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Winter P1 > Pharm 737 Exam 2 > Flashcards

Pharm 737 Exam 2 Flashcards

1
Q

The process of drug disposition includes what functions?

A

Absorption
Distribution
Metabolism
Excretion

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2
Q

Cytochrome P enzyme controls these functions:

A

Oxidation
Reduction
Hydrolysis

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3
Q

Cytochrome P450s:

A

Heme-containing enzyme responsible for Phase 1 metabolism reactions
Detoxification of foreign pollutants
Regulate Blood Homeostasis

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4
Q

Cytochrome 2Cs

A

Are found most abundantly expressed in human liver

metabolizes 15-20% of prescribed and OTC drugs

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5
Q

CYP3A4

A

most abundantly expressed P450 in human liver

Metabolizes over 120 different drugs

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6
Q

SNP on CYP3A5

A

Creates a non-functional enzyme by introducing an early stop codon, creating a non-functional protein

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7
Q

CYP3A4/5 Regulation

A

requires both pregnane X receptor and Reitinoid X receptor as well as something to dimerize the two in order to activate CYP3A for enzyme production.

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8
Q

SLC and ABC

A

Solute carrier transporter - passive and active transporters that rely on chemical or electrical gradients for transport
ATP-binding Casette - Primary active transporters that are ATP-dependent

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9
Q

Biomarker

A

Gene, Protein, or other change that indicates a biomedical phenotype before that phenotype is clinically apparent.

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10
Q

What is Warfarin used for and how does it work?

A 
The most commonly prescribed anticoagulant for the treatment and prevention of thromboembolic events.
It is a synthetic derivative of coumarin, which was originally developed as rat poison, (class of Vitamin K antagonist), it decreases blood coagulation by interfering with vitamin K metabolism.
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11
Q

Warfarin Metabolism

A

Metabolized by CYP2c9 and inhibits Vitamin K complex (VKORC1). a deficiency in CYP2C9 would result in increased risk of bleeding.
S-warfarin has five times the potency of the R-isomer with respect to vitamin K antagonism

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12
Q

What is Clopidogrel used for and how does it work?

A

Antiplatelet Drug for stent associated thrombosis. (up to 30% of patients do not dispay adequate antiplatelet response to clopidogrel) Metabolized by Cyp3A4

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13
Q

Statins are metabolized by:

A

Are metabolized by CYP3A4

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14
Q

ApoE4 is associated with:

A

An allele within Chromosome 19 that has been associated with late onset form Alzheimer’s disease

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15
Q

Antimicrobial Therapy and G6PD deficiency is

A

G6PD deficiency linked to increased risk of hemolysis.

Individuals taking primaquine reduced their expression of G6PD and developed hemolytic anemia.

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16
Q

N-Acetyl Transferase (NAT2) Polymorphism

A

result in slow acetylators, these polymorphisms may modulate the risk of cancer of lung, bladder, and colon due to NAT2 acetylation of aromatic amines found in tobacco smoke and cooked foods.

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17
Q

Isoniazid pathway

A

NAT2 activates

Hydrolysis leads to excretion

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18
Q

5-Flurouracil (5FU)

A

3rd most commonly prescribed chemotherapy agent.
Single agent activity against colorectal carcinoma.
Activation –> Ribose 5 phosphate creates UMP which isomerized to UDP, interacts with pyrmidine monophosphate kinase to activate. (blocks TS which was proliferating DNA)
Elimination –> Dihydropyrimidine dehydrogenase

19
Q

Acute Lymphoblastic Leukemia

TPMT vs HPRT

A

Thiopurine S-Methyl Transferase (TPMT) competes against HPRT for Mercaptopurine (MP) substrate, which catabolizes MP into methyl-mercaptopurine which results in proliferation of lymphoblastic leukemia

20
Q

Herceptin (Trastuzumab) (Breast Cancer)

A

the first targeted, humanized antibody for treatment of women with HER2 positive metastatic Breast Cancer. The antibodies block HER2 from signaling cell growth

21
Q

Gleevec (Imanitib)

A

Cancer drug which occupies the ATP binding pocket of the kit kinase domain, preventing substrate phosphorylation and signaling. This lack of signaling inhibits cell proliferation and survival.

22
Q

Gene Editing

A

The most successful type of Gene Therapy so far. It uses engineered non-specific nucleases that are fused to sequence specific DNA binding domains.

23
Q

Somatic Gene Therapy

A

The recipient’s genome is changed, but the change is not passed along to the next generation. (cant be used in PCR, would need to use molecular cloning)

24
Q

Germline Gene Therapy

A

The sex cells are changed with the goal of passing these changes to their offspring any genetic changes in the reproductive cells can affect all future offspring of that person. (major ethical issues, not allowed in many countries)

25
Q

CRISP/CAS (Clustered, Regularly interspaced, short palindromic repeats)/(CRISPR-associated systems)

A

RNA based bacterial defense mechanisms designed to recognize and eliminate foreign DNA from invading bacteriophage and plasmids. consists of a Cas endonuclease that is directed to cleave a target sequence by a guide RNA.

26
Q

In Vivo
vs
Ex Vivo

A

in Vivo - delivery system where delivery of genes takes place within the body
Ex Vivo - Delivery system where delivery of genes takes place out of the body, and then cells are placed back in the body.

27
Q

In Vivo Delivery systems

A

utilizes viral vectors, where virus is the carrier of the desired gene. this virus is usually crippled to disable its ability to cause disease. This has proved to be the most efficient method to date.
con: replication defective viruses adversely affect the virus’ normal ability to spread genes in the body.

28
Q

Retroviruses

A

Double stranded DNA copies from RNA genome, they use reverse transcription using reverse transcriptase and RNA. They are derived from the HIV and are being evaluated for safety.

29
Q

Adenoviruses

A

Double stranded DNA genome that causes respiratory, intestinal, and eye infections.
This DNA is not incorpated into genome immediately, and because it isnt replicated, the DNA must be inserted when more cells divide.

30
Q

Ex Vivo Delivery systems

A

utilizes electroporation, liposomes, calcium phosphate, gold bullets (fired with helium pressurized gun), Retro-transposons and Human artifical chromosomes to introduce gene therapy changes.

31
Q

Other non-viral options for Gene therapy

A

Direct Introduction of therapeutic DNA
Liposomes -> creation of artificial lipid sphere with aqueous core, carriers therapeutic DNA through membrane
Chemically linking DNA to molecule that will bind to special cell receptors
Introduction of a 47th chromosome to exist alongside the 46 others

32
Q

Cystic Fibrosis gene therapy

A

Monogenetic therapy, uses a crippled adenovirus that is non-integrating, and replication defective. Only transient expression is observed because adenovirus does not integrate into genome like retroviruses.

33
Q

What is a stem cell?

A

a single cell that can replicate itself or differentiate into many cell types.

34
Q

what precursor can all human body cells be traced back to?

A

Zygote (fertilized egg)

35
Q

what is a totipotent stem cell?

A

A cell in which each cell can develop into a new individual (E.g. cells from early embryos)

36
Q

Pluripotent stem cells?

A

Cells that can form any cell type (some cells of blastocyst)

37
Q

Multipotent stem cells?

A

Differentiated cells that can form other tissue types, limited in what cells they can become (E.g. Hematopoeitic stem cells, Neural stem cells, Mesenchymal stem cells)

38
Q

Embryonic Stem cells

A

Derived from a very early stage in human development
Have the potential to produce all the body’s cell types
Can be harvested from mammals

39
Q

Nuclear Transfer

A

the genetic material from an egg is removed and replaced with the nucleus of a differentiated adult cell. Results in copies or clones of the original adult cell.

40
Q

Reproductive Cloning

A

Uses the same principles of nuclear transfer to create a clone adult organism. In humans, thi is actively discouraged by most in the scientific community (E.g. Dolly)

41
Q

Adult Stem Cells

A

(multipotent stems cells)
found in several organs that need a constant supply of cells, such as blood, skin, and lining of the gut and have also been found in surprising places like the brain.

42
Q

Multipotent Stem cell types

A 
Haematopoietic SC's (Bone Marrow)
Neural SCs (Brain)
Gut SCs (Small Intestine)
Mesenchymal SCs (Bone Marrow)
43
Q

Induced Pluripotent Stem Cells

A

Introduced in a variety of ways including retrovirally, adenoviral, or plasmid transfection to make mature cells behave like embryonic stem cells.

44
Q

Stem Cells Applications

A 
Tissue Repair
Prevention ofHeart Disease
Reduction of Leukemia-Cancer
Repairing Rheumatoid Arthritis
Treatment of Diabetes Type 1

Winter P1 (8 decks)

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