Chem 5

What is the purpose of therapeutic drug monitoring?

What is the purpose of therapeutic drug monitoring?

-Ensure drug dosage is in a range that produces maximal therapeutic benefits \n -Identify when the drug is outside the therapeutic range

Why is TDM mostly unnecessary?

For most drug therapies, safe and effective dosages have been established

What is the dose providing therapeutic benefits as statistically derived from observations in a healthy population?

Standard dosage

What fraction of the drug interacts with the site of action and cause a biologic response?

Free or unbound

What is the biochemical pathway responsible for a large portion of drug metabolism?

Hepatic Mixed-Function Oxidase (MFO) system

How are drugs eliminated?

-Hepatic metabolism \n -Renal filtration \n -Combination of the two

What are the terms for lowest and highest levels of drug concentration?

Lowest: trough \n Highest: peak

Approximately how many doses are required before a steady-state oscillation?

5-7

What is the term for patients benefitting from therapeutic and desired effects of drugs?

Responders

What is the term for patients not benefitting from therapeutic and desired effects of drugs?

Non-responders

What is the gene group family that affects drug metabolism and the family of enzymes within the MFO system?

Cytochrome P-450

List 4 cardioactive drugs.

-Digoxin

-Quinidine

-Procainamide

-Disopyramide

What is a cardiac glycoside used in the treatment of congestive heart failure?

Digoxin

What does digoxin inhibit?

Membrane Na-K-ATPase

What is a natural occurring drug used to treat various cardiac arrythmias?

Quinidine

What is a group of chemically related antibiotics used to treat gram negative bacterial infections that are resistant to other less toxic antibiotics?

Aminoglycosides

What are the most common aminoglycosides?

Amikacin, gentamicin, tobramycin, kanamycin

What are the most serious effects of aminoglycosides?

Ototoxic & nephrotoxic

What is a bactericidal antibiotic effective against both aerobic and anaerobic gram positive rods and gram positive cocci? Effectively treats MRSA.

Teicoplanin

What is a glycopeptide antibiotic effective against gram positive cocci and bacilli infections?

Vancomycin

List 6 antibiotics.

-Gentamicin \n -Tobramycin \n -Amikacin \n -Kanamycin \n -Teicoplanin \n -Vancomycin

What are some side effects of vancomycin?

Red man syndrome, nephrotoxicity, ototoxicity

List 16 antiepileptic drugs.

-Phenobarbital

-Primidone

-Phenytoin

-Fosphenytoin

-Valproic acid

-Carbamazepine

-Valproate

-Ethosuximide

-Felbamate

-Gabapentin

-Lamotrigine

-Levetracetam

-Oxycarbazepine

-Tiagabine

-Topriamate

-Zonisamide

What two antiepileptic drugs are slow-acting barbiturate's that effectively control severe seizures?

Phenobarbital & Primidone

What is the inactive form of phenobarbital?

Primidone

What drug is most commonly used to treat seizure disorders?

Phenytoin

What drug is used as monotherapy for treatment of petit mal and absence seizures?

Valproic acid

List 4 psychoactive drugs.

-Lithium \n -Tricyclic antidepressants \n -Clozapine \n -Olanzapine

What psychoactive drug is used to treat manic depression?

Lithium

What class of drugs is used to treat depression, insomnia, extreme apathy, and loss of libido?

Tricyclic antidepressants

What is an atypical antipsychotic used to treat otherwise treatment-refractory schizophrenia?

Clozapine

List 4 immunosuppressive drugs.

-Cyclosporine \n -Tacrolimus \n -Sirolimus \n -Mycophenolic acid

What drug's primary clinical use is the suppression of host-versus-graft rejection of heterotopic transplanted organs?

Cyclosporine

What drug is 100x more potent than cyclosporine?

Tacrolimus

What is an antifungal agent with immunosuppressive activity and FDA approved for patients receiving kidney transplants?

Sirolimus

What drug is a lymphocyte proliferation inhibitor and most commonly used as supplemental therapy with cyclosporine and tacrolimus in renal transplant patients?

Mycophenolic acid

What bronchodilator is used in the treatment of respiratory disorders, such as asthma and stable chronic obstructive pulmonary disease?

Theophylline

List 1 antineoplastic drug.

Methotrexate

List 1 bronchodilator.

Theophylline

What is the study of adverse effects of xenobiotics in biological organisms?

Toxicology

What are the 3 major disciplines within toxicology?

-Mechanistic: cellular & biochemical effects of toxins; dose-response relationship \n -Descriptive: uses results of animal experiments to predict what level of exposure will cause harm in humans; risk assessment \n -Regulatory: uses data from mechanistic & descriptive to establish standards regarding acceptable levels of exposure; oversees human safety issues associated with therapeutic drugs, cosmetics, food additives

What are exogenous agents that may have adverse effects on a living organism; often used to describe environmental chemicals or drug exposures?

Xenobiotics

What have an adverse effect on biological systems; terminology used when describing animal, plant, mineral, or gas?

Poison

What are substances that are biologically synthesized in living cells or microorganisms?

Toxins

What are 4 examples of poisoning?

-Suicide attempt \n -Accidental exposure \n -Homicide \n -Occupational exposure

What are the most common routes of exposure to toxins, poisons, or xenobiotics?

Ingestion, inhalation, or transdermal absorption

What factors affect oral drug absorption?

-pH \n -Rate of dissolution \n -Gastric motility \n -Resistance to degradation in GI tract

The body's response to a drug is dependent mostly upon?

Dosage

What is a single, short-term exposure to a substance?

Acute toxicity

What is a repeated, frequent exposure for extended periods?

Chronic toxicity

What are some general toxic effects?

Disorientation, confusion, euphoria, unconsciousness, paralysis, death

What are some toxic effects from ethanol?

Diminution of judgment & motor performance

What is the established statutory limit of blood alcohol concentration when operating a vehicle?

80 mg/dL or 0.08%

What is a common solvent ingested accidentally as a component of many commercial products or as a contaminant of homemade liquors?

Methanol

What can ingestion of methanol cause?

Severe acidosis, death, blindness

What can cause severe acute-phase ethanol-like symptoms?

Isopropanol

What is a common component of hydraulic fluid and antifreeze?

Ethylene glycol

What is an important specimen requirement for measuring alcohols?

Specimen needs to be capped to avoid evaporation

What enzyme do we NOT measure metabolizes alcohol?

ADH

What is a colorless, odorless, tasteless gas that rapidly absorbs into blood from inspired air?

Carbon monoxide

What is found in industrial processes, insecticides, rodenticides; produced by burning of some plastics; common suicide agent?

Cyanide

What exists in both naturally occurring and manmade substances; exposure occurs in various settings, groundwater being the primary source?

Arsenic

What's main use is being in electroplating and galvanizing though it is also commonly encountered during the mining and processing of other metals?

Cadmium

What was a common constituent of household paints before 1972 and is still found in commercial paints and art supplies?

Lead

How is lead analyzed?

AAS & ICP-MS

Consumption of contaminated foods is the major source of exposure to what in the general population?

Mercury

Which metal is important for healing and immune function?

Zinc

Which 2 enzymes are measured due to pesticide exposure?

Acetylcholinesterase & butyrlcholinesterase

What is a commonly used analgesic drug and is associated with severe hepatotoxicity?

Acetaminophen

How is acetaminophen quantified?

Immunoassay or HPLC (reference)

What are the toxic effects of cocaine?

Hypertension, arrhythmia, seizure, myocardial infarction

How is cocaine analyzed?

Immunoassay and GC w/MS (confirmation)

List the drugs of abuse.

-Methamphetamines \n -Opioids \n -Fentanyl \n -Cannabinoids \n -Cocaine \n -Phencyclidine (PCP) \n -Barbiturates \n -Benzodiazepines \n -Anabolic steroids

Which addictive drugs can be used for weight loss?

Amphetamines

What are the toxic effects of anabolic steroids?

Males: testicular atrophy, sterility, impotence \n Females: masculine traits, breast reduction, sterility

Cholesterol is the base substance for synthesizing which type of drugs?

Anabolic steroids

All toxicology measurements in a laboratory must have what?

Screen & confirmatory test

State the steps of cancer staging and progression.

Stage 1: Localized primary tumor \n Stage 2: Invasion of primary tumor through epithelium and into blood vessels \n Stage 3: Migration of tumor into regional lymph nodes \n Stage 4: Metastasis and invasion of tumor to distant tissues

What is the 2nd leading cause of death in developed countries?

Cancer

What makes an ideal tumor marker?

Tumor specific, absent in healthy individuals, and readily detectable in body fluids

List the types of tumor markers.

-Enzymes \n -Serum proteins \n -Receptors \n -Oncofetal antigens

CK-BB can be used as a tumor marker for?

Prostate & breast

Tumor markers are not normally used to screen populations, what is the tumor marker that is the exception to this rule?

PSA

When does annual screening for PSA for men begin?

50 years old or younger if at high risk

What is the normal range for PSA?

<4 ng/mL

What factors contribute to interpreting tumor marker immunoassays?

-Linearity \n -Hook effect \n -Heterophile antibodies

What is determined by analyzing specimens spanning the reportable range?

Linearity

What is the span of analyte concentrations over which a linear relationship exists between the analyte and signal?

Linear range

What is when analyte concentrations exceed the analytical range excessively, there is potential for antigen excess?

Hook effect

What are circulating antibodies against animal immunoglobulins that can cause significant interference in immunoassays?

Heterophile antibodies

What is used to detect neuroblastoma, pheochromocytoma, and carcinoid tumors?

HPLC

What are serotonin-secreting tumors that arise from the small intestine, appendix, or rectum?

Carcinoid tumors

What tumor marker is often elevated in patients with hepatocellular carcinoma and germ cell tumors?

AFP

What tumor marker is useful in detecting ovarian tumors at an early stage?

CA-125

What is the most widely used tumor marker for colorectal cancer; also elevated in lung, breast, and GI tumors?

CEA

What tumor marker is used for diagnosis of testicular cancer, prognosis of ovarian cancer, and the most useful marker for gestational trophoblastic diseases?

HCG

List the ABCDE's in assessing nutrition.

A: anthropometric or body composition measurements

B: biochemical analyses

C: clinical examination

D: dietary analysis

E: environmental assessment

List 4 nutritional macronutrients.

-Thyroxine-binding prealbumin \n -Albumin \n -Transferrin \n -Nitrogen balance

What macronutrient has a long half life and is not a good indicator of short term malnutrition?

Albumin

What is an early indicator of iron deficiency or protein depletion?

Transferrin