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121 Cards in this Set
- Front
- Back
Histamine is stored in _________ of _______ cells
|
Granulocytes
Mast |
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Histamine is highly _______ small molecule
|
polar
|
|
Histidine is de________ to produce histamine
|
Decarboxylated
|
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Histamine exists in the body as 70% ______ 30% ______ based on which nitrogen of the imidazole is protonated
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70% tele (distal N)
30% pro |
|
pka of ethylamino portion of histamine is ____ while the imidazole nitrogen portion is __
|
ethylamino 9.4
imidazole N 5.8 |
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At physiologic pH histamine exists as a __________ species, whereas at stomach pH it is _________
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monocationic
dicationic |
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Dicationic histamine has affinity for ____ receptors
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H-2
|
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H-2 antagonists have these properties to compete against dicationic histamine
|
heterocyclic species with increased lipophilicity but additional polarity
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Histamine is metabolized by
s-adenosyl methionine (_________) or by _________ and __________ |
methyltransferase
oxidative deamination + aldehyde dehydrogenase |
|
Less sedating H-1 antagonists are characterized by increased ________
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polarity
|
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gastric ulcers form at these areas while duodenal ulcers localize at the duodenum
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fundus, corpus, pylorus, antrum
|
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peptic cells produce this proenzyme
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pepsinogen
|
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vagus nerve stimulation of ___ receptors indirectly increases ________ cells release of histamine
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M1
endrocrine |
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_________ cells produce HCl in the stomach
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parietal
|
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HCl provides the ideal pH 2 to convert ________ to _______ allowing for the breakdown of protein in the stomach
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pepsinogen - pepsin
|
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_________ cells line the wall of the stomach with mucin and also releases ________
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pyloric
bicarbonate |
|
Therapeutic areas to treat peptic ulcers
|
Buffering Agents
H2 antagonists Anticholinergics Proton Pump Inhibitors Cycloprotective agents |
|
Antacids work to convert strong acids to _________ via reaction with the salt of a _______
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weak acid
|
|
HCl + NaHCO3 ----->
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NaCL + (H2CO3) ---> H2O + CO2
|
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Common cations for salts of weak acids
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Na
Mg Ca Al |
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Systemic considerations of sodium salts
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Very soluble - absorption
systemic alkalosis urine alkalinization |
|
Though sodium bicarbonate is often used as a buffering agent (antacid) it is detrimental to peptic ulcer disease because
|
Conversion into CO2 causes bloating
Rebound acidity due to induction of HCl secretion |
|
Mg salts can cause ________
Al salts can cause ________ Mylanta combines both salts to offset these effects |
Mg - diarrhea
Al - constipation |
|
A decrease in the basicity of the urea-like group on H-2 antagonists will ________ potency
|
increase
|
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Cycloprotective agents work by
|
PGE1 derivatives increase mucin secretion
Mimick mucin with non-reducing sucrose |
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Phenbenzamine
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1st Gen H-1 Antagonist
|
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Diphenhydramine (Benadryl)
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1st Gen H-1 Antagonist
|
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Pyrilamine (Nisaval)
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1st Gen H-1 Antagonist
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Chlorpheniramine (Chlortrimeton®)
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1st Gen H-1 Antagonist
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Brompheniramine (Dimetane®)
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1st Gen H-1 Antagonist
|
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Triprolidine (Actifed®)
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1st Gen H-1 Antagonist
|
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Cyclizine (Marezine®)
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1st Gen H-1 Antagonist
|
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Chlorcyclizine
|
1st Gen H-1 Antagonist
|
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Meclizine (Antivert®)
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1st Gen H-1 Antagonist
|
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Hydroxyzine (Atarax®)
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1st Gen H-1 Antagonist
|
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cetirizine (Zyrtec®)
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2nd Gen H-1 antagonist
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Clemizole (Allercur®)
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1st Gen H-1 antagonist
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Phenthiazine
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1st Gen H-1 antagonist
|
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Promethazine (Phergan®)
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1st Gen H-1 antagonist
|
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Trimeprazine (Temaril®)
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1st Gen H-1 antagonist
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Pimethixene
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1st Gen H-1 antagonist
|
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Methixene
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1st Gen H-1 antagonist
|
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Cyproheptadine (Periactin®)
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1st Gen H-1 antagonist
|
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Azatadine (Optimine®)
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1st Gen H-1 antagonist
|
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Terfenadine (Seldane®)
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2nd Gen H-1 antagonist
|
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Fexofenadine (Allegra)
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2nd Gen H-1 Antagonist
|
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Acrivastin (Semprex®)
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2nd Gen H-1 Antagonist
|
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Astemizole (Hismanal®)
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2nd Gen H-1 Antagonist
|
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Cetirizine (Zyrtec®)
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2nd Gen H-1 Antagonist
|
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Loratadine (Claritin®)
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2nd Gen H-1 Antagonist
|
|
Cromolyn
|
Miscellaneous Antiinflammitory
|
|
PPi's are effective in treating this type of stomach cancer
|
Alison-Zolinger
|
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Omeprazole (Prilosec®)
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Proton Pump Inhibitor
|
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Lansoprazole (Prevacid®)
|
Proton Pump Inhibitor
|
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Esomeprazole (Nexium®)
|
Proton Pump Inhibitor
|
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Pantoprazole (Protonix®)
|
Proton Pump Inhibitor
|
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Cimetidine (Tagamet®)
|
H2 Blocker
least potent - 400mg CYP inhibitor kills sperm |
|
Ranitidine (Zantac®)
|
H2 Blocker
intermediate potent - 150mg |
|
famotidine (Pepcid®)
|
H2 Blocker
most potent - 20mg |
|
nizatidine (Axid®)
|
H2 Blocker
intermediate potent - 150mg |
|
H2 blockers shouldn't be taken with _________ for peptic ulcers
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Antacids
|
|
misoprostol (Cytotec)
|
Cycloprotective Prostaglandin
short acting contraindicated in pregnancy |
|
sucralfate (carafate)
|
Cycloprotective Agent
non-reducing sucrose w/ aluminum sulfate |
|
Most common ions involved in nerve signal transmission
|
K
Ca Na |
|
K is usually found _______ nerve membrane while Ca and Na are normal ________
|
inside
outside |
|
The outer layer of the sodium channel is rich in negatively charged ________ residues
|
Glutamate
Aspartate |
|
The middle of the sodium channel is highly lipophilic due to ________ residues
|
Tryptophan
Phenylalanine |
|
Local anesthetics are commonly used for:
|
Dental procedure
Rectal hemorrhoids Topical burns / itch Sore throat Eye irritation Inflitration anesthesia |
|
Why are injections of local anesthetics often co administered with epinephrine?
|
Epinephrine increases duration of action and decreases cardiotoxic effects by constricting movement away from the area of injection
|
|
Cocaine
|
Local anesthetic: ester
not used - abuse potential |
|
Procaine (Novacaine®)
|
Local anesthetic: ester
dental - short acting 15min 2hrs w/ epinephrine |
|
Why is procaine contraindicated with sulfa antibiotics?
|
Procaine is an ester injection anesthetic, metabolism by esterases will increase PABA. Sulfa antibiotics work by decreasing PABA to prevent DNA synthesis of purines.
|
|
Tetracaine (Pontocaine®)
|
Local anesthetic: ester
1-3hr |
|
Proparacaine (Alcaine®, Ophthetic®)
|
Local anesthetic: ester
eye solution |
|
Cyclomethycaine (Surfacaine®)
|
Local anesthetic: ester
rectal cream 2-3hr |
|
Dibucaine (Nupercaine®)
|
Local anesthetic: benzamide
burns,hemorrhoids t1/2 - 5hr |
|
Lidocaine (Xylocaine®)
|
Local anesthetic: anilide
t1/2 - 1-1.5hr |
|
Anilides are _____ stables toward HYDROLYSIS by AMIDASE than amides
|
less
|
|
Mepivacaine (Carbocaine®, Polocaine®)
|
Local anesthetic: anilide
t1/2 = 2hr |
|
Bupivacaine (Marcaine®)
|
Local anesthetic: anilide
t1/2 = 3-4hr |
|
Etidocaine
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Local anesthetic: anilide
|
|
Prilocaine
|
Local anesthetic: anilide
|
|
Pramoxine (Tronothane®)
|
Local anesthetic: ether
|
|
Dyclonine (Dyclone®)
|
Local anesthetic: ketone
oral solution |
|
N__ of Guanine residues is a very _______ site for alkylating agents to bind.
|
N7
neutrophilic |
|
When an alkylating agent (electrophile) binds to N7 on a guanine residue it acts as an ______ _____ converting guanine into its ______ form.
This form of guanine resembles adenosine. |
electron sync
lactim |
|
Alkylating agents were designed on the basis of autopsies from soldiers exposed to nitrogen gas.
A reduction in cancer cells was seen in autopsies. In order to decrease toxicity for possible treatment, Sulfur was replaced with ______ because it is more _________ decreasing its reactivity. |
nitrogen
electronegative (less electrons available for arizidine) |
|
The addition of electron withdrawing groups to alkylating agents would ________ toxicity
|
decrease
|
|
In order to make alkylating agents more selective, _________ can be added.
Melphalan contains ________ |
amino acids
phenylalanine |
|
Cyclophosphamide acts as a prodrug because ________ withdraws electrons to a degree that will inhibit activity until it is metabolized in the ________
|
phosphate
liver |
|
Cyclophosphamide
Cancer cells use _________ to break down _____________ into acrolein and active metabolite. |
B-elimination
4-hydroxycyclophosphamide |
|
Cyclophosphamide is less toxic to normal cells (excluding bone marrow) because they can ________
4-hydroxycyclophosphamide into __________ for excretion. |
oxidize
carboxycyclophosphamide |
|
Acrolein is toxic to bladder cells as they contain _______ groups. Mesna is used more often with _________ because it requires a higher IV dose due to its low potency, thus producing more acrolein.
|
sulfhydryl groups
Ifosphamide |
|
Thiotepa was designed to increase selectivity to cancer cells as they tend to be more ________ charged.
|
negatively
|
|
Polyglutamate synthetase will work to ________ cellular entry of folic acid
|
maintain / increase
|
|
This 1st generation H1 antagonist has high anticholinergic effects, and is formulated as a _____ salt
|
Diphenhydramine (Benadryl)
HCl salt |
|
Chlorpheniramine and Bromopheniramine are ____ sedating than other 1st gen H1 antagonists, and have ___ t1/2 due to blockade of _______
|
less
longer para-hydroxylation |
|
Triprolidine (Actifed) contains a double bond which increases rgidity. This would ______ conformational change and ____ in binding.
|
prevent
aid |
|
Most (not all) H1 antagonists ending in "zine" indicate a _______ nucleus which tends to target the ____
|
piperazine
CNS |
|
Meclizine ( Antivert) contains a piperazine and is often used for _______
|
motion sickness
|
|
This 1st gen H1 antagonist contain piperazine has high sedative effects and can be used as a tranquilizer.
|
Hydroxyzine (Atarax)
|
|
Aminobenzimadazole with a pyrolidine side chain. Placing two rings out of planes with eachother increased its binding to H1
|
Clemizole (Allercur)
|
|
These 1st gen H1 antagonists are thiazine-tricyclics and can cause sedation, hallucinations.
|
Phenthiazine
Promethazine Trimeprazine |
|
This 2nd gen H1 antagonist exists as a racemic mixture
|
Cetirizine (Zyrtec)
|
|
Cromolyn requires multiple daily dosing and must be given ______ to allergic response.
|
Prior
|
|
Loratidine (Claritin) is metabolized into ________ which is metabolized into active metabolite with ______ properties.
|
desloratidine (clarinex)
zwitterionic |
|
Order of decreasing electron withdrawal strength:
A. -SO2NH B. -CN C. -NO2 |
A > C > B
|
|
Lidocaine (Xylocaine) is hydrolyzed by ______ into _____ + glycine
|
amidase
xylene |
|
Thymidine synthesis (de novo) requires __________ as co-factor which will convert back to ______ in the process.
|
methylene THF
DHF |
|
Methotrexate inhibits _______ which will decrease the conversion of _____ into dTMP by ______ ______. Build up of dUMP will convert back to _____ and integrate into DNA. Repair mechanisms will destroy DNA.
This destruction is termed _______ |
DHFR
dUMP thymidylate synthase dUTP "Thymine less death" |
|
Leucovorin works to increase _______ synthesis in normal cells decreasing ____ toxicity.
|
thymidine
MTX |
|
5-FU and 5-UDR directly inhibit ________.
Capecitabine is a prodrug of 5-FU that resembles ______ converted by _________, _____, and ______ |
thymidylate synthase
5' deoxy - cytidine esterase CDA (cytidine deaminase) TP (thymidine phosphorylase) |
|
Capecitabine:
Thymidine phosphorylase hydrolyzes _________ bond between 5' deoxyribose and _______ |
glycosidic
5-FU |
|
Ara-C
|
Analog of cytidine with an aribose sugar.
conformation resembles deoxyribose - phosphorylation leads to chain termination |
|
Ara-C can be acted on by _____ to create an inactive metabolite _____ that cannot incorporate into DNA.
|
CDA (cytidine deaminase)
Ara-U |
|
Gemcitabine
5-Azacytidine 5-FU FUDR Capecitabine Ara-C |
Anti-metabolite: Pyrimidine Antagonists
|
|
Triazine analog of cytidine metabolized to the triphosphate form to integrate into RNA. Also blocks DNA _________.
|
5-Azacytidine (Vidaza)
methylation |
|
_________ contains a geminal carbon and can be activated via ______, deactivated via ______, and also acts as a _______ _______ inhibitor.
|
triphosphorylation
CDA ribonucleotide reductase |
|
True or False
6-MP + 6-TG substrates for xanthine oxidase |
False
only 6-MP |
|
6-MP
6-TG Azathioprine Fludarabine Cladribine Pentostatin |
Anti-metabolite: Purine Antagonists
|
|
Fludarabine Phosphate and Cladribine are resistant to ______ and inhibit DNA replication.
|
CDA
|