2.0 Receptors Flashcards Preview

MedST IB: Mechanisms of Drug Action (MoDA) > 2.0 Receptors > Flashcards

Flashcards in 2.0 Receptors Deck (25)
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1

Adenosine

- Class = NANC transmitter
- Target = A1, A2A, A2B, A3 receptors
- Mechanism = Agonist
- Steps:
- Info:
Injected to treat supra ventricular dysrhythmias
A1 recetor inhibits renin release

2

Atropine

- Class =
- Target = muscarininc ACh receptor
- Mechanism = Non-selective antagonist
- Steps:
- Info:
Used to be used to induce pupil dilation (but too long lasting, thus now sympathetic agonists used instead)

3

B K 8644

- Class = Dihydropryridine
- Target = L-type voltage gated Ca²⁺ channel
- Mechanism = Agonist
- Steps:
Favours mode 2 of channel opening
- Info:
Same binding site as nifedipine
Only used experimentally

4

Benzylcholine mustard

- Class = Modified form of ACh
- Target = Muscarinic AChR
- Mechanism = Irreversible antagonism
- Steps:
1) Irreversibly alkylates muscarinic receptor
- Info:
Functions in a time dependent manner → progressive blockade of muscarinic receptors

5

Benzocaine

- Class = Local anaesthetic
- Target = Na⁺ channel
- Mechanism = Blocker
- Steps:
1) Non charged, therefore enters the cell using hydrophobic pathway
2) Not use-dependent
3) Not affected by pH
- Info:

6

alpha-Bungarotoxin

- Class = Toxin
- Target = nAChR at NMJ
- Mechanism = Irreversible antagonist
- Steps:
- Info:
Produced by branded krait snake

7

Cholera toxin

- Class = Toxin
- Target = Gαs subunit of G protein
- Mechanism = Causes increased activation of adenylyl cyclase
- Steps:
1) Causes ADP-ribosylation of αs
2) This inhibits GTPase activity → sustained activation of adenylyl cyclase
- Info:

8

Diltiazem

- Class = Benzothiazipine
- Target = L-type voltage gated Ca²⁺ channel
- Mechanism = Antagonist
- Steps:
Act on different sites than DHPs
Show use dependence
Preferentially targets cardiac tissue (because Ca²⁺ channels here have highest opening frequency)
- Info:
Ditliazem → ↑ DHP binding

9

d-Tubocurarine

- Class =
- Target = nAChR
- Mechanism = Antagonist
- Steps:
- Info:
Non selective between ganglionic and NMJ
Generated by purification of curare
Charged therefore not orally active

10

Ethinylestradiol

- Class = Steroid
- Target = Estrogen receptor
- Mechanism = Agonist
- Steps:
- Info:
Used in contraception
Estrogen receptor = exception to steroid receptors as it is found in nucleus unbound to ligand

11

Glibenclamide

- Class = Sulphonylurea
- Target = Sulphonylurea receptor (SUR)
- Mechanism = Agonist
- Steps:
Binds to SUR → closure of K⁺-ATP channel → depolarisation of panreatic β cells → opening of voltage gated Ca²⁺ channel → insulin release (exocytosis)
- Info:
Used in Type II DM

12

Isoprenaline

- Class = β agonist
- Target = β₁ + β₂
- Mechanism = Agonist
- Steps:
β₁ → ↑ heart rate
β₂ → bronchodilation
- Info:
Used to be used for asthma - now stopped because caused tachycardia

13

Lidocaine/lignocaine

- Class = Local anaesthetic (tertiary amine)
- Target = Na⁺ channel
- Mechanism = Blocker
- Steps:
1) Binds to and stabilises the inactive conformation of the channel
2) Crosses membrane in uncharged form
3) Blocks channel in charged form
4) Shows use dependence + voltage dependence
- Info:
Used as LA but also as antidysrhythmic (ventricular problems)
Selectivity for smaller and slower conducting fibres (Aδ + C)
Fast in-fast out kinetics (more effective at high rates of stimulation)

14

Minoxidil

- Class = K⁺ channel opener
- Target = ? K-ATP channel?
- Mechanism = Opener
- Steps:
Exact mechanism unknown
Opens K⁺ channel → K⁺ efflux → hyperpolarisation → relaxation of smooth muscle (e.g. that surrounding vasculature)
- Info:
Used in male baldness, hypertension, asthma, IBS
- side effect:
May cause hyperglycaemia by limiting insulin secretion by pancreatic β cells

15

Nicorandil

- Class = K⁺ channel opener
- Target = ? K-ATP channel?
- Mechanism = Opener
- Steps:
Exact mechanism unknown
Opens K⁺ channel → K⁺ efflux → hyperpolarisation → relaxation of smooth muscle (e.g. that surrounding vasculature)
- Info:
Used in HTN and angina (causes ischaemic preconditioning)
Also an NO donor
- side effect:
May cause hyperglycaemia by limiting insulin secretion by pancreatic β cells

16

Nifedipine

- Class = Dihydropryridine
- Target = L-type voltage gated Ca²⁺ channel
- Mechanism = Antagonist
- Steps:
Favours mode 0 of channel opening (inactive state)
Preferentially stabilises inactive channel, thus favours tissues which are constitutively depolarised (e.g. vascular smooth muscle)
Use dependence
- Info:
Same binding site as Bay K 8644
Used for HTN and angina
Reduces aldosterone secretion

17

Norethisterone

- Class = Steroid
- Target = Progesterone (progestagen) receptor
- Mechanism = Agonist
- Steps:
- Info:
Used in contraception

18

Pertussis toxin

- Class = Toxin
- Target = Gαi subunit of G protein
- Mechanism = Causes increased activation of adenylyl cyclase
- Steps:
1) Causes ADP-ribosylation of αi
2) This prevents GDP→GTP exchange
3) Prevents activation of Gαi → ↑ PKA activity
- Info:
↑ PKA activity → loss of water through intestine → severe dehydration

19

Prednisolone

- Class = Steroid
- Target = glucocorticoid receptor
- Mechanism = Agonist
- Steps:
- Info:
Used for inflammatory/autoimmune conditions
Has a lymphocytic effect (useful against leukaemias)
Administered as prodrug prednisone (converted to prednisolone in liver)

20

Quinidine

- Class = Local anaesthetic
- Target = Na⁺ channel
- Mechanism = Blocker
- Steps:
1) Shows use dependence
2) Slow in-slow out kinetics therefore shows use dependence at lower rates of stimulation
- Info:
Also used as antidysrythmic (Class 1A)

21

Spironolactone

- Class = K⁺ sparing diuretic
- Target = Aldosterone (mineralocorticoid) receptor
- Mechanism = Antagonist
- Steps:
Spironolactone is metabolised to canrenone in the liver
Canrenone and its K+ salt (potassium canrenone) work as K+ sparing diuretics
Spironolactone/canrenone compete with aldosterone binding site on cytoplasmic receptor
Antagonism → ↓ expression of Na⁺/K⁺ ATPase and ENaC → ↓ Na⁺ reabsorption
- Info:
Acts on distal tubule
Rate of onset of diuresis is slow

22

Tamoxifen

- Class = Estrogen antagonist
- Target = Estrogen receptor
- Mechanism = Competitive antagonist
- Steps:
Has lower affinity than oestrogen. Reduces the transcription of estrogen response genes.
- Info:
Used for breast cancer
Can have agonist effects in bone and uterus

23

Tetradotoxin

- Class = Toxin (guanidium)
- Target = Na⁺ channel
- Mechanism = Blocker
- Steps:
Contains guanidium group
Blocks Na⁺ channel from outside
No use-dependence
- Info:
Puffer fish
Does not affect cardiac channels because of the presence of cysteine residues in the cardiac Na⁺ isoform

24

Tyrphostins

- Class = RTK inhibitors
- Target = Receptor tyrosine kinase
- Mechanism = Inhibition
- Steps:
- Info:
Potential use in the treatment of neoplasms by blocking RTKs implicated in cellular proliferation.
Example = Glivec for treating CML

25

Verapamil

- Class = Phenylalkylamine
- Target = L-type voltage gated Ca²⁺ channel
- Mechanism = Antagonist
- Steps:
Act on different sites than DHPs
Show use dependence
Preferentially targets cardiac tissue (because Ca²⁺ channels here have highest opening frequency)
- Info:
Verapamil→ ↓ DHP binding