Pharm 737 Exam 2 Flashcards
(44 cards)
The process of drug disposition includes what functions?
Absorption
Distribution
Metabolism
Excretion
Cytochrome P enzyme controls these functions:
Oxidation
Reduction
Hydrolysis
Cytochrome P450s:
Heme-containing enzyme responsible for Phase 1 metabolism reactions
Detoxification of foreign pollutants
Regulate Blood Homeostasis
Cytochrome 2Cs
Are found most abundantly expressed in human liver
metabolizes 15-20% of prescribed and OTC drugs
CYP3A4
most abundantly expressed P450 in human liver
Metabolizes over 120 different drugs
SNP on CYP3A5
Creates a non-functional enzyme by introducing an early stop codon, creating a non-functional protein
CYP3A4/5 Regulation
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.
SLC and ABC
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
Biomarker
Gene, Protein, or other change that indicates a biomedical phenotype before that phenotype is clinically apparent.
What is Warfarin used for and how does it work?
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.
Warfarin Metabolism
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
What is Clopidogrel used for and how does it work?
Antiplatelet Drug for stent associated thrombosis. (up to 30% of patients do not dispay adequate antiplatelet response to clopidogrel) Metabolized by Cyp3A4
Statins are metabolized by:
Are metabolized by CYP3A4
ApoE4 is associated with:
An allele within Chromosome 19 that has been associated with late onset form Alzheimer’s disease
Antimicrobial Therapy and G6PD deficiency is
G6PD deficiency linked to increased risk of hemolysis.
Individuals taking primaquine reduced their expression of G6PD and developed hemolytic anemia.
N-Acetyl Transferase (NAT2) Polymorphism
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.
Isoniazid pathway
NAT2 activates
Hydrolysis leads to excretion
5-Flurouracil (5FU)
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
Acute Lymphoblastic Leukemia
TPMT vs HPRT
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
Herceptin (Trastuzumab) (Breast Cancer)
the first targeted, humanized antibody for treatment of women with HER2 positive metastatic Breast Cancer. The antibodies block HER2 from signaling cell growth
Gleevec (Imanitib)
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.
Gene Editing
The most successful type of Gene Therapy so far. It uses engineered non-specific nucleases that are fused to sequence specific DNA binding domains.
Somatic Gene Therapy
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)
Germline Gene Therapy
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)
