Lecture Course 1: Drug Interactions

Question 1

* Benzilylcholine Mustard *

Answer 1

Non selective antagonist for muscarinic receptors.

Irreversibly alkylates the receptor.

Unstable cyclised ring breaks and covalently binds to alkylated receptor.

Question 2

* Cholera Toxin *

Answer 2

ADP-ribosylates alpha-s subunit of G proteins.

This inhibits GTPase activity resulting in sustained activation of adenylyl cyclase and raised cAMP.

Question 3

* Pertussis Toxin *

Answer 3

ADP-ribosylation of alpha-i subunit of G proteins.

Prevents activation of alpha-i in response to receptor stimulation.

Raises cAMP.

Question 4

Lithium

Answer 4

Inhibits conversion fo IP1 to inositol by acting on the phosphatase. => blocks inositol recycling. Used in treatment of bipolar disorder, as brain relies solely on inositol recycling due to blood brain barrier.

Question 5

epidermal growth factor (EGF) and platelet derived growth factor (PDGF)

Answer 5

Acts on a receptor tyrosine kinase. Autophosphorylation results in recruitment of SH2 domains, leading to downstream effects

Question 6

* Prednisolone *

Answer 6

Glucocorticoid agonist (steroidal)

Positive Dennis binds the glue

Question 7

Mifepristone

Answer 7

Glucocorticoid antagonist (steroidal)

Priest Miffy frowns on solvent use (glue)

Question 8

Fludrocortisone

Answer 8

Mineralocorticoid agonist (steroidal)

Minerals in fluid are good for you

Question 9

* Spironolactone

Answer 9

Mineralocorticoid antagonist (steroidal)

Diuretic

Spiral out the minerals in the pee

pee

Question 10

* Ethinylestradiol

Answer 10

Estrogen agonist (steroidal)

Contraceptive

Ethan is on the pill

Question 11

* Tamoxifen *

Answer 11

Estrogen antagonist (steroidal)

Breast cancer treatment

Tamagotchis against estrogen

Question 12

* Norethisterone *

Answer 12

Progesterone agonist (steroidal)

Contraception

Pro contraception, nor birth control

Question 13

Danazol

Answer 13

Progesterone antagonist (steroidal)

Danny hates pros

Question 14

* Lidocaine (and Procaine)

Answer 14

Local anaesthetic:

• Stabilises sodium channels in inactivated state => hyperpolarisation
• Charge dependent
  
  • Blocks best when in charged state (at high pH)
• Use dependent - ‘fast in, fast out’
  
  • Blocks inactivated channels
  • Initial block increased by giving a hyperpolarising pre-pulse

Class IB antidysrythmic

Question 15

QX314

Answer 15

Local Anaesthetic

• Blocks sodium channels
• Charged - cannot cross membranes

Question 16

* Benzocaine *

Answer 16

Local Anaesthetic

• Uncharged sodium channel blocke
• No pH dependence but works via both hydrophilic and hydrophobic pathways.
• Hydrophilic pathway (use dependent) - blocks channel via cytoplasm
• Hydrophobic - blocks channel via membrane

Question 17

*Quinidine*

Answer 17

Local Anaesthetic

• Na channel blocker
• Use dependence at low rates of stimulation - ‘slow in, slow out’

Class IA antidysrhythmic

Question 18

* Tetrodotoxin *

Answer 18

• Block sodium channels externally.
• No use dependence

.

Question 19

* Bay K 8644 *

Answer 19

• Dihydropyridine.
  
  • ‘Calcium agonist’
  • Gain access to channel via membrane
  • L type calcium channel - Favour Mode 2 (long opening) => macroscopic currents
• Binding:
  
  • reduced by verapamil
  • enhanced by diltazem

Question 20

* Nifedipine

Answer 20

• Dihydropyridine
  
  • calcium VG channel antagonist.
  • L-type : favour mode 0 - no Calcium flow
  • Antihypertensive

Question 21

* Verapamil and Diltiazem

Answer 21

VG Calcium channel blocker - preferentially block cardiac calcium channels.

• Phenylalkylamine and benzothiazepine respectively.
• Binding site: separate but interacting with DHP binding site:
  
  • Verapamil inhibits DHP binding
  • Diltazem enhances DHP binding
• Class IB antidysrythmic. Affects nodal tissue, high in L type and T type
• Use dependence - reach binding site when channel is open

Question 22

*Glibenclamide* (& Tolbutamide)

Answer 22

• Close Katp channels by acting on the sulphonylurea receptor.
• Less potassium efflux => depolarisation opens VGCa2+ channels, stimulating insulin release. Orally acting hypoglycaemic agents
• Type II diabetes