TDM/TOX – Chemistry

Flashcard maker : John Smith

the study of how drugs interact with living organisms to produce a change in function and how the body affects the drugs.


if substances have medicinal properties, they are considered pharmaceuticals


the study of the body’s effects on the drug.


this includes the processes of absorption, distribution, metabolism, and excretion of drugs

pharmacodynamics (PD)
is the study of the physioogical effects of drugs on the body
therapeutic range
the range of serum drug concentrations associated with therapeutic effect (without toxicity) in the majority of patients

the lowest drug concentration during a dosing interval when drug is given intermittently.

the trough concetration generally occurs immediately before administration of the next dose.


the highest serum drug concetration that occurs following a single dose or at steady state within a dosing interval.


if the drug is given orally the peak is determined by the rate of absorption and the rate of elimination.


Exact peak concentration can’t be determined  w/o frequent serial blood sampling

half- life
the time required for serum drug concentration to decrease by 50%
Steady State
the equilibrium achieved during chronic dosing when the rate of the drug input equals the rate of the drug excretion
Minimum Effective Concentration (MEC)
 the minimum serum drug concentration neccesary to produce a desired therapeutic effect
Minimum Toxic Concentration (MTC)
the minimum serum drug concentration necessary to begin producing a toxic effect on the body
optimal dosing cycle

trough blood concentration should not fall below the  MEC and the peak blood concentration should not rise higher than the MTC


drug is administered once every half-life.


during dosing regimens should achieve steady state in which  concentration is greater than MEC but less than MTC


If the patient is greater than MTC they’re at risk for toxic effects


If the concentration is less than MEC patient’s at risk for the drug having no effect

for oral drugs must have greater than 70% level of the administered dose in order for it to be of therapeutic use.
First Pass& Liver Biotransformation

mouth> stomach>small intestine>liver


the liver is the principal organ responsible for drug metabolism


drugs are generally converted to polar, water-soluble molecules by atering chemical structure of the drug through oxidation, reduction, or hydrolysis reactions

Rate of absorption

you absorb medicine much faster than you excrete it


drugs that are admisinstered through iv must be formulated in much lower doses since 100% of it directly enters into the bloodstrem and avoids the first pass metabolic effect

conditions that influence the rate of drug absorption

abnormal GI motility


disease of infections of the GI tracts


food: vitamin K can reduce the effects of the drug coumadin (coumadin is less able to inhibit clotting factors)


co-administered drugs can affect gastric absorption by altering pH

drug interactions

synegistic: a drug that enhances the therapeutic effect of another drug; may be beneficial or harmful


antaognistic: a drug that diminishes the action of another drug; may be beneficial or harmful

drug distribution

drugs enter systemic circulation, it undergoes simultaneous distribution to body tissues and elmination by clearing organs (liver and kidneys)


lipophillic drugs can cross the cellular membrane

water-soluble drugs can interact with drug receptors on the cell to elicit a biological response.


acidic drugs generally bind to albumin while basic drugs generally bind to globulins

drug excretion

renal pathway is a major excretion route for water soluble drugs or drug metabolites


excretion of a drug from the body can also occur through intestinal and pulmonary routes

cardio active

a class of drugs used to treat heart conditions


some that requires TDM since they have a small therapeutic range

cardiac glycoside used in the treatment of carida arrhythmia
lidocaine quinidine and procainamide
used to correct ventricular arrhythemia and to prevent ventricular fibrillation

a class of drugs that is effective against a wide range of bacteria


both gram negative and gram positive

a group of chemically related antiobiotics used for the treatment of infection with gram-negative bacteria that are resistan to less toxic antibiotic

a glycopeptide antiobiotic that is effective against select gram positive bacteria.


because of poor absorption they are given through iv infusion

a class of drugs that is effective against epilepsy

a slow acting barbituate that effectively controls several types of seizures.


absorption is oral and slow


reaches peak 10 hrs after dose

phenytoin (dilantin)

used to treat a variety of seizure disorders


also used as a short term prophylactic agent in brain injury to prevent loss of function use


primarily administered orally

valproic acid (vpa)

used for treatment as an anticovulsant and mood- stabilization drug primarily in the treatment of epilepsy and bipolar disorder


also used to treat migrane headaches and schizophrenia

a class of drugs that is effective at affecting the mind or behavior

an orally administered drug used to treat manic- depressive illness ( bipolar disorder)


absorption is complete and rapid

trycyclic antidepressants
are a class of drugs used to treat depression, insomnia, and extreme apathy
a class of drugs that are effective at dialation or expanding the air passages of the lung
an aerosol adminstered drug used in the treatment of asthma and other chronic obstructive pulmonary diseases (COPD)
Detection of non- compliance

discontinuing medicine after a patient feels better


forgetting to take medication regularly or follow the prescribed dosage


can result in the heightening of the disorder, significant toxicity, and/or treatment failure

therapeutic drug monitioring

detects patients undergoing changes in drug dispostion charateristcs.


establishes a basleline for therapeutic concentration:


a baseline drug concewntetation a twhich the patient responds os established and implemented


should the patient’s response change the clinic can determine whether the patient has non- compliant or whether diesease state or other factors have altered the pharmocokentics

collection,handling , and storage of toxicological examination

legal request will require a chain of custody


proper specime and preservation is required. always follow the sop


properly label and seal the containers.


sign and date the appropriate chain of custody


must be in custody of appropriate personnel at all times or in a locked container to avoid any legal objections


analysis is run in duplicate alongside known controls


legal toxicology results are NEVER given over the phone

the science of poisons and their effect on the body
a chemical agent that when ingested injected inhaled or absorbed can cause tissue death or injury

the amount of chemical agent introduced to the body.


for many medications, the right dose differentiates poison from remedy

lethal dose 50 quantity
susbstance required to cause death in 50% of the sample group
therapeutic dose
the amount of substance that will produce a desiredc pharmacological
drug of abuse

any drug used i excess or for non-therapeutic reasons


these drugs have high abue potential and users can become addicted

drug addiction

a severe physiological degree of drug dependence with a continuing involvement in drug use



mechanisms of toxicity

interference with critical enzyme actions ( ex. nerve agents inhibiting acetylcholinesterase)


blockage of O2 usage and transport (ex. carbin monoxide poisining)


intereferes with cell function


hypersensitivity reactions


factors of toxicity


nature of toxicant

water soluble substances are less likely to penetrate the skin than lipid soluble substances

factor of toxicitiy:


route of exposure

how was the toxin absorbed ( ex. inhalation)

factor of toxicity:



the amount of chemical agent exposed to

factors of toxicity:


drug interactions/ biological variables

drug interactions: synergistic, antagonisitic


biological variables: these will vary according to the individuals age gender genetics and overall health factors

specializied areas of toxicology:


clinical toxicology

analysis of drugs, heavy metals and other chemical agents in tissues, blood or body fluids to support patient care



specialized areas of toxicology:


forensic toxicology

addresses the effects of potentially toxic substances on the living or as a determination of cause of death to aid medico-legal investigations

specialized areas of toxicology:


environmental Toxicology

analyzes the harmful effects of exposure to chhemicals present in the natural environment or industrial sources
cocaine, amphetamines, methamphetamine, and MDMA
marijuana, hashish
CNS depressants
barbituates, alcohol, and benzodiazepines
morphine, codeine, oxycodone, oxymorphine, heroin, opium
psychedelics (hallucinogens)
LSD, desiner amphetamines, peyote, psilocybin, phencyclidine
sports enhancing drugs
anabolic steroids, hGH
General stimulants
nicotine, tobacco, and caffeine
inhalants;and anesthetics
volatile nitrates, organic solvents
medico- legal aspects
cases in which the possiblity of criminal poisoning; exists or cases in which leagal action may be taken on order to determine liablilty
chain of custody
unbroken documentation trail of accountability that guarentees a samples physical security.
certain yeats and bacteria anaerobically metabolise sugar into ethanol

process by which solutions containing alcohol are heated and the vapors collected and condensed back into the liquid


means of concentrating ethanol

major uses of alcohol

alcoholic bevarages


solvents ( perfumes, varnish, mouthwash, antiseptic, cough medicine)


antedote for methanol poisoning

legal issues with alcohol
a BAC result of 0.08% is legal evidence for criminal conviction for intoxicated driving
metabolism of alcohol

rapidly absorbed from the GI tract


approximately 20% is absorbed in the stomach


80% absorbed in the small intestine


from 90-98%; is oxidized to acetaldehyde by the enzyme alcohol dehydrogenase

physiological affects of alcohol

muscular system- coordination is impaired


circulatory system- blood vessels dialate causing increased loss of body heat


respiratory system-small doses stimulate respiration


nervous system- lowered social inhibitition at low doses followed by mental confusion and uncontrolled mood swings at higher levels


digestive system- increase digestive secretions cause stomach irritation ( increased pH)


endocrine- secretions of various hormones may be altered

physiological effects of alcohol on


female reproduction

during pregnancy can cause lead to miscarriages, infant deaths, and smaller, weaker new borns

birth defects include Fetal Alcohol Syndrome


( in males leads to impotence and testerone levels)

detoxification of alcohol

clear the stomach


withdrawl may cause delirium tremens: a condition associated with tremors, tachycardia, hypertension diaphoresis, hallucinations, delusions, disorientation, and possibly seizures

After care of detoxification



nutritous diet supplemented with vitamins


behavior modification to teach avoidance and coping mechanisms


used as a common over the counter analgesic medication


water-solube glcuronide metabolized by the cytochrome p450 enzyme in the liver


poisoning caused if large amounts are taken


renal damage occurs less frequently but by the same mechanism

carbon monoxide

toxicity is a consequence of cellular hypoxia


most commonly encountered toxic gas


CO binds to hemoglobin with an affinity 250 times greater than O2


co may also directly inhibit extracellylar enzymes like cytochrome oxidase further disrupting cellular function

heavy metal

includes lead, mercury, and arsenic


lead is toxic to multiple organ systems


associated with;alterations in cellular and mitochondrial membranes diminshed neurotransmitter and heme synthesis and impeded nucleotide metabolism


frequently found in house paint and used to be an additive in gasoline

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