drugs Flashcards
Riluzole
Positive allosteric modulator of the Na+/K+ dependent Glutamate transporter on the plasma membrane of glial cells and neurons. Increases the Glu re-uptake, thus exerting a neuroprotective action.
Amphetamines
False substrate of the Na+/Cl- dependent transporter of biogenic amines on the nerve terminal and on the synaptic vesicles. Amphetamines are transported inside the nerve terminal and the vesicles in exchange for NA or DP therefore causing a durable build-up of the NT-level in the synaptic cleft.
Cocaine
Inhibitor of the transporter for biogenic amines and causes NT build-up in the cleft by inhibiting the re-uptake and enhances the sympathetic transmission. It has side effects on the cardiovascular level. (short acting)
Methylphenidate
Aka Ritalin; inhibits the re-uptake of DA and NA and is used to treat ADHD in children.
Fluoxetine
Selective Serotonin Re-uptake inhibitor; bind to a different binding site to the substrate and enhance serotoninergic transmission. Have side effects in the intestine as serotonin plays a major role there.
Imipramine
Tricylic antidepressant; inhibit NET competitively and have much less effect on dopamine uptake. Wide array of off-target effects: interact with muscarinic acetylcholine receptors and ion channels.
Digoxin
Cardiac glycoside; competitive inhibitors of the Na+/K+ pump in cardiac myocytes by binding to the K+ bindig site. Na+ levels inside the cells are raise, which causes the Na+/Ca2+ exchanger to change its flow and pump Ca2+ inside the cell. As a consequence a stronger heart contraction is promoted. Increased toxicity at low K+ conc and narrow therapeutic margin (causes dysrhythimas)
Omeprazole
Proton pump inhibitor; irreversible inhibitors of the H+/K+ pump on the apical membrane of gastric paretial cells. Omeprazole (racemic mixture) is a pro-drug and a weak base that accumulates in the acid environment of the canaliculi of the stimulated paretial cells where it is protonated into sulphenamide and covalently binds to SH groups of the PP.
Furosemide
loop diuretic; inhibit the Na+/K+/Cl- symporter in the ascending limb of Henle’s loop by binding to the Cl- binding site. Major side effect is the K+ loss in the collecting ducts: K+ are transported into collecting ducts by Na+/K+ ATPase on the basolateral membrane and leak into the lumen through K+ selective ion channels. Na+ passes through sodium channels in the apical membrane down the gradient generated by the ATPase. When more Na+ reaches the ducts more K+ is secreted to maintain that gradient. Have a blood pressure lowering effect by decreasing the ventricular filling.
Thiazides
Thiazide diuretics; competitive inhibitors of the Na+/Cl- symporter in distal tubule in kidney; are more potent than loop diuretics and are therefore used at lower doses. Cause a major loss of K+ in the collecting ducts, but don’t cause Ca2+ loss
K+ sparing diuretics
Aldosterone R inhibitors; compete with aldosterone for its intracellular receptor and decrease the expression of Na+/K+ ATPase and epithelial Na+ channels in the collecting ducts. Prevent hypokalemia and are therefore used in combination with other diuretics
Probenecid
non-selective inhibitor of the uric acid transporter on the apical membrane of renal proximal tubule cells and increase the uric acid secretion by preventing its reabsorption. Also inhibits SLC transporters on the basolateral membrane of renal proximal tubule cells
Lesinurad
selective uric acid transporter inhibitor for the treatment of gout
Elobixibat
inhibitor of the ilieal bile acid transporter responsible for the re-uptake of bile acids; increases the bile salt concentration in the gut and lowers cholesterol levels
Metformin
insulin sensitizer; indirectly target insulin dependent glucose transporters in insulin target tissues. GLUT-4 translocates to the membrane in response to IR activation or when energy demand is high. Metformin activates AMPK, which signals a low energy state (AMP/ATP ratio is high) and decreases hepatic glucose production and promotes glucose uptake.
Glifozins
competitive selective SGLT2 inhibitors on the apical membrane of proximal tubules responsible for the secondary active reabsorption of glucose against its concentration gradient. They cause the kidney to remove glucose from the body through the urine. Side effect: hypertension due to an osmotic effect.
Ivacaftor
Potentiator that increases the functional activity of CFTR channels. Used in cystic fibrosis when a mutation that causes an impaired protein activity is present (G551D). Work by. increasing the open-probability of the channel
Lumacaftor
Corrector that improves the intracellular processing of channel proteins and increase the amount of cell-surface localized proteins. Used for cystic fibrosis when a mutation the causes a reduced amount of protein is present. (Phe508del)
Ataluren
production corrector that prevents premature termination of translation of CFTR channel proteins
Gabapentin
mimics GABA and is approved for epilepsy treatment. Characterized by a non-linear PK profile, since the transporter saturates at clinically used dose. Drug can be chemically modified to pro-drug that hydrolyzes to gabapentin and that is recognized by high capacity MCT-1 transporters in order to improve the PK profile
Lidocaine
local anesthetic that blocks sodium channels in peripheral nerves and prolong the refractory period by binding with high affinity to open. Bind to channel with protonated aminic group and reach the channel through the hydrophilic pathway (use-dependent). Low degree of selectivity : direct vasodilator action and absorption into systemic circulation (administered with adrenalin to avoid this)
Nifedipine
Dihydropyridine; calcium channel blocker that targets Ca2+ channels in the vessels and thus has a antihypertensive effect.
Verapamil
Phenylalkylamine; calcium channel blocker that targets Ca2+ channels in the heart and thus has an antiarrhythmic effect
Diltiazem
Benzothiazepine; Calcium channel blocker that has an intermediate actio on both heart and vessel
GIRK
K channels activated by the beta-gamma subunit of G-proteins in heart and the CNS. Opening causes hyperpolarization and slower heart rate. Indirect target GPCR antagonists or agonists
Sulphonylureas
target ABC family accessory protein of ATP regulated K channels SUR in pancreatic cells. Mimic the ATP increase and therefore cause the channel to close which leads to a depolarization of the cell membrane and the opening of Ca2+ channels that facilitate insulin secretion. Undesired side effects by targeting isoform with different SUR unit in heart and carry risk of hypoglycemia
Minoxidil
K+ channel opener; pro-drug that acts as a potent vasodilator by increasing the activity of K+ channels that leads to a hyperpolarization of the membrane. As a consequence Ca2+ channels are closed
Capsaicin
targets TRPV channels in sensory neurons that are poorly sensitive to changes in membrane potential and works by channel desensitization
tubocurarine
non depolarizing drug; competitively blocks muscle nicotinic avetylcholine receptors on the neuronal muscle junction by antagonizing Ach. Effect is reversible by the action of Ach-esterase or by sugammadex
Suxamethonium
depolarizing durg; selectively binds and activates nicotinic acetylcholine receptors. The prolonged activation with Ach-esterase resistant drugs results in channel desensitization. The block cannot be reversed.