Exam 3 TDM/Toxicology Flashcards
Define therapeutic drug monitoring
the analysis, assessment, and evaluation of circulating concentrations of drugs in serum, plasma, or whole blood
Purpose of TDM
to ensure that a given drug dosage produces maximal therapeutic benefit and minimal toxic adverse effects
Advantages of TDM
o Identifying non-compliant patients
o Maximizing therapeutic effect
o Optimizing a dosing regimen based on drug-drug interactions
Factors that influence drug effect and dosage
Age, weight, tolerance, rate of elimination, time of administration, genetic factors, metabolism of other drugs, protein binding, disease states, medication errors/compliance
What does LADME stand for?
Liberation Absorption Distribution Metabolism Excretion
What is liberation?
The release of the drug from its dosage form
What is absorption?
Rate at which drug leaves site of administration and the extent to which this happens
What is distribution?
the process by which drug diffuses or is transferred from intravascular space to extravascular space (body tissues)
- blood flow, capillary permeability
What is metabolism/biotransformation?
o Transformation of the parent drug molecule into one or more metabolites by enzymes
What is MFO?
– hepatic mixed function oxidase
Converts hydrophobic substances into water-soluble substances
Then transported to bile or released into circulation for elimination
What is elimination/excretion?
o Rate of change of drug concentration over times varies continuously with the concentration
o Functional changes in organs can affect rate of elimination (such as hepatic disease/cirrhosis – slows clearance)
Routes of drug administration
- Injections – IV (fastest), intramuscular, subcutaneous, epidermal
- Inhalation
- Absorbed through skin (slowest)
- Rectal
- Oral
What is cytochrome P450?
- Major enzymes that metabolize drugs
* Gene group family that affects drug metabolism
What is pharmacogenomics?
the study of how a person’s unique genetic makeup (genome) influences his or her response to medications.
What is first-pass metabolism?
- Drugs administered through IV enter directly into systemic circulation
- Drugs administered orally are first exposed to the liver and may be metabolized before reaching the rest of the body
What are some routes of elimination?
- Hepatic metabolism
- Renal filtration
- Skin, lungs, mammary glands, salivary glands
What are examples of cardioactive drugs?
Digoxin, lidocaine, quinine, procainamide
What is digoxin?
- Used to treat CHF
- Draw peak levels 2 hours post dose
- Allows for better cardiac muscle contraction and rhythm
What is lidocaine used for?
Used to treat premature ventricular contractions
What is quinidine used for?
- Used to treat cardiac arrhythmias
* Prevents arrhythmias, atrial flutter, fibrillation
What is procainamide used for? How is it measured?
- Used to treat cardiac arrhythmic situations
- Affects cardiac muscle contraction
- Often measured with NAPA (N-Acetyl procainamide)
Different types of antibiotics
Aminoglycosides, vancomycin
What are aminoglycosides used for?
- Gentamicin, tobramycin, amikacin, kanamycin
• Used to treat infections with gram-negative bacteria
• Inhibits protein synthesis of the microorganism
Side effects of aminoglycodies
nephrotoxic, ototoxic
What is vancomycin used for?
- Used to treat infections with more-resistant gram-positive bacteria
- Inhibits cell wall synthesis
First generation anti epileptic drugs
phenobarbital, phenytoin (Dilantin), valproic acid (Depakane), carbamazepine (Tegretol)
Second generation. anti epileptic drugs
felbamate, gabapentin, oxcarbazepine, topiramate, etc.
Examples of psychotherapeutic drugs
- used to treat manic depression/BD
• Lithium
• Tricyclic antidepressants
• Clozapine – schizophrenia
Antiasthmatic drugs
o Theophylline and theobromine
What are immunosuppressive drugs used for?
o Monitoring of this group is important to prevent organ rejection
o Used to treat autoimmune disease
Examples of immunosuppressive drugs
o Cyclosporine – whole blood
o Tacrolimus – prevents rejection of liver and kidney transplants
What are antineoplastic drugs? Example?
o Inhibits RNA or DNA synthesis of tumor cells, leading to cell death
o Methotrexate – inhibits DNA synthesis of all cells
What are protease inhibitors?
o Antiviral drugs used to treat HIV/AIDS, hepatitis C
o Inhibit viral replication
• Indinavir, ritonavir, lopinavir, nelfinavir
Define half-life
time needed for the serum drug concentration to decrease by one-half
Define steady state
time at which the rate of elimination = the rate of administration
Methodology used for TDM
- Immunoassays
* Chromatography and mass spectrometry
Biomagnification vs bioaccumulation
• Biomagnification – across a food chain, toxin concentration can build up over time if it is fat soluble
o DDT, organic forms of mercury/arsenic
• Bioaccumulation – chronic poisoning from the environment or workplace
o Mad hatter syndrome – mercury
Describe ethanol toxicity
- Chronic exposure leads to alcohol hepatitis/cirrhosis
- Increased GGT, AST, HDL
- Deritis ratio >2.0
Describe methanol toxicity. How does it affect AG and osmolality?
- Found in homemade liquor & commercial products
- Increased AG and serum osmolality
- Serum osmo increases by about 10mOsm/kg for each 60mg/dL increase in serum ethanol
Describe ethylene glycol toxicity
- Causes metabolic acidosis & renal damage
- Calcium oxalate crystals (envelopes)
- Sweet taste attracts children/pets
Legal levels for alcohol
• Legal 80-100 mg/dL (0.08 – 0.10%)
Lethal level for alcohol
> 400 mg/dL
Characteristics of carbon monoxide
o Colorless, odorless, tasteless
o Rapidly absorbed into blood
o Produced by incomplete combustion of carbon-containing substances
Actions of CO
o Binds tightly to HGB and does not allow O2 to attach, forming carboxyhemoglobin
o Decreases O2 delivery to tissues = hypoxia
Characteristics of cyanide toxicity. Where is it found?
• Found in industrial processes, insecticides, burning plastics
• Toxic by binding to heme iron
o Pesticides – decreased in cholinesterase levels are indicative of exposure to insecticides
Symptoms of cyanide toxicity
• Causes headaches, dizziness, respiratory depression, leads to seizure/coma/death
Where are organophosphates found?
insecticides/pesticides
Describe aspirin toxicity
o Overdose causes severe hepatotoxicity
o Damage not apparent until 3-5 days after ingestion
Function of salicylates
o Fever reducer/pain reliever
o Decreases thromboxane and prostaglandin formation
Inhibition of cyclooxygenase which interferes with platelet aggression
Toxicity of salicylate
o Metabolic acidosis
Formation of ketones due to fatty acid metabolism
Hyperventilation
Identify parameter of alteration testing
- Temperature <91ºF or >100ºF
- Ph <4.5 or >11
- Specific gravity <1.003
- Creatinine <20mg/dL
- Presence of bleach, glutaraldehyde, nitrite
What are amphetamines?
o Stimulant used to treat narcolepsy and ADD
o Ephedrine, pseudoephedrine, “ecstasy”/MDMA
OD symptoms for amphetamines
hypertension, convulsions, cardiac arrhythmia
Chronic use of steroids causes:
Toxic hepatitis
Atherosclerosis
Abnormal platelet aggregation
Heart enlargement
Half-life for cannabinoids
1 day after single use, 3-5 days after chronic use
Function of cocaine
CNS stimulator & local anesthetic
Primary metabolite of cocaine
Benzolecgonine
OD symptoms of cocaine
Hypertension, arrhythmia, seizure, MI
o Detect in urine for 3 days post single use, 20 days chronic use
Function of opiates
Sedative, provides pain relief
Types of opiates
opium, heroin, morphine, codeine, Dilaudid, Percodan, Demerol, Oxycontin
OD symptoms of opiates
Respiratory acidosis
Myoglobinuria
Cardiac damage
Death by cardiopulmonary failure
Example of PCP
o Ketamine – veterinary analgesic, anesthetic
o Street names
Vitamin K, special K, super K
Types of sedatives
o Barbiturates – phenobarbital, secobarbital
o Benzodiazepines – less toxic than barbiturates
Valium, Ativan
Rohypnol – sexual assault drug
Not detected in drug screens
OD symptoms of sedatives
Slurred speech, lethargy, coma
Function of bath salts
“Vanilla sky”
o Produce stimulant/hallucinogenic effects
Euphoria, increased sex drive
OD symptoms for bath salts
o Can result in life-threatening effects
Anxiety, paranoia, tachycardia, chest pain, hostile behaviors
Difficult to screen for in ED, recipe keeps changing
What is Krokodil?
Synthetic form of desomorphine
Similar to heroin highs
Named for effect it has on skin
What is salvia?
“Magic mint”
Produces hallucinogenic effects
What are synthetic cannabinoids?
“Spice” or K2
Produces euphoria
Difficult to detect
