DRUGS Flashcards
TTX
Na+ channel inactivation
TEA
K+ channel inactivation, but non selective so it can target Ca2+ channels and also target the nAChRs
Cocaine
Agonist of NA+ channels in use dependent competitive manner - 3% actually binds to Na+ channels O’Leary 2010 - joyous feelings arise from the indirect agonist of dopamine reuptake receptors (DAT)
Derivatives of cocaine used because
Coke takes ages to unbind from Na+ receptors - and hence the effects cannot be appropriately mediated - 8x slower - Crumb and Clarkson 1990
3 major discoveries of the synapse
1936 Loewi and Dale NP - demonstrated that transmission was chemical
Loewi - placed two frog hearts in a bath and slowed the first - the second slowed two and determined the substance was Vagustoff
Dale then determined this was ACh with experiments on leech muscle
Vesicles - then from the coloured with histochemical staining then electron microscopy - Koelle et Al - 1949
Fatt and Katz - 1954 - determined the vesicular and quantal nature of ACh release - mEPPs - determined too big to be of just one ACh molecule and that they were uniform in size
Turbocuraine
NMJ - Non depolarising competitive antagonist of nAChRs - long duration paralytic
Suxamethonium
Depolarising direct cholinergic agonist - intermediate fasiculation
Sarin nerve gas
Inhibits by competitive binding AChE - seizures and resp arrest
Organophosphates
AChE inhibitors also excess muscarinic and nicotinic action
Botulinum toxin
Cleaves SNAP 25 - no partial fusion so no vesicular release
Myaesthenia Gravis
IgG autoantibodies - bind to and increase the rate at which the receptor itself is degraded - treated with AChEs
Atropine
Anticholinergic muscarinic competitive antagonist - acts on M2 (inhibits an inhibitory) - at vagus nerve junction
Pirenzepine
Muscarinic M2 receptor antagonist - inhibits gastric acid secretion
Gallamine
M2 competitive antagonist - muscle relaxation in general anaesthetic
Darifenacin
M3 agonist located in smooth muscle (bladder)
Hess experiment
1920s - invented interrupted DC and paced it through a cats brain - could induce higher HR and a generalised stress state - termed the region the arcuate nucleus of the hypothalamus
Alpha 1 both
Gq
Agonist - phenylephrine - activation of α1-adrenoceptors in the arterioles of the nasal mucosa. This causes vasoconstriction, which leads to decreased edema and increased drainage of the sinus cavities.
Antagonist - prazosin - relaxed muscle, including blood vessels and therefore lowers blood pressure
Alpha 2 both
Gi
Agonists - methyldopa antihypertensive - all normally oppose the effects of the sympathetic nervous system to produce sedation, analgesia, and euphoric effects and partially block acute withdrawal symptoms in chronic opioid users
Antagonist - mirtazapine - dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonising the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors and increase sympathetic action
Beta 1 both
Gs
Agonist - dobutamine - inotropic effect increases contractility, leading to decreased end-systolic volume and, therefore, increased stroke volume
Antagonist - metoprolol - cardiac output by negative inotropic and chronotropic effects and decreases sympathetic activity
Beta 2 both
Gs
Agonist - albuterol - relaxes the bronchial smooth muscle. It also inhibits the release of immediate hypersensitivity mediators from cells, especially mast cells to treat/ prevent bronchospasm
No selective beta 2 antagonists
M3
Agonist - Pilocarpine - By directly stimulating these receptors, pilocarpine causes smooth muscles, such as the iris sphincter muscle and ciliary muscle, to contract
Antagonist - tiotropium - bronchodilation by relaxing and opening the air passages to the lungs to make breathing easier
M1
Agonist - sabcomeline - though in spite of important cognitive enhancing effects, most trials have been discontinued due to considerable side-effects
Antagonist - scopolamine - central nervous system (CNS) to create a calming effect on the muscles in the stomach and bowels (gut) post anaesthesia anti-nausea
