Term
What type of receptors are M receptors? What type of receptors are N receptors? |
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Definition
M receptors are G-coupled protein receptors N receptors are ion channel receptors. They include alpha, beta, gamma, delta, and epsilon. |
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Term
Discuss Ach's structure. Include the parts that cannot be modified. |
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Definition
| Ach has an acyloxy group, an ethylene group, and a quaternary ammonium group. The molecule must contain a Nitrogen atom that is capable of bearing a positive charge. The alkyl groups on the N should be no larger than methyl groups. The acyloxy group must contain the ester oxygen. The ethylene group is required too. |
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Term
How do methacholine, carbachol, and bethanechol last longer than Ach? What receptor is bethanechol specific for? |
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Definition
| Methacholine has a methyl group added to it that makes it more difficult to be hydrolyzed. Carbachol has a carbamyl group added (NH2 replaces CH3) that completely inhibits hydrolysis. Bethanechol has both a methy group and a carbamyl group added. Bethanechol is specific for M receptors. |
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Term
| Out of nicotine, muscarine, pilocarpine, oxotremorine, and arecoline, which one is synthetic? Which one would not pass the bbb? |
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Definition
| Oxotremorine; the others are natural alkaloids. Muscarine has a quaternary ammonium charge that prevents it from passing the bbb. |
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Term
T or F Irreversible cholinesterase inhibitors can be reversed. |
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Definition
| True, it can be done by cholinesterase reactivators like pralidoxime, but it has to be done before aging occurs. |
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Term
| What is another name for irreversible cholinesterase agents? Why are they called this? |
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Definition
They are called organophophates b/c a phosphorous has replaced a C and it has become a phosphamate. |
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Term
T or F Pralidoxime could reverse the effects of sarin |
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Definition
False, b/c sarin is in the CNS and pralidoxime can't enter the CNS, b/c it's charged. |
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Term
If a drug had 2 quaternary amine groups, what kind of drug would it most likely be? |
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Definition
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Term
What class do pirenzipine, telenzepine, methoctramine, and gallamine belong to? Which receptors are each of them selective for? |
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Definition
| They're selective M antagonists. The zipines are selective for M1 and the amines are selective for M2. |
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Term
| What do the following PGs have on C-9 and C-11: PGE, PGF, and PGA? What else is unique about PGAs ring structure? |
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Definition
PGE has a keto group at C9 and an -OH at C11. PGF has -OH at C9 and -OH at C11. PGA has a keto group at C9 and a dbl bond b/w C10 and C11. |
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Term
Which Carbon do all PGs have an OH group on in the alpha position? |
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Definition
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Term
| If a PG has 3 unsaturations, b/w which Carbons did the first, second, and third unsaturation occur? |
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Definition
| The first unsaturation occurs b/w Carbons 13 & 14. The second unsaturation occurs b/w Carbons 5 & 6. The third unsaturation occurs b/w Carbons 17 & 18. |
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Term
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Definition
| PGF means it has OH groups on C9 and C11. The 2 means there are unsaturations b/w C13 and C14 and b/w C5 and C6. The A means the OH group on C11 is in the alpha position. You won't always see the A, since PGE and PGF are the only PGs we know that have an OH on C11. |
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Term
Explain the conversion of AA to PGs and thromboxane. |
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Definition
| COX-1 and COX-2 cyclize the cyclopentane ring & put a hydroperoxide group on C15. Peroxidase then removes an oxygen from hydroperoxide to form an OH group on C15. Different groups are then added to the cyclopentane ring to determine the type of PG. Thromboxane will have a 6-membered ring. |
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Term
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Definition
| Cell-membrane phospholipids |
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Term
Why don't we want NSAIDs to block COX-1? |
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Definition
| B/c we need COX-1 to protect the stomach lining to prevent ulcers. |
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Term
| Which COX enzyme is responsible for pain and inflammation? |
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Definition
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Term
| Structurally, what is different b/w COX-1 & COX-2? |
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Definition
The differences occur at the binding site. COX-1 has isoleucine 523 and COX-2 has valine 523. |
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Term
| How are prostacyclins different from PGs? |
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Definition
The only difference is that prostacyclins have 2 5-membered rings. |
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Term
Explain the steps of PG metabolism? |
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Definition
| First, the OH on the allelic alcohol (a C-OH close to a double bond) at C15 is quickly oxidized to C=0. Next, the double bond b/w C13 and C14 is reduced to a single bond. Then, beta-oxidation begins at C1 (removes 2 carbons at a time). Finally, omega-oxidation begins at C20 after the methyl group is oxidized two times to a COOH. |
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Term
| What are some ways you could increase the half-life of PGs? |
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Definition
You could add a methyl group to C15 to crowd the area and prevent the quick oxidation of the OH on C15. You could also make a pro-drug w/ an ester at C1 and a benzene on C20. You could also make a drug that doesn't have a double bond b/w C13 and C14. |
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Term
| What will the base structure of a steroid look like? |
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Definition
It will have 17 carbons. There will be three 6-membered rings and one 5-membered ring. |
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Term
| How do sterols get their name? |
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Definition
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Term
| What is the difference b/w 5a-cholestane, 5b-cholestane, d4-steroid, and d5-steroid? |
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Definition
5a-cholestane has a trans-trans-trans configuration. 5b-cholestane has a cis-trans-trans configuration. d4-steroid has a double bond b/w C4 and C5. d5-steroid has a double bond b/w C5 and C6. |
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Term
| Give an example of a d5 steroid, a d4 steroid, and a cis-trans-trans steroid. |
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Definition
| An example of a d5 steroid would be cholesterol. An example of a d4 steroid would be the androgens (testosterone and glucocorticoids). An example of a cis-trans-trans steroid would be bile acids and the cardioglycosides. |
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Term
What group of steroids has 18 carbons? |
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Definition
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Term
| What group of steroids has 19 carbons? |
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Definition
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Term
| What group of steroids have 21 carbons? |
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Definition
| pregnanes (eg, progesterone) |
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Term
Explain cholesterol synthesis. How can it be stopped. |
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Definition
| 3 acetyl-CoAs are assembled. HMG-CoA reductase then turns the 6-carbon structure into mevalonic acid. Mevalonic eventually becomes squalene. Squalene eventually becomes cholesterol. All of this can be stopped by inhibiting HMG-CoA reductase. |
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Term
| What steroid is cholesterol converted to right before it decides to be a glucocorticoid or a mineralocorticoid? |
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Definition
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Term
Why is 17a-hydroxylase important? |
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Definition
It puts an alpha OH on C17, making it a glucocorticoid. This is how you distinguish glucocorticoids from mineralocorticoids. |
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Term
| As a class, what must the structure of adrenocorticoids have? |
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Definition
3 6-membered rings 1 5-membered ring A keto group at C3 A double bond b/w C4 and C5 Either a keto or an OH group at C11 |
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Term
How are the adrenocorticoids metabolized? |
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Definition
| 5a,b-reductase can reducethe double bond b/w C4 and C5 (the -H will end up in either an alpha or beta configuration) and dehydrogenase enzymes can reduce the keto group at C3. |
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Term
What substitution (and where) would you make if you wanted to increase glucocorticoid activity several fold? |
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Definition
| You would change the hydrogen on C9 to a F, Cl, or Br. The smaller the halogen, the better. |
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Term
| Prednisolone and cortisol have glucocorticoid features. What's the only difference b/w the two? What indication does prednisolone have? |
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Definition
| Prednisilone has a double bond b/w C1 and C2. Cortisol doesn't. This double bond that prednisolone has allows it to reduce sodium retention. |
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Term
T or F We want low glucocorticoid activity and high mineralocorticoid activity. |
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Definition
False, we want just the opposite; otherwise, there will be a lot of sodium retention. |
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Term
What should be done to increase glucocorticoid activity? What should be done to decrease mineralocorticoid activity? |
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Definition
Add a double bond b/w C1 and C2. Also, add a F at C6 (or at C9). Add a methyl group or an OH to C16 in the alpha or beta position - it doesn't matter. |
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Term
| Why is it important for C11 to have some sort of oxygen functionality (-OH or keto)? |
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Definition
| It's required for the steroid to bind to the receptor |
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Term
| Which group of adrenocorticoid drugs can you increase the life of by adding larger ester groups to C21? |
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Definition
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Term
What would happen if 3b-dehydrogenase was inhibited? What drug inhibits this enzyme? What would happen if 11b-hydroxylase were inhibited? What drug inhibits this enzyme? |
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Definition
You wouldn't have any glucocorticoid or mineralocorticoid activity; Trilostane Cortisol synthesis would be reduced; metyrapone |
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Term
| What enzyme makes 17a-hydroxypregnenolone go toward sex steroids rather than glucocorticoids? |
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Definition
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Term
| Why is androstenedione so important? |
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Definition
| Androstenedione is the precursor for the male and female sex steroids. |
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Term
| Which sex steroids have aromatic A rings? |
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Definition
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Term
| Estradiol has an -OH group on C3 and on C17. What makes these -OH groups different? |
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Definition
| The -OH group on C3 is phenolic, meaning it's ionizable. The -OH group on C17 is aliphatic and it is not ionizable. |
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Term
How are estrogens metabolized? |
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Definition
They first become catecholic estrogens. COMT then alkylates them. If they have an -OH group on C17, they will form glucuronide, sulfate, or glutathione conjugates. This makes the estrogen more water soluble and it will be excreted in the urine. |
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Term
| What is the most potent endogenous androgen? |
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Definition
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Term
Where does androgen metabolism occur? The addition of what functional group inactivates androgens? What are the 2 final metabolites of androgen metabolism? |
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Definition
In the liver An alpha-OH on C3 inactivates androgens. Androsterone and etiocholanolone |
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Term
| What are the structural relationships among estrogens? |
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Definition
aromatic A ring Phenolic -OH at C3 17b-OH or 17b=O distance b/w 2 OH groups 8.55 A planar hydrophobic molecule |
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Term
T or F Any compound that has 8.55 A b/w two -OH groups can have estrogenic properties |
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Definition
| True, an example is diethylstilbesterol |
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Term
| What happens to estrogen activity if you remove the OH group from C3 or C17? What if you epimerize (change the OH from beta to alpha) C17? |
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Definition
You lose activity You lose activity Notice that any time you jack with the distance b/w C3 and C17, you lose activity. |
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Term
| What needs to be done to estradiol to make it more potent orally? IM? |
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Definition
In order to be effective orally, you can add an ethinyl group to C17 to make it ethinyl estradiol. In order to be effective via IM, you could make the estrogen a prodrug by making C3 an ether or C17 an ester. |
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Term
| What do malathion and parathion do? |
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Definition
| They are irreversible cholinesterase agents used to kill insects. |
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