TO RECALL 2 Flashcards
General NSAID MOA
Inhibiting the prostaglandin (PG) G/H synthase enzyme or cyclooxygenase (COXs)
act as antipyretic, analgesic, and anti-inflammatory
Drug:
Aspirin
- only irreversible inhibitor of the COX enzymes (COX-1 and COX-2)
- has cardioprotective effects
- cannot be given to children and young adults below 20 y.o. due to Reye syndrome
Drug:
Acetaminophen (paracetamol)
- effective antipyretic and analgesic
- partly inhibits COXs - reversible
- NSAID with weak anti-inflammatory activity
Side effects of inhibition of COX-1
(1) Gastric adverse events - COX-1 is the dominant cytoprotective isoform in gastric epithelial cells
(2) Bleeding - COX-1 forms TxA2 in platelets which amplifies platelet activation and constricts blood vessels at site of injury
Side effects of COX-2 inhibition
(1) exacerbate hypertension - COX-2 plays important roles in blood pressure regulation
(2) increases likelihood of thrombotic events - COX-2 act as endogenous inhibitors of hemostasis
Aside from the usual Neurotransmitters, enumerate additional peptides, purines, and small molecules that can be used.
(Peptides): enkephalin, substance P, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin
(Purines): ATP and Adenosine
(Small molecules): Nitric Oxide
In a neuron, the resting potential is (1), the threshold potential is (2), the intracellular ion is (3), and the extracellular ion is (4),
(1) -70 mV
(2) - 55 mV
(3) K+ , potassium has a high concentration inside the cell
(4) Na+, sodium has a low concentration inside the cell but have a high concentration outside
Posion
Tetrodotoxin
- secretions from puffer fish
- block the voltage gated Na+ channel which prevents depolarization
Poison
Saxitoxin
- secretions from shellfish
- block the voltage gated Na+ channel which prevents depolarization
Poison
Batrachotoxin
- toxin from the South American Frog
- extremely potent steroidal alkaloid
- it increases the permeability of Na+ channel causing hyper-depolarization paralysis
Poisons
Scorpion Toxin
Causes persistent depolarization by inhibiting its deactivation
Drug
Hemicholinium
- blocks CHT1 (choline transporter 1 or SLC5A7) a Na+ and Cl- dependent transporter in presynaptic membranes of cholinergic neurons
Drug
Vesamicol
- functions as a noncompetitive and reversible inhibitor of acetylcholine uptake in storage vesicles
Drug
Botulinum toxin
- blocks ACh release by interfering with the machinery of transmitter release (exocytosis of storage vesicle to release neurotransmitters)
- cleaves SNARE proteins
- at Neuromuscular Junction (NMJ)
Poison
Tetanus toxin
- similar to botulinum toxin but acts in the CNS
- cleave SNARE protein synaptobrevin to block exocytosis and release of acetylcholine
Drug
ACE inhibitors
- block acetylcholinesterase to increase interaction of post synaptic neuron with acetylcholine
Drug
Trimethaphan and Mecamylamine
Neuronal nicotinic antagonists
Muscarinic Receptors (M1, M2, M3, M4, M5)
- G protein coupled
- M1, M3, M5 - increase cAMP
- M4, M5 - decrease cAMP
Predominant parasympathetic receptor subtype in the heart
Muscarinic receptor (M2)
Muscarinic receptors (M1, M3, and M5) take effect by what signaling pathway?
(1) Gq/11
(2) stimulates the PLC-IP3/DAG-Ca2+ pathway
(3) activation of PKC and Ca2+ sensitive enzymes or PLA2 leading to the release of arachidonic acid and consequent eicosanoid synthesis
Muscarinic receptors (M2 and M4) take effect by what signaling pathway
(1) Gi and G0
(2) resulting to inhibition of adenylyl cyclase
(3) decrease in cellular cAMP, activation of inwardly rectifying K+ channels, and inhibition of voltage-gated Ca+ channels
(4) hyperpolarization and inhibition of excitable membranes
Tyrosine acted on by tyrosine hydroxylase (3-hydroxylated) and decarboxylated produces
Dopamine
Dopamine is converted to Norepinephrine via
Dopamine Beta-hydroxylase
Norepinephrine acted on by N-methyltransferase produces
Epinephrine
