Lecture Course 1: Drug Interactions Flashcards
* Benzilylcholine Mustard *
Non selective antagonist for muscarinic receptors.
Irreversibly alkylates the receptor.
Unstable cyclised ring breaks and covalently binds to alkylated receptor.
* Cholera Toxin *
ADP-ribosylates alpha-s subunit of G proteins.
This inhibits GTPase activity resulting in sustained activation of adenylyl cyclase and raised cAMP.
* Pertussis Toxin *
ADP-ribosylation of alpha-i subunit of G proteins.
Prevents activation of alpha-i in response to receptor stimulation.
Raises cAMP.
Lithium
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.
epidermal growth factor (EGF) and platelet derived growth factor (PDGF)
Acts on a receptor tyrosine kinase. Autophosphorylation results in recruitment of SH2 domains, leading to downstream effects
* Prednisolone *
Glucocorticoid agonist (steroidal)
Positive Dennis binds the glue
Mifepristone
Glucocorticoid antagonist (steroidal)
Priest Miffy frowns on solvent use (glue)
Fludrocortisone
Mineralocorticoid agonist (steroidal)
Minerals in fluid are good for you
* Spironolactone
Mineralocorticoid antagonist (steroidal)
Diuretic
Spiral out the minerals in the pee
pee
* Ethinylestradiol
Estrogen agonist (steroidal)
Contraceptive
Ethan is on the pill
* Tamoxifen *
Estrogen antagonist (steroidal)
Breast cancer treatment
Tamagotchis against estrogen
* Norethisterone *
Progesterone agonist (steroidal)
Contraception
Pro contraception, nor birth control
Danazol
Progesterone antagonist (steroidal)
Danny hates pros
* Lidocaine (and Procaine)
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
QX314
Local Anaesthetic
- Blocks sodium channels
- Charged - cannot cross membranes
* Benzocaine *
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
*Quinidine*
Local Anaesthetic
- Na channel blocker
- Use dependence at low rates of stimulation - ‘slow in, slow out’
Class IA antidysrhythmic
* Tetrodotoxin *
- Block sodium channels externally.
- No use dependence
.
* Bay K 8644 *
- 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
* Nifedipine
- Dihydropyridine
- calcium VG channel antagonist.
- L-type : favour mode 0 - no Calcium flow
- Antihypertensive
* Verapamil and Diltiazem
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
*Glibenclamide* (& Tolbutamide)
- 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
