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Drug Toxicity
Drug Toxicity overview
27
Pharmacology
Undergraduate 4
12/09/2010

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Cards

Term
Why is drug toxicity important?
Definition
-know how much of a drug and what the side effects are if certain rxn's occur or overdose
Term
How are toxic metabolites formed?
Definition
-Formed during biotransformation rnx

-epoxide hydroxylases
-monooxgenase
-enzyme involoving conjugation reactions
Term
What happens to a damaged cell?
Definition
-carcinogensis due mutagenesis of DNA

-DNA repair

-detox/excretion

-regulatory responses
Term
What are the regulatory responses of a cell?
Definition
-repair (genetic repair, pro prod., recep. prod.)

-Apoptosis (program. cell death)

-Necrosis (death of cell by chem phys or disease)

-Fibrosis (thick/scarrin of connec. tiss
Term
What is idiosyncratic responses?
Definition
-abnormal or rare activity to a drug/extreme sensitivity
Term
What are the different types of hypersensitivity reactions?
Definition
-Type 1 (IgE)

-Type II (IgG)

-Type III (IgG)

-Type IV (sensitized T-lymphocytes + macrophages)
Term
What is a Type I reaction?
Definition
-immediate reaction

-Ige binding to mast cells

-casuses analphylaxis, hives , bronchoconstirction, shock

-ex. Penicillin
Term
What is a type II reaction?
Definition
-antibody dependent cellular cytotoxicity

-IgG

-neutro., macroph., and NKC

-hemolysis (ex. cefotetan)
Term
What is a type III reaction?
Definition
-immune-complex disease

-IgG

-neutro., macrop., NKC, ROS,

-causes cutaneous vasculitis

-mytomycin C
Term
What is a type IV reaction?
Definition
-antigen assoc. w/ MHC protein on surface of antigen presen. cells

-cytotoxic T lymphocytes, macro. cytokines

-macular rashes and organ failue

-ex. Sulfamethazole
Term
What are some conditions related to pulmonary toxicity?
Definition
-Bronchitis
-Emphysema
-Asthma
-Hypersensitivity pneumonitis
-Pneumoconiosis
-cancer
Term
What are some drugs/chemicals that cause pulmonary damage?
Definition
-amiodarone, cyclophosphamide, methoterexate

-asbestos, chlorine gas, nitrogen dioxide, ozone, phosgene, silica, sulfur dioxide
Term
What is nephrotoxicity?
Definition
-high blood flow

-exposure is two fold (blood on basolateral side, urine on the luminal side)

-Proximal tuble site of toxicity (high P450 +transp. of anions and cations, conc. these chemicals
Term
What are examples of renal toxicants?
Definition
-keflex, cisplatin, cyclosporine A, gentamycin, NSAIDS, ACEI

-chloroform, hexchlorbutadien, mercuric chloride
Term
What is melamine and cyanuric acid? What is its role in renal toxicity?
Definition
-individually, not nephrotoxic

-together, melamine cyanurate precipitate out causes kidney failure in pets/children.
Term
Describe the CNS protrection, susceptibility, and repair from neurotoxicity.
Definition
-BBB protects CNS

-HIGH metabolic rate, blood flow, and lipid content make it susceptible

-neural tissue can not be easily repaired
Term
What are examples of neurotoxicants?
Definition
-cocaine, ethambutol, quinine

-lead, mercury, methanol, organochlorine insecticides
Term
What are examples of peripheral neurotoxicants?
Definition
-doxirubicin, isoniazid, nitrofurantoin

-acrylamide, carbon disulfide, leads, N-hexane
Term
What are some examples of hepatoxicants?
Definition
-APAP, cholorpromazine, estrogens, EtOH, halothane, iosoniazid, nitrofurantoin, phenylbutazone, 6-mercaptopurine

-allyl formate, beryllium, CCl4, vinylidene chloride
Term
What are some examples of hepatoxicants?
Definition
-APAP, cholorpromazine, estrogens, EtOH, halothane, iosoniazid, nitrofurantoin, phenylbutazone, 6-mercaptopurine

-allyl formate, beryllium, CCl4, vinylidene chloride
Term
Describe the hepato protrection, susceptibility, and repair from neurotoxicity.
Definition
-first pass efffect/drug metabolizing enzymes (susceptibility)

-drug metabolizing enzymes (protection)

-regeneration, possible scaring (repair)
Term
Describe the metabolism of APAP and the mechanism of toxicity/
Definition
-Normally Phase II metabolism

-CYP450 enzymes can lead to a toxic intermediate

-can lead to non-toxic form when combined with glutathione or combine with macro molecules--->cell death.
Term
What are some chemicals involved with immunotoxicity?
Definition
-azathioprine, corticosteroids, cyclophosphamide, cyclosporine A, methorexate

-arsenic, benzene, TCDD, lead, organophosphates, ozone, PCBs
Term
What is mutagenesis, teratogenesis, and carcinogenesis?
Definition
-Change in genetic material

-Production of developmental abnormalities

-Cancer -
Term
What is the antidote for APAP?
What is the antidote for atropine?
What is the antidote for benzocaine?
Definition
-N-acetylcysteine (mucomyst)

-physostigmine

-methylene blue
Term
What is the antidote for digoxin?
What is the antidote for morphine?
What is the antidote for (PAH's)?
Definition
-digoxin fab

-naloxone

-none (you are fucked)
Term
what are some common herb-drug interactions?
Definition
-ginkgo biloba + NSAIDs (platelet aggre.)

-Echinacea + APAP (deplete glutathione)

-SSRIs + St. John's wort (serotonergic syndrome)
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