Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
163 Cards in this Set
- Front
- Back
|
How is histamine formed
|
through the decarboxylation of histidine
|
|
|
Where is histamine stored
|
as an ionic complex with heparin in mast cell grandules in high concentration
|
|
|
What is the gerneral sturcutre of Histamine H1 antagoinsts
|
2 aromatic rings, linked though a short chain to a tertiary amine
|
|
|
What is basic sturcture of ethanolamine, and 1st name
|
2 aromatic rings attached to a carbon an either oxygen atom--Diphendyramine
|
|
|
What results in a 2-fold increase of potency
|
Para halogenation
|
|
|
What does para halogenation induce in an ethanolamine
|
chiral carbon atom, reduces the effective dose and anticholinergic side effects
|
|
|
What is the basic structure of ethylenediamines
|
2 aromatic groups attached to a nitrogen, and short chain attached to another nitrogen
|
|
|
Does all antihistaminic activity reside in one enantiomer
|
YES
|
|
|
What is general structure of propylamine
|
Two aromatic rings attached to a proply and amine
|
|
|
What is the generaly sturcutre of a H1 antagoinst piperazine
|
2 aromatic rings attached to a carbon that is attached to a piperazine
|
|
|
What are requirements for activity of pehnothazine antihistamine
|
branched 3 carbon chain, makes chiral carbon-entanioselecitve makes it have antihisamintic activity
|
|
|
What is an example of a phenothzaine
|
prometazine
|
|
|
What is an example of a piperazine
|
Meclizine
|
|
|
What are main classes of hismtaine H1 antagoinsts
|
Enaolamine, etyhlenediamines, proplamines, piperazines, and phenothiazines
|
|
|
Terfenadine bulit to toxic levels when administered with
|
miconozole b/c both metabolized by CYP 3A4
|
|
|
What are H2 antihistamine used in the treatment of
|
gastirc ulcers, and GERY, decrease secretion of gastric acid
|
|
|
What are H1 antihistamine used in the treatment of
|
allergic responses
|
|
|
Where does the secretion of gastric acid occur
|
at the level of the paritel cell, dependent on ATPase pump
|
|
|
What does tautermization do the histamine H2 receptor
|
tautomerization moves a protom from the donor to acceptor site on TM5--ONCE tautomer occurs, NO longer affinity for receptor
|
|
|
Cimetidine an H2 antagoinst what are the sturctural requirements
|
Imidzole ring substituted with CH3, a 4 atom side chain with a sulfur, and guanidine
|
|
|
What is benefits of Cimetideine having Nitrile on guanidine
|
Nitilre decreases basicity, making cimeditine neurtral, and unable to under tautomerization and be inactive
|
|
|
Cimeditidein binds weakest of all H2--
|
YES
|
|
|
Omprerazole does what
|
irrversbily inhbits gastic proton pump
|
|
|
Does omeprazole require a low ph to work
|
YES--acid triggers ompemprazoles rearrangment,
|
|
|
Steps of omeprazole
|
Absorped in stomach enters ciruclation, paritions in cytosol, in stomach acid rearragnes and more sulfonamide and dissulifide linakages
|
|
|
What does Antithrombin III do normally in cells
|
Binds to thrombin and Xa inactivates it, and prevents clotting
|
|
|
What does Thrombin+ Antithrombin III + Heparin
|
Heprain binds to Antithrombin III causing a confromational change which RAPIDLY interacts with thrombin and Xa and prevents from clotting
|
|
|
Must heparin have a high moecular weight to activate antithrombin
|
YES
|
|
|
Herparin is synthetzied in the liver, and is a polyemr of
|
glucosamine and glucuronic acid-sulfated at many sites
|
|
|
What are charactrictics of Herparin
|
a poly-anion always ionized, is water soluble and not orally absrobed (IV or IM)
|
|
|
Heparin usually exists as
|
a pentasaccharide complex that binds to AT III
|
|
|
Are-low moecular weight haprains more selective
|
YES
|
|
|
What does Fonadparinux do
|
mimics the required pentasaccharid for AT-III activation
|
|
|
What makes heparin poorly bioavailable
|
High MW and ionic changes, and the instability of polysaccarides in gut
|
|
|
What can increases the stability of a polysaccaride as seen in Fondaparinux
|
terminal methyl acetal increases sugar stability
|
|
|
Beta linkages are alwasy
|
UP
|
|
|
What are oral anticoagulants
|
warfarin, and idanediones
|
|
|
What do Clotting facts 2, 8,9,10 require to be functionally active
|
post-translational modification of glutamic acid...which undergoes carboxylation to be functionally active
|
|
|
The post-translation carboxylation of clotting factors is
|
Vitamine K Dependent
|
|
|
Vitamin K-is a napthoquinione capable of
|
redox reactions via election acceptace and elecrong donation
|
|
|
How is glutamic acid residues undero carboxylation
|
REDUCED Vitamin K, that b/c oxidzied vitamin K epoxide
|
|
|
What does Warfarin inhibts
|
inhibts that reduction of vitamin K epoxide, adn oxidized Vit K+
|
|
|
Warfarin is a
|
coumarin derivates specially 4-hydroxycoumarin
|
|
|
What are coumarin derivaties
|
water-insoluble lactones
|
|
|
What makes warfarin water soluble
|
4 hydoxy--must be there helps with solubility
|
|
|
Warfarin is marketed as a racemate, however with is the active enantiomer
|
S (warfarin)
|
|
|
Does Warfarin form a sodium salt
|
YES
|
|
|
What is the R enantiomer of warfarin less active
|
it is metabolized by many enzymes
|
|
|
What makes warfarin so acidic
|
due to resonance stabilization of at C-3
|
|
|
Inadanediones work like
|
warfarin, but are seldom used due to toxciity
|
|
|
Is prontosil is reduced to
|
sulfanilamide--THE ACTIVE drug, by hepatic reduction
|
|
|
Sulfonamides also function as
|
anti-metabolites in susceptible orgainsm
|
|
|
What do sulfonamides do
|
compete with para-aminobenzoic acid in the biosynthesis of THF
|
|
|
Which bacterica are not suspcetible
|
bacteria that can utilize pre-formed THF
|
|
|
Where do bacteria get folic acid
|
ONLY FROM SYNTHESIS
|
|
|
What is pka of most sulonamides
|
pka between 6-8
|
|
|
What makes sulfonamides weakly acidic
|
the strong withdrawing group SO2
|
|
|
Because of large dose and limitied solubility of the unioniezed drug some sulfonamides can
|
crystallize unless adequte fluid is maintained
|
|
|
Sulfonamides are metabolized by
|
N-4 acetylation
|
|
|
Active sulfonamides must maintain
|
electronic similarity to para-aminobenzoic acid
|
|
|
What are structure-activity relationships of sulfonamide to be active
|
Amino group must be para
No subsitution of beneze ring Other aromatic rings DO not work Modification of N4 decreases activity |
|
|
What is only poritoin of sulfonamide that can be varied with sucess
|
N1 subsitients
|
|
|
What is the pka of Sufisoxazole
|
Pka 5- has a negative charge at ph 7.4
|
|
|
How are sulfonamides inactivated
|
N4 acetylation
|
|
|
How do you make sulfisoxazole a water soluble tasetless pediartic suspension
|
add an acetyl to N1
|
|
|
N1 acetylation does what
|
makes pediatric soultion
|
|
|
Is adeuqate fluid intake required for sulfamethoxazole
|
YES
|
|
|
What is a topical for burns of sulfisoxazole
|
Silver sulfadizine
|
|
|
What is solution for the eyes with a perfect pH of 7.4
|
Sulfacetamine
|
|
|
Some sulfonamides are chemically incompatibile with
|
urinary disinfectant madelamine
|
|
|
What does sulfonamides are chemically incompatible with mandelamine and form
|
insoluble products upon reaction with formadelhyde and ammonia
|
|
|
What do PBP's control
|
cell shape as cells divide, inhibition can be fatal
|
|
|
Penicilin is a sturtural analog of
|
D-Alanaine, D-Alanie resuide of peptidogltcan
|
|
|
What do pencillins do
|
the reactive beta-lactam alkylates the PBP and is NOT REVERSIBLE
|
|
|
Penicillins are derivates of
|
6-aminopenicllanic acid
|
|
|
What makes B-lactam reactive
|
b/c of ring strain and NO amide resonance
|
|
|
Penicllins be be rapidly inactivated by
|
B-lactamasases and by exposure to an acid environment
|
|
|
How are natual penicllin made
|
by fermenatation
|
|
|
Semi-synthetic pencillina are made by
|
amidation of fermentation dervied 6-aminopenicllanic acid with an acid chloride
|
|
|
Pen-G is too actid senstive for oral administration unless
|
compounded with an excess of K+ carbonate for local buffering
|
|
|
Sustained release preparation of Pen-G are derived from the water-INSOLUBLE salts
|
Procaine and Benzathine Pencillin G
|
|
|
How are Pen-G + Procaine and Pen-G adn Benzathine administered
|
intramuscularly
|
|
|
How would you make an acid-resistant pencillin G
|
an oxygen or nitrogen at the benzyl position of pencillin G---ampicillin or Pen V
|
|
|
How would you make a lactamase-resistant pencillin
|
Shorteing side and adding ortho-methoxy substituents
|
|
|
How would you make an acid resistant and lactamase-ressiatnt agents
|
shorten side chain, make naphelen ring, and 1 ortho methoxt
|
|
|
What is a competiive lactamse inhibitior
|
clavulinic acid
|
|
|
What is clavulinic acid added to
|
ampicllin
|
|
|
How do lactam anitbiotics attack gram-negative
|
lactam enter the cell through PORIN channel
|
|
|
The drugs that enter the porin channel of gram-negative mimic
|
compounds which the organism normally transports into the cell
|
|
|
How can you make a broad-spectrum anitbiotic orally bioavailable (carbenicllin)
|
conversion to an indanyl ester
|
|
|
Ampicillin and Amoxycillin have a brader spectrum of activity
|
YES
|
|
|
What does ampicillin form that makes absorption irractic
|
zitterion
|
|
|
How would you improve the oral abosoprtion of ampicllin
|
by adding an OH to para position of aromatic ring
|
|
|
Oral bioavailbity of carbenicllin is improved by
|
conversion COOH to indanyl ester
|
|
|
Oral bioavialbility of ampicllin can be imporved by
|
Adding OH-amoxyxillin
or carboxyl modifcation |
|
|
What is a pro-drug of ampicllin
|
Becampicllin--hydrolzyed by esterases
|
|
|
What can improve SPECTRUM of activity of ampicillin (parental ONLY)
|
N-extension of ampicillin
|
|
|
What is generic strucuture of cephalosporins
|
7-aminocephalosporanic acid
|
|
|
The ester of cephalosporins is responsbility for its instability how is this overcome
|
conversion of the ester to a methyl group
|
|
|
What are are areas of modification of cephlosporins that are lactamase resistant
|
7-alpha meth-oxy
and syn methoxyimino group side chain |
|
|
Is only one syn-isomer active
|
YES only SYN--facing large group
|
|
|
How is the spectrum of activity of cephalosprons increased
|
adding a 5-memember heterocycle
|
|
|
What do monobactams demonstrate
|
that are ring is not needed for action
|
|
|
What is tetracycline derived from
|
naphtacene (4 membered rings)
|
|
|
What is the number system of tetracycline
|
LOOK
|
|
|
How many areas does tetracycline have of acid-base functionallity
|
4 areas
|
|
|
What are the 4 acid-base properties of tetracycline
|
3-0H ionized
4-dimethlyamino PROTANTED Phenolic 10-NOT ionized 12-OH slighty ionized at ph 7.4 |
|
|
How many stereocenters in tretracycline
|
5
|
|
|
Tetracyclines are very reactive what 4 things happens
|
1. Epimerization of C-4
2. Basic condition to isotetracyline 3. Acidic condtions to anhyddrotetracycline 4. Chelation |
|
|
Are both isotetracyline and anhydrotetracyline inactive
|
YES
|
|
|
How can you improve chemical stability of tetracycline
|
removing C-6 OH
|
|
|
What are impromvents to C-6 OH
|
Adding methyl, or double bond to methyl, ketone, or nothing
|
|
|
What are macrolides
|
12-16 carbon cyclic esters and glycosidically linked sugars
|
|
|
What composes erythromycin
|
Eryhtronolide and two sugars
|
|
|
What happens to erythromycin in acidic environment
|
intramolecular hemiketal and ketal formation (inactive)
|
|
|
Is the ketal product hepatoxic
|
YES
|
|
|
What are methods to improve oral bioavilablilty of Erythromycin
|
enteric coding
esterfication of desosamine salt formation with desosamine |
|
|
What does enteric coating do in PH of 2
|
water insoluble
|
|
|
What happens when enteric coating enters small intesting with pH 4-5
|
coating ionizes, coats disintegrates, and esterases
|
|
|
True enteric coating (not film coating) extends
|
the lifetime of erythromycin in gut
|
|
|
Where does steric acid bind on erthyromycin
|
desosamine dimethylamine group
|
|
|
What are 2 ways to improve oral bioabiality of eryhromyinc by desosamine
|
1. (Salt)--Steric acid
2. Propinate ester 20% absorption 3.Ethysuccinate (55%) hydrolyzed |
|
|
What are 2 drug modifications of erthyromycin
|
Axithromycin, and clarirthomycin
|
|
|
What are modification to clarithromycin
|
conversion of 6-OH to methyl ether
|
|
|
What are modificaiton to make azithromycin
|
add a N-methyl and remove carbonyl
|
|
|
What effects of cardiac glycosides on the heart
|
have a positive intropic action on heart (contractility)
|
|
|
The rings of the steriod system can be joing in cis or tran ring juctions, most endogenous steriods are
|
all trans
|
|
|
What is required for Cardiac glycoside activity
|
1. Steriod nuclues
2. Cis A/B jun 3. Cis C/D jun 4. 3-Beta OH 5. 14-Beta OH 6. 17 Butenolide |
|
|
Can other hydroxyl sustiutent be present of cardiac glycosdie acitivty
|
YES
|
|
|
What does more hydroxl group tha than needed do
|
makes really powerful
|
|
|
Do all cardiac glycoside contain cis A/B and Cis C/D junctures
|
YES
|
|
|
Increasing the nubmer of free OH's does what
|
decreases oral dose absorbed (8 carbons worst)
|
|
|
What is different about the ring numbering of steriods
|
have C-18 and C19
|
|
|
What are chemcial modifcation of steriods
|
1. Increase lipid solubility
2. Increase water solublility 3. Decreases metabolic inactivation |
|
|
How do increase testosterone orally bioavailabity and make SR formulation
|
Add 17 alpha methyl
add ester |
|
|
If you increase the lipid solubility of testorone to SR, how must you deilver it
|
imtra-muscularly
|
|
|
How would you increase the lipid solubility of tramicinolone, and water solubility
|
a ketal acetone, or add sucinate
|
|
|
What is the natural glucocorticoid/anti-infammoatyr
|
hydrocortisone
|
|
|
What is the natural mineralocorticoid
|
aldosterone
|
|
|
How is hydrocortisone synthesized
|
heptatic reduction of cortisone to hydrocortisone
|
|
|
How do you convert cortisone to a mineral corticoid
|
reduce ketone make OH--hydrocortisone
|
|
|
What is required for anti-inflammaotry activity
|
1. Pregane nuclues
2. C-3 carbonyl 3. 4,-5 double bond 4. Oxygen at C-11 5. 17 dihydroxy keto |
|
|
How do you make a mineral corticoid agent (aldosterone) from glucocorticoid
|
removed C-11 oxygen
|
|
|
What increases mineral corticoid activity 800-fold over cortisone
|
9-ALPHA Fluco
|
|
|
What are modification of cortisone that increase life-time of drug
|
methyl to C-6
|
|
|
What is triamcinolone
|
glucooticoid
|
|
|
What is more potent and less toxic than cortisone
|
2 double bonds
|
|
|
How can one elminated the mineralcorticoid activity by 9-alpha-F substituent?
|
BY a 16 ALPHA or BETA substituent
|
|
|
Estradiol is rapidly degraded to what after oral adminsitration
|
estrone or estriol (ketone)
|
|
|
What makes estradiol suitable for ORAL administration
|
17 ALPHA-- ethinyl estradiol
|
|
|
Is a steriod nucleus requied for estrogen acitivty,
|
NO----only only cardiac glycosides and gluco and mineral corticoids
|
|
|
How many stereocenters does cortisol have
|
6
|
|
|
How does progesterone differ from testosterone
|
by only 2 carbons
|
|
|
Draw the 2 C-17 subsitent that are equivalent with respect for agoinsts activity of progesterone
|
DRAW
|
|
|
What increases progesterone activity x10
|
19--Beta H
|
|
|
HOw would increase oral bioavailability of progesterone (exceptionall potenent)
|
Alpha ester to C-17, adding alpha 6 methyl
|
|
|
Testosterone is metabolized to active agent how
|
removal of double bond
|
|
|
How does one removed androgenic activity
|
Remove 19 methyl
Add a 17 Alpha ethyl |
|
|
Is testosterone both an anabolic steriod and a testosterone
|
YES
|
|
|
How do you make a SR testostersone
|
add 10 carbon ester
|
|
|
How do you make a orally bioavilable testosterone
|
add 17 alpha methyl
|
|
|
How do you make testosterone--with only ANABOLIC activity
|
add 17 ethyl subsitituent
|
|
|
How would you make progesterone inactive
|
adding a 17 alpha OH
|
