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169 Cards in this Set
- Front
- Back
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What do PPAR α/γ ligands do?
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Increase insulin sensitivity
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Therepeutic targets of T2DM? Three
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Increase insulin secretion
Increase insulin sensitivity Lower blood glucose independent of insulin |
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What do Sulphonylureas do?
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Increase insulin secretion
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What do Phenyalinine anologues do?
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Increase insulin secretion
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What do GLP-1 Mimetics do?
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Increase insulin secretion
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What do DPP IV inhibitors do?
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Increase insulin secretion
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What do Biguanides do?
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Lower blood glucose
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What do a-glucosidase inibitors do?
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Lower blood glucose
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What do SGLT2 inhibitors do?
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Lower blood glucose
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Tolbutamide
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Sulphonylurea
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Glibenclamide
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Sulphonylurea
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Chlorpropamide
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Sulphonylurea
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Glipizide
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Sulphonylurea
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Gliclazide
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Sulphonylurea. More selective for b-ceell Katp SUR1 subunit.
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11p15.1
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chromosome related to sulfonylurea receptor.
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Isoforms of SUR receptor?
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SUR1, 2A, 2B
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Where do Sulphonylureas bind?
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SUR subunit
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Side effects of sulfonylureas?
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Post-prandial hypoglycemia, Cardiovascualr(Katp channels in heart)
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Which sulfonylurea is more selective for beta cell Katp SUR1 subunit?
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Gliclazide
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Nateglinide
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Phenylalanine Analogue
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Repaglinide
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Phenylalanine Analogue
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Target of Phenylalanine Analogues?
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B-cell Katp channels.
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Side effects of Phenylalanine Analogues?
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None
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GLP-1
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Enteric Incretin hormone. degraded via DPP IV
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DPP IV. Degrades what(significant to diabetes)
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Peptidase. Degrades GLP-1.
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How are GLP-1 mimetics delivered?
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Subcutaneus
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Exenatide
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GLP-1 mimetic, 53% homology from glia monster
NOT A DPP IV substate |
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Liraglutide
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FA deriviative of GLP-1
Not a DPP IV substrate True GLP-1 anologue |
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Ends in Glutide what is it?
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GLP-1 mimetic
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Ends in inide what is it?
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Phenylalinine anologue
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Ends in izide what is it?
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Sulphonylurea
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Ends in amide what is it?
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Could be a sulphonylurea
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Sitagliptin
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DPP IV inhibitor
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Vildagliptin
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DPP IV inhibitor
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Ends in gliptin what is it?
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DPP IV Inhibitor
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Side effects of DPP IV inhibitors?
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Immune related
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Finofibrate
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PPAR A sensitive ligand
Insulin sensitizer |
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Piogliazone
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PPAR γ-selective ligand
Insulin sensitizer |
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Rosiglitazone
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PPAR γ-selective ligand
Insulin sensitizer |
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Side effects of Insulin sensitizers? Making it contraindicated for?
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Weight gain, fluid retention
CHF and Hepatic dysfunction |
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SGLT
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facilitate co-transport of sodium and glucose
Sodium Glucose Transporter |
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SGLT isoforms? Locations of isoforms?
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SGLT-1 in GI
SGLT-2 kidneys |
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Dapagliflozin
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SGLT-2 specific inhibitor
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Side effects of SGLT-2 inhibitors?
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Urinary tract infections and genital infections.
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Biguanides
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Increase glucose uptake
Decrease appetite lower VLDL and LDL Increase B-cell responsiveness |
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Meltformin
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A Biguanide, increased glucose uptake to skeletal muscle
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α-Glucosidase Inhibitors
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α-glucosidase releases glucose from more
complex carbohyrdates starch, dextrin, maltose and sucrose |
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Acarbose
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α-Glucosidase Inhibitor
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Side effects of α-Glucosidase Inhibitors
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GI- Flatulence, Diarrhea
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Future directions for T2DM
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Glucokinase activators
Sirtuins Glucagon receptor antagonists |
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What do statins do?
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Inhibit cholesterol biosynthesis vi HMG-CoA reductase
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What do Fibrates do?
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Decrease FA and TG levels
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What do Resins do?
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Bind/sequester bile acids.
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What is atorvastatin
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HMG-CoA reductase inhibitor
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What is simvastatin
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HMG-CoA reductase inhibitor
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What is gemfibrozil
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Fibrate, lowers FA and TG
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What is fenofibrate
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Fibrate, lowers FA and TG
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What is cholestyramine
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A Resin, binds bile acids, lowers cholesterol
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Statins mechanism of action, (selectivity affinity type of binding)
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Selective, reversible,competitive inhibitors
Affinity 1000-10000 times natural substrate |
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Statins effects and pleiotropic effects
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Lower LDL,Lower TG, More LDL receptors.
Pleiotropic effects- endothelial, platelet aggregation, anti-inflammatory |
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Statins Adverse effects and monitoring?
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Mostly minor but Rhabdomyolysis- muscle breakdown, debris causes renal failure.
Not in pregnant(germ migration) Monitor creatine kinase and liver enzymes. |
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Statins interactions
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CYP3A4 enzyme. Therefore grapefruit juice.
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How do fibrates work?
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Activate transcription factor PPAR-a
increase lipoprotein lipase decrease VLDL production lower inflammation INCREASE HDL Increase bile excretion |
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Who to use fibric acid derivitives with? Statins? Bile acids?
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Raised TG and cholesterol or low HDL.
CHD preventative or treatment. When Statins contraindicated |
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Nicotinic acid
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Adjunct to diet and statins. Lower TGs and LDL increase HDL.
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Ezitimibe
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block cholesterol absorption by blocking NPC1L1 xport protein. Used as adjunct, lowers LDL
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NPY
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neuropeptide Y. Group 1. Activated by falling leptin. Orexigenic/Anabolic.
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AGRP
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agouti-related-peptide. Group 1. Activated by falling leptin. Orexigenic/Anabolic.
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POMC
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Prepro-opiomelanocortin. Group 2. Activated by rising leptin. Anorexigenic. Catabolic.
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α-MSH
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α-melanocyte-stimulating hormone. Group 2. Activated by rising leptin. Anorexigenic. Catabolic.
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How many CCK receptors? What do they do?
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two CCK A in GI and CCK B in brain. CCK A- inhibit food intake.
CCK B- satiety factor. |
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CCK what is it what does it do?
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Cholecystokinin, peptide from mucosal in duodenam released from digestion of foods. (esp fat)
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PYY and OXM
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Peptide tyrosine tyrosine and Oxyntomodulin. Short-term satiety signals from mucosa
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Ghrelin
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Peptide from gastic mucosa. High in fast low during or before meal. Decreases leptin and vice versa.
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Sibutramine-side effects
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inhibits 5-HT,DA,NA reuptake and hypothalamic sites regulating food intake. Increases satiety.
Incr. BP. |
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Orlistat
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Irreversible inhibitor of gastric and pancreatic lipase. Not systematically absorbed. Dose-dependent.
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Rimonabant
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CB1 antagonist. lateral hypothalamus projects to limbic. Decreases reward. Peripheral effects.
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Acarbose
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α-glucosidase inhibitor. Delays carb absorption and post-prandial bood sugar spike. Diabetes treatment as well... Pre diabetes.
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Isoniazid
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Anti-bacterial used for tuberculosis, found to be a MAOI
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Reserpine
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Anti-hypertensive. Depletes monoamines in nerve terminals. Precipitated clinical depression.
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BDNF is what
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Brain Derived Neuronal Factor, stimulates TrkB receptors. anti-depressant.
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anti-depressant receptor of 5-HT. type of receptor?
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5-HT1A. an autoreceptor.
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anti-depressant receptor of NA type of receptor?
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α2 receptors which are autoreceptors.
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Categories of anti-depressants
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MAOIs
Uptake inhibitors Atypicals |
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MAO subtypes and locations
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MAO-A in neuronal mt-NA/5-HT
MAO-B in neuronal mt- DA MAO-A in gut wall - TYR |
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How does MAO deactivate?
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Deaminates by turning into aldehyde.
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Iproniazid
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Irriversible unselective MAO inhibitor. Hydrozine derivative.
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Isoniazid
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Irriversible unselective MAO inhibitor. Hydrozine derivative.
TB drug. |
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Isocarboxazid
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Irriversible unselective MAO inhibitor. Hydrozine derivative
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Phenelzine(PLZ)
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Irriversible unselective MAO inhibitor. Hydrozine derivative. Still popular
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Tranylcypromine(TCP)
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Irriversible unselective MAO inhibitor. Hydrozine derivative. Still popular
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RIMA
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Reversible inhibitor of monoamine oxidase-A
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Moclobemide
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A Reversible inhibitor of monoamine oxidase-A. Only used clinically.
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Toloxatone
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Reversible inhibitor of monoamine oxidase-A.
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Sumatryptin
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Serotonin agonist, do not take with MAOi
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Phenylephrine
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MAO substrate do not take with MAOI
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Commonest MAO-A inhibitor side effect
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orthostatic hypertension due to down regulation of vascular adrenergic receptors.
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NET
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Noradrenaline xporter. 1NA+/1CL-
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SERT
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5-HT 1NA+:1Cl-(in) and 1K+ out
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1st Uptake pump inhibitor?
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Imipramine
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Imipramine
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originally anti-szchizophrenic, didnt work but worked for depression. tricyclic antidepressant. MOST LIKE 5-HT
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Chlorpromazine
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uptake pump inhibitor. tricyclic antidepressant
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Desipramine
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metabolite of Imipramine demethylated. tricyclic antidepressant
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Clomipramine
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chlorinated otherwise identical to Imipramine. tricyclic antidepressant
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Protriptyline
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tricyclic antidepressant
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Amitriptyline
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tricyclic antidepressant.
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Nortriptyline
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tricyclic antidepressant
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Tricyclic sides.
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Anti-muscarinic.
H1 in brain(drowsiness) Postural hypotension |
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Imipramine similar to
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5-HT Ach and Histamine
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trend in t1/2
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less like Imiprimine more t1/2
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Tricyclics ADME
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Poor bioavailability.
Long half lives. High volume distribution. |
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Fluoxetine
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First SSRI
No anti-muscarinic no anthistamine |
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Fluvoxamine
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SSRI
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Sertraline
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SSRI-More DA
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Paroxetine
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SSRI-more DA
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Citalopram
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SSRI
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Side effects SSRI
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Nausea,Sexual problems,Serotonin discontinuation syndrome.
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Venlafaxine
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SNRI. Lack of affinity for DATs, muscarinic or histamine.
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Trazadone
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Atypical anti-depressant
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Bupropion
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Atypical anti-depressant
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Mianserin
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Atypical anti-depressant
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Maprotiline
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Atypical anti-depressant
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Synonyms for anti-psychotics
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Neuroleptics, Major tranquilizers
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COMT
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Gene in schizophrenia
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α7nAChR
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gene in schizophrenia
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What brain systems associated with Schizophrenia?
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DA neuronal pathways in mesolimbic/mesocortical system of brain.
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Apomorphine
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D2 agonist, mimic schizophrenia
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Bromocriptine
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D2 agonist, mimic schizophrenia
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Potency of anti-psychotics related to
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Affinity for D2 receptor
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3 theories of schizophrenia
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DA,5-HT,GABAergic
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Characterize GABA (glutamate) theory of schizophrenia
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Information from Striatum to Thalamus screened by glutamate.
Too little glutamate or too much DA inhibits GABAergic input to the thalamus. |
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Chlorpromazine
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1st anti-psychotic. used on battlefield 1st. synthesized in search for antihistamine and sedative action
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Classes of antipsychotics
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Phenothiazenes
Thioxanthenes Butyrophenones Misc(atypical) |
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Phenothiazenes
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Drugs based on chlorpromazine. Classical anti-psychotics
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Thioxanthenes
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Classical anti-psychotic. Phenothiazine nucleus with a cis double bond to the sidechain
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Butyrophenones
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Classical anti-psychotic.
Discovered while looking for morphine-like analgesics |
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Atypical anti-psychotics. Advantages?
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Fewr extrapyrmidal sides. Better at (-) symptoms. Better in treatment resistant.
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What structural requirement needs to be met for good anti-psychotic activity
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3 carbons between charged nitrogen and ring system
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Ends in AZINE ..?
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Most likely a Phenothiazine anti-psychotic.
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Chlorprothixene
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Thioxanthene anti-psychotic
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Thiothixene
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Thioxanthene anti-psychotic
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Clopenthixol
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Thioxanthene anti-psychotic
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Flupenthixol
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Thioxanthene Anti-psychotic
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Butyrophenones contain what moiety
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GABA like..
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Haloperidol
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Butyrophenone anti-psychotic
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Trifluperidol
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Butyrophenone anti-psychotic
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Spiperone
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Butyrophenone anti-psychotic
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Pimozide
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Butyrophenone anti-psychotic
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What do D2 autoreceptors do?
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Inhibit DA release.
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Anti-psychotic mechanism of action is paradoxical why?
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Because as a D2 antagonist they increase DA release and Increase post-synaptic firing. Which seems opposite what you need if excess DA problem.
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Unwanted effects of anti-psychotics due to what pathway?
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Acute Dystonia(reversible,dissapears)
Tardive Dyskinesia (After years, irreversible). Both due to D2 block of nigrostriatal pathway |
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What OTHER side effects do anti-psychotics have
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prolactin,H1 sedation, antimuscarinic(counteracts EPS).
orthostatic hypertension, weight gain, jaundice, blood disorders, urticaria,uv sensitivity. |
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Clozapine
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Atypical anti-psychotic
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Olanzapine
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Atypical anti-psychotic
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Quetiapine
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Atypical anti-psychotic
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Risperidone
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Atypical anti-psychotic
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How to identify anti-psychotics in the lab
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Conditioned avoidance test. Antipsychotics impair the test.
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Lithium
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Mood stabiliser
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Carbamazepine
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Mood Stabiliser
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Sodium Valproate
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Mood stabiliser
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Gabapentin
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Anticonvulsant
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Lamotrigine
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Anticonvulsant
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Topiramate
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Anticonvulsant
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Nimodipine
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Ca2+ antagonists
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Verapimil
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Ca2+ antagonists
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How does lithium work
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Increased IP3/DAG stabilises membrane via NA/K ATPase
Inhibits GSK3 a transcription factor. CELLS MORE DEPOLARISED |
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ADME of lithium
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no plasma binding, no metabolising simply urine. t1/2 of 14-30 hours.
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Carbamazepine
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anti-epileptic, disrupts faulty NA,DA and 5-HT transmission
used as mood stabiliser. liver enzymes self induces |
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Sodium Valproate
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Developed as anti-epileptic
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