates PKG - reduces Rho kinase activity - less calcium sensitivity

PKG - acts of K+ channels - more efflux and hyper polarisation - relaxation

Question 10

the effect of nicorandil as a vasodilator is mainly attributed to

Answer 10

it nitrate properties

Question 11

what does glimepride do

Answer 11

It lowers blood sugar by stimulating the release of insulin by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors

Question 12

what was a side effect of minodixidil

Answer 12

increase hair growth

Question 13

how is glimpride metabolised

Answer 13

First, the medication is metabolized to M1 metabolite by CYP2C9. M1 possesses about ​1⁄3 of pharmacological activity of glimepiride, yet it is unknown if this results in clinically meaningful effect on blood glucose. M1 is further metabolized to M2 metabolite by cytosolic enzymes. M2 is pharmacologically inactive. Excretion in the urine is about 65%, and the remainder is excreted in the feces.

Question 14

what does eNOS stand for

Answer 14

endothelial nitric oxide synthase

Question 15

what does iNOS require/

Answer 15

denovo synthesis - takes a few hours to be expressed

Question 16

what are the NOS

Answer 16

gasotransmitters

Question 17

nNOS: neurotransmission

Answer 17

long-term potentiation
coordination between neuronal activity and blood flow
pain modulation

Question 18

eNOS: cardiovascular EDRF

endothelial

Answer 18

• regulation of vascular tone
• inhibiton of SMC proliferation
• inhibition of platelet aggregation

Question 19

iNOS - inflammation and host defence

inducible

Answer 19

-cytoxicity against bacteria viruses and other microorganisms

Question 20

excess production of NO in endothelium/vascular smooth muscle leads to

Answer 20

hypotension (septic shock)

Question 21

inadequate production of NO in endothelium/vascular smooth muscle leads to

Answer 21

atherogenesis, thrombosis (e.g. hypercholesterolaemia, diabetes mellitus)

Question 22

what physiological role does NO play in platelets

Answer 22

limitation of adhesion and aggregation

Question 23

what physiological role does NO play in CNS

Answer 23

neuroransission, long term potentiation, plasticity (memory, appetite, penile errection)

Question 24

excess production of NO in CNS leads to

Answer 24

excitotoxicity - ischemic stroke, Huntingtons disease, AIDs dementia

Question 25

what physiological role does NO play in PNS

Answer 25

Neurotransmissionn - gastric emptying, penile errection

Question 26

inadequate production of NO in PNS leads to

Answer 26

hypertrophic pyloric stenosis, errectil disfunction

Question 27

how do nitric oxide donor work to help treat angina?

Answer 27

they cause blood vessels to dilate so chest pain is released

Question 28

examples of nitric oxide donors

Answer 28

amyl nitrite and GTN

Question 29

angina

Answer 29

inc HR, contract, after and preload - inc O2 consumption

Vasospasm, fixed stenosis, thrombosis - decreased coronary blood flow

Question 30

what does adding a spacer to an NSAID allow you to do? example

Answer 30

allows you to add another group to the drug

eg - aspain - spacer - NO releasing group

Question 31

How do NSAIDs cause topic irritation and direct epithelial damage?

Answer 31

COX1 is inhibited and so cannot synthesis PGE2 fro arachondonic acid - hence decreased mucus and bicarbonate secretions nd decreased blood flow - acid damage in the epithelium as no mucus to protect or bicarbonates to neutralise

Question 32

How do NSAIDs cause topic irritation and direct epithelial damage?

Answer 32

COX1 is inhibited and so cannot synthesis PGE2 fro arachondonic acid - hence decreased mucus and bicarbonate secretions nd decreased blood flow - acid damage in the epithelium as no mucus to protect or bicarbonates to neutralise

Question 33

what could NO releasing aspirin do?

Answer 33

help to reduce gastric bleeding?

Question 34

what is beetroot packed full of and how does this help vasodilation

Answer 34

beetroot is packed full of nitrate - breaks down and acidified - you get NO produced -

Question 35

how many ways are there to make H2S endogenously

Answer 35

4

Question 36

what pathologies would decrease with H2S perturbed bioavailability

Answer 36

diabetes, Coronary artery disease, pulmonary hypertension, ichemia and repercussion injury, renal failure and atherosclerosis

Question 37

what would increase with perturbed H2S

Answer 37

toxic shock, rheumatoid atheritis pancreatitis

Question 38

H2S pro proliferation factors

Answer 38

Kate channel, T-CA2+ channel, oxidative stress, AKT

Question 39

H2S pro apoptosis factors

Answer 39

NF-kB, cell cycle related kinases, cell death related genes, oxidative stress, MAPK

Question 40

what determines whether H2S kills or rescues cells

Answer 40

how it is administered

Question 41

does H2S have a target

Answer 41

mitochondria can use sulphide as an inorganic sulphur source - Used as substrate – take off electrons – bipass complex 1 and 2 - passed alont ETC – get ATP

Question 42

how do you target mitochondria

Answer 42

Matrix inside – highly negatively charged

Something – v lipophilic