CLINICAL CHEMISTRY
Toxicology
 Toxicology
- study of the adverse effects of chemicals (xenobiotics)
on living organisms.
 Xenobiotics
- chemicals and drugs not normally found or produced in
the body.
- Foreign substances in the body (synthetic chemical agent)
 Toxicologist
- person dealing with those adverse effects/side effects
- responsible for studying the adverse/side effect of
chemical agents
DIFFERENT AREAS OF TOXICOLOGY
1. Mechanistic Toxicology
- dose–response relationship
- concerned with the identification in understanding the
biochemical, cellular, and molecular mechanism by
which chemical exert toxic effect in living organism
2. Descriptive Toxicology
- toxicity testing for risk assessment
- uses result from animal experiment to predict what level
of exposure can cause harm to human
- responsible for providing information for safety
evaluation and regulatory requirements
3. Regulatory toxicology:
- establish standards that define the level of exposure for
public health or safety.
- Responsible in deciding whether a drug or chemical
reagent has sufficient low risk to be marketed
- Responsible for the interpretation of the combined data
from mechanistic and descriptive studies
ORGANIZATIONS
 FDA (BFAD)
- is responsible for allowing drugs, cosmetics, and food
additives to be sold in the market.
- Also responsible for giving the certificate of product
registration/CPR (test kits, reagents, etc.)
 U.S. Environmental Protection Agency (EPA)
- is responsible for regulating other chemicals according to
the Federal Insecticide, Fungicide and Rodenticide Act.
 Occupational Safety and Health Administration (OSHA)
- is responsible for ensuring safe and healthy work
environments.
- Occupational Safety and Health Center (OSHC) – in the
Philippines
 Consumer Product Safety Commission
- regulates household chemicals. (dishwashing liquid,
bleach, insecticides)
 Department of Transportation
- oversees transporting of chemical hazards.
- Bureau of Customs – in the Philippines
OTHER SPECIALIZED AREAS OF TOXICOLOGY
1. Forensic toxicology
- medico legal aspects of the harmful effects of chemicals
- concerned in establishing the cause of death
- in determination death circumstances in post mortem
investigation
pg. 1
- identify what is present in the body
2. Clinical toxicology:
- study of interrelationships between xenobiotics and
disease states and therapeutic intervention.
- Deals with diseases caused by or associated with toxic
substances
- Establish the cause and effect or the toxic kinetic of
poisoning (adverse effect of toxin)
- Also determine how to diagnose and prescribe treatment
of poisoning
3. Environmental toxicology:
- hazards of chemical pollutants in the environment
4. Ecotoxicology:
- impacts of toxic substances on population dynamics in an
ecosystem
TERMS AND DEFINITIONS
 Poison
- any substance that causes a harmful effect to a living
organism
- relative compound in small quantity can cause death or
disability
 Toxicant:
- is any chemical, of natural or synthetic origin, capable of
causing a harmful effect to a living organism.
 Toxin:
- is a toxicant produced by a living organism and is not
used as a synonym for toxicant, all toxins are toxicants,
but not all toxicants are toxins.
 Antidote
- medicine given to counteract the influence of poison or
an attack of disease.
- First aid for poisoning (anti-rabies vaccine)
HISTORY
 Paracelsus
“All substances are poisons. There is none which is not a poison.
The right dose differentiates a poison & a remedy.”
 Mathieu Orfila (1831)
- the modern father of toxicology.
MEASUREMENT OF TOXICANTS AND TOXICITY
 Deals with analytical chemistry, bioassay, applied mathematics.
 Designed to provide the methodology to answer the following:
- Is the substance likely to be toxic?
- How can we assay its toxic effect?
- What is the minimum level at which this toxic effect can
be detected?
- Measurement of Toxicants and Toxicity
Routes of Exposure
 Toxins can enter the body via several routes:
- Ingestion
- Inhalation
- transdermal absorption being the most common ones.
ABSORPTION OF TOXINS
1. Systemic effect -absorbed into circulation. (intravenous or
intramuscular)
 CLINICAL CHEMISTRY

2. Gastrointestinal tract -Passive diffusion – process requires the - response relationship-pertains to changing health effects
hydrophobic substances that have the ability to diffuse across based on the change in xenobiotic exposure levels.
cell membrane and substances cross the cellular barrier.  Quantal dose
 Other factors can influence absorbance of toxins from the - response relationships -describe the change in health
gastrointestinal tract effects of a defined population based on changes in the
- the rate of dissolution (the higher that It dissolve, the exposure to xenobiotics.
faster it will absorb)
- gastrointestinal motility DURATION OF EXPOSURE
- resistance to degradation in the gastrointestinal tract 1. Acute toxicity
(malabsorption) - a single, short-term exposure to a substance
- interaction with other substances. - the dose of which is sufficient to cause immediate toxic
 Ionized substances may not pass through the cell membrane effects.
because weak acid may be protonated by gastric acid, therefore 2. Chronic toxicity
it will not be absorb. - repeated frequent exposure for extended periods for
 Toxins that are not absorbed from the gastrointestinal tract do greater than 3 months and possibly years, at doses that
not produce systemic effects (fever) but may produce local are insufficient to cause an immediate acute response.
effects, such as: TOXICITY SCREENING
- Diarrhea  mutagenicity
- Bleeding - detection of possible ability to induce genetic alteration
- malabsorption of nutrients (mutation)
 carcinogenicity
DOSE-RESPONSE RELATIONSHIP - detection of possible ability to induce abnormal clonal
 evaluate several responses over a wide range of concentrations uncontrolled proliferation of genetically altered cells
 may apply to an individual or a population.  teratogenicity
TOXICITY RATING SYSTEM - detection of possible deleterious effects on the
Toxicity Rating Lethal Oral Dose in Average developing fetus
Adult
Super toxic <5 mg/kg SIGNAL WORDS
Extremely toxic 5-50 mg/kg The relative acute toxicity of a chemical is reflected on the label in
Very toxic 50-500 mg/kg the form of a “signal word”.
Moderately toxic 0.5-5 g/kg  CAUTION -lowest degree
Slightly toxic 5-15 g/kg  WARNING -intermediate degree
Practically nontoxic >15 g/kg  DANGER -highest degree

MEASURES OF TOXICITY TOXICOLOGY OF SPECIFIC AGENTS

1. TD50 – toxic dose  Alcohol
2. LD50 – lethal dose  Carbon Monoxide
3. ED50 – effective dose  Caustic Agents
 Therapeutic index – is the ratio of the TD50 (or LD50) to the  Cyanide Metals
ED50  Metalloids Pesticides
TOXICOLOGY OF THERAPEUTIC DRUGS
 salicylates
 acetaminophen
TOXICOLOGY OF DRUGS OF ABUSE
 amphetamines
 anabolic steroids
 cannabinoids
 cocaine
 opiates
 phencyclidine
 sedatives–hypnotic

 Individual dose
Essential Laboratory Test
pg. 2
 CLINICAL CHEMISTRY

I. CLINICAL TEST  Clinical Pearl/Significance: Anion gap acidosis with an osmolar

A. SERUM ELECTROLYTES gap should suggest methanol or ethylene glycol poisoning
 Hyponatremia due to
- Lithium E. URINE ANALYSIS
- Amitriptyline (TCA)  for (myoglobinuria in toxic hyperthermia, opioid abuse
 Hypokalemia due to withdrawal crystalluria as calcium oxalate in fluoride
- Theophylline – use for respiratory distress (asthma) poisoning).
- B2 agonist – relaxation of smooth muscle  ALSO, Urine drug screen (beware of cross reactivity, i.e.
Diphenhydramine, methadone, can make PCP screen +)
B. OTHER LABORATORY MEASUREMENT THAT HELP IN
DIAGNOSIS OF POISONING F. ALCOHOL SCREENING
 Glucose level  Breath Ethanol Test
- Hypoglycemia: glucose, insulin, caffeine, theophylline  Urine Screening Test
- Hyperglycemia: propanol (calcium channel blockers),  Analysis of Serum/Plasma and Blood Ethanol
salicylates (anti-pyretics)
 BUN and Creatinine: to evaluate renal function
 Ethylene glycol, heavy metals, PCP, amphetamine, cocaine –
can cause renal dysfunction/problem
 LFTs (ALT, AST), CK
- LFTs – Tylenol, arsenic, ethanol, iron, valproic acid
- CK – rigidity, arrhythmias, PCP, cocaine

C. ANION GAP MCV – act as inhibitor; inhibit enzyme D-ALA synthetase and B12
 The anion gap provides an estimation of the unmeasured deficiency
anions in the plasma and is useful in the setting of arterial blood G. TOXICITY SCREEN (serum level)
gas analysis.  Specific drug levels that can be detected:
 It is especially useful in helping to differentiate the cause of a Not more than 140 mg/L
metabolic acidosis, as well as following the response to therapy. Acetaminophen after 4 hour of ingestion.
 Anion Gap = (Na++ K +) -(Cl-+ HCO3-)
 The normal value for the anion gap is 10 +/-2 m eq. /L. Amitriptyline 120 to 150 ng/mL
 Anion gap gives you clues to the ingested substance and helps Carbamazepine 5 to 12 mcg/mL
you prevent dangerous complications Digoxin 0.8 to 1.2 ng/mL
 Typical causes of an elevated anion gap metabolic acidosis due Disopyramide 2 to 5 mcg/mL
to poisoning (MUDPILES)
Imipramine 150 to 300 ng/mL
- Methanol
Lidocaine 1.5 to 5.0 mcg/mL
- Uremia induced by poisoning
Lithium 0.8 to 1.2 mEq/L
- Diabetic ketoacidosis
Phenobarbital 10 to 30 mcg/mL
- Paraldehyde, phenformin
Phenytoin 10 to 20 mcg/mL
- Iron, Isoniazid, Inhalants (i.e. carbon monoxide, cyanide,
Procainamide 4 to 10 mcg/mL
toluene),Ibuprofen.
Propranolol 50 to 100 ng/mL
- Lactic acidosis induced by poisoning
Quinidine 2 to 5 mcg/mL
- Ethylene glycol, Ethanol (alcoholic ketoacidosis).
- Salicylates, Solvents, Starvation. Salicylate 00 to 250 mcg/mL
 Typical causes of a low anion gap Theophylline 10 to 20 mcg/mL
- Hypoalbuminemia Valproic acid 50 to 100 mcg/ml
- Hypocalcaemia H. DRUG SCREEN
- Hyperkalemia  For detection of drugs of abuse
- Hypermagnesemia I. Electrocardiogram
- Lithium toxicity  Prolonged QRS: As in poisoning with TCAs, Phenothiazines,
- Multiple myeloma – malignancy in the lymphatic CCB, etc.
tissues/immunoglobulin in the bone marrow  Sinus bradycardia/AV block: As in poisoning with TCAs, BB ,
D. OSMOLAR GAP Calcium channel blockers, Digoxin, Organophosphates, etc.
 Calculated osmolality – measured osmolality = 2[Na+] +  Ventricular tachycardia: As in poisoning with Cocaine,
glucose/18 + BUN/2.8 amphetamines, TCAs, Digoxin, Theophylline, CCB, etc.
 Normal = 285-290 mOsm/L II. TOXICOLOGICAL SCREENING (Analytical Methods)
A. QUALITATIVE METHOD
 Gap > 10 mOsm/L suggests the presence of extra solutes:
1. Chemical Spot Tests
- Ethanol, methanol
- A test for a substance using reagents that together
- Ethylene glycol, isopropyl alcohol
generate an easily observed color or some other
- Mannitol, glycerol
physical change in the presence of the target
substance.
pg. 3
 CLINICAL CHEMISTRY
- Spot tests for blood, semen or certain drugs can be
done at a crime scene, but often the positive
results are indicative only, and need more
sophisticated testing for court evidence.
- Direct (color tests) in serum or urine sample:
a. Carboxyhemoglobin in whole blood
- Dilute a sample of the blood 1 in 20 with
0.01M ammonia and compare the color
with a sample of normal blood treated
similarly. A pinkish tint suggests the
presence of carboxyhaemoglobin
(COHb).
- Modern clinical gas analyzers
automatically measure the COHb, and
therefore this color test is required
rarely.
b. Salicylates
- Trinder’s reagent (40 mg of mercuric
chloride in 850 mL of water add 120 mL
of 1 M hydrochloric acid and 40 g of
hydrated ferric nitrate and dilute to
1000 mL with water) is used.
c. Direct (color tests) in serum or urine sample
- Blood glucose: Hypoglycemia is a
feature of overdose with insulin,
ethanol, ASA , etc.
- It can also occur in the early stages of
liver damage after severe poisoning with
paracetamol.
- Ketones in urine: Dip a „Labstix‟ strip
briefly into the urine and read after 10
to 15 s. A positive result for ketones may
indicate intoxication by acetone or
isopropyl alcohol. This test may also be
positive in starvation or in diabetic
ketosis.
d. Organophosphorus compounds
- cholinesterase inhibitors test in serum.
e. Phenothiazines
- ferric (III) chloride–perchloric acid–nitric acid (FPN)
reagent in urine.
2. Immunoassay test
- Kit for drugs of abuse Immunoassay
- These assays are relatively specific for a single drug
(LSD), but in others, several drugs of a similar class
are detected(e.g., opiates).
- The detection limit for various members of a class
of drugs or the degree of cross-reactivity for similar
drugs varies, and each manufacturer of
immunoassay reagents should be consulted for
specific information.
- These assays are easy to perform; many are
available for use on automated instrumentation and
may be able to provide “semiquantitative” results.
- For the vast majority of drugs of abuse,
immunoassays are the methods of choice for initial
screening.
3. Thin layer chromatography (TLC)
- Urine samples or, if not available, stomach contents
that have been purified prior to extraction.
pg. 4
- Any particulate material in the stomach contents
should be removed by filtration or centrifugation
prior to solvent extraction.
- Urine is the specimen of choice because most drugs
and drug metabolites are present in urine in
relatively high concentrations.
- Many TLC systems have been developed for use in
hospital toxicology. These include the commercial
Toxilab system which provides standards for the
substances and metabolites most commonly
encountered in intoxicated patients.
- The most generally used mobile phase is
chloroform: methanol (9:1 v/v), although some
countries now require the less toxic
dichloromethane to chloroform.
- In hospital toxicology it is advisable to use at least
two separate mobile–phase systems to obtain a
more definitive result. 20 cm ×20 cm silica–gel
plates with or without fluorescent indicator is the
most popular, although smaller sizes can also be
used.
4. Spectrophotometric Methods
B. QUANTITATIVE METHOD
1) GC-MS -Mass Spectrometry (GOLD STANDARD)
2) Infrared
3) HPLC
4) GCS
C. Others
Confirmation/Quantitation
Validated Method with Detailed SOP: (Accepted Standard
Operating Procedures)
- Extraction Procedures
- Chromatography Procedures
- Gas and Liquid Chromatography
- Mass Chromatography
a. Gas chromatographic screening for drugs
- Gas–liquid chromatography (GLC) with capillary
columns and a nitrogen–phosphorus detector
(NPD), or with an electron capture detector (ECD) in
series, is a powerful screening system that is
sensitive enough to detect many of the compounds
of interest in small samples of serum, plasma or
whole blood, as well as in urine specimens.
b. Gas–liquid chromatography screening for alcohols and
other volatile substances
- In normal practice it is advisable to measure the
more volatile alcohols (methanol, ethanol, acetone
and isopropyl alcohol) separately from the higher
alcohols, trichloroethanol and the metabolites of
gamma hydroxybutyric acid (GHB), but for screening
it is possible to detect all at two different
temperature steps.
c. HPLC screening using the systematic toxicological
identification procedure
- The systematic toxicological identification
procedure (STIP) system (system HZ) is based on a
rapid and simple extraction method followed by
isocratic reversed phase HPLC with diode–array
detection.
- A library of retention times and UV spectra is
available for about 400 common drugs.
 CLINICAL CHEMISTRY

- A disadvantage of the system is that a large

number of drugs elute between 1 and 3 min and
this problem is exacerbated with substances
devoid of a characteristic UV spectrum (e.g.
maximum <210 nm).
- In such cases a second chromatographic analysis
may be required. The technique is also less
sensitive than GC screening methods.
5. Immunochemical Method
a. Fluorescent polarization immunoassay
- Is a type of homogeneous fluoroimmunoassay
that is widely used to measure drugs and other
small molecules.
- The polarization of the fluorescence from a
fluorescein-antigen conjugate is determined by
its rate of rotation during the lifetime of the
excited state in solution.
- A small, rapidly rotating fluorescein antigen
conjugate has a low degree of polarization;
however, binding to a large antibody molecule
slows down the rate of rotation and increases
the degree of polarization. Thus binding to
antibody modulates polarization, and a
homogeneous assay is possible.

b. Enzyme multiplied immunoassay technique (EMIT)

- Is a homogeneous EIA that is very widely used in
clinical analyses, Because EMIT does not require
a separation step, it is simple to perform and
has been used to develop a wide variety of drug,
hormone, and metabolite assays.
- In this technique, antibody against the analyte
drug, hormone, or metabolite is added together
with substrate to the patient’s sample.
- Binding of the antibody occurs. An aliquot of the
enzyme conjugate of the analyte is then added
as a second reagent; the enzyme hapten
(analyte) conjugate binds with the excess
analyte antibody, forming an antigen-antibody
complex.
- This binding of the analyte antibody with the
enzyme analyte conjugate affects enzyme
activity by physically blocking access of the
substrate to the active site of the enzyme, or by
changing the conformation of the enzyme
molecule and thus altering its activity.
- To complete the assay, the resultant enzyme
activity is measured. The relative change in
enzyme activity resulting from the formation of
the antigen-antibody complex is proportional to
the hapten concentration in the patient’s
sample. Concentration of the analyte is
calculated from a calibration curve prepared by
analyzing calibrators that contain known Therapeutic Drug Monitoring (TDM)
quantities of the analyte in question.
 Therapeutic drug monitoring (TDM)

pg. 5
 CLINICAL CHEMISTRY

- Involves the coordinated effort of several health
professionals to measure and monitor circulating drug
levels primarily in serum, plasma, or whole blood.
- Measures concentration of the drug in the blood at time
interval
- Study drugs that have narrow therapeutic window, high
patient variability in pharmacokinetics, have potential for
severe adverse effect, etc.
GOAL
 Ensure that a given drug dosage produces:
- Maximal therapeutic benefit
- Minimal toxic adverse effects
 Must have an appropriate concentration at site of action that
produces benefits
 Relationship of drug concentration to time
 Process assists in establishing or modifying a dosage regimen
A. ABSORPTION
 Rate at which drug leaves the site of administration and the
extent to which this happens
 Process by which drug molecules gain access to the blood
stream from the site of administration
 It can pass through cellular walls
 Drugs need to be lipid soluble (suitable for absorption and
distribution) to penetrate membrane, unless there is an active
transport system
 Mechanism
- Passive diffusion – along concentration gradient
- Active diffusion – against the concentration gradient

Therapeutic window – concentration of drug in plasma, whereas the

drug has therapeutic effect without causing toxic effect.
ROUTES OF ADMINISTRATION
 Injections (parenteral)
- Circulation – IV (intravenous) I. Limiting factors
- Muscles – IM (intramuscular) Oral Administration
- Skin – SC (subcutaneous)  Absorption depends on:
- Epidermal - Formation of drug (liquid/pill)
 Inhaled - Intestinal motility
 Absorbed through skin - pH
 Rectal - Inflammation – associated with down regulation,
expression, and activity of the cytochrome P450 enzymes
 Oral (most common)
involved in hepatic drug metabolism
- Food
- Presence of other drugs (drug interaction: synergism and
antagonism)
- Patient age - decline
- Pregnancy
- Concurrent pathologic conditions (e.g. gastroenteritis,
gastric ulcer, pyloric stenosis – require gastric emptying
rate)
 Bioavailability – measure of the rate and extent to
which the drug reaches the systemic circulation;
varies depend on drug formulation (IV bolus –
100%)
PHARMACOKINETICS B. DISTRIBUTION
 Involves the dynamics associated with the movement of drugs Dependent on:
across cell membranes  Blood flow
 Includes biological events:  Capillary permeability
- Absorption - pH gradients
- Distribution - Lipid solubility of the drugs
- Metabolism/Biotransformation  Binding of drugs to proteins/Availability of free fractions
- Excretion / Elimination - Free vs bound drug

pg. 6
 CLINICAL CHEMISTRY

 Tissue volume  Elimination half-life

C. METABOLISM
 Primarily occurs in the liver
 Process by which drug are chemically changed from a lipid
soluble form to a more water soluble form
 Biotransformation of the parent drug molecule into one or
more metabolites
 Metabolites are:
- Water soluble (suitable for excretion)
- Easily excreted by kidney or liver
- Pharmacologically active or inactive
I. First-Pass Metabolism
- A phenomenon of drug metabolism whereby the
concentration of a drug, specifically when administered
orally, is greatly reduced before it reaches the systemic
circulation.
- Aka first-pass effect/pre-systemic metabolism
- Use different route to avoid first-pass effect/pre-systemic
metabolism (IV, IM, suppository, inhalational,
transdermal, sublingual)
- The time required to reduce the blood level concentration
to one-half after equilibrium is obtained
- 100mg dose of an IV drug with t1/2 of 15 mins.
- How many mg of the drug will remain in the body after 15
mins? 50mg
PHARMACOKINETICS
Most drugs given on a scheduled basis not as a single bolus or mass
 Oscillation between a maximum (peak) and a minimum (trough)
of serum concentration
 Goal of dosage regimens
- Achieve troughs in therapeutic range and peaks that are
non-toxic
SAMPLE COLLECTION
I. Timing of TDM most important
 Collaborate with nursing and phlebotomy staff for
appropriate timing
- Trough : right before next dose (0-60 mins)
- Peak : one to two hour post administration of dose
(verify drug protocol)
- Random
 Steady state can be achieved after an individual
consistently receive a drug with the duration of 5 -7 half-
life

II. Specimen Type

- Serum : no gel
- Plasma : heparinized
o EDTA, citated, oxalated not accepted
- Whole blood
- Saliva – can detect recent drug use/exposure
DRUG GROUPS
D. ELIMINATION  Cardioactive  Antiasthmatic
- Irreversible removal of a drug or its metabolites from the  Antibiotics  Immunosuppressive
body  Antiepileptic  Antineoplastic
- Hepatic metabolism  Psychotherapeutic  antihypertensive
- Renal filtration A. CARDIOACTIVE
- Other: skin, lungs, mammary glands, and salivary glands Drugs that activate the cardiac muscle; use to treat heart
 Functional changes in organs can affect rate of elimination failure, arrhythmia, atrial fibrillation
I. Digoxin – digoxigenin (urine metabolite)
- i.e. Hepatic disease with a loss of tissue result in slow rate
of clearance with a longer half-life  Used to treat CHF (congestive heart failure)

pg. 7
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 Peaks draw at 2 hours post dose  Tricyclic Antidepressants “TCAs”

 Inhibits sodium and potassium transport within the - Desipramine (parent is imipramine)
heart - Nortriptyline (parent is amitriptyline)
 Allows for better cardiac muscle contraction and - 2-hydroxy-desipramine (parent is desipramine)
rhythm  Clozapine – Clozaril (neutropenia, cardiomyopathy, etc)
 Major cardiac glycoside -to treat schizophrenia; can cause neutropenia,
 Alters the force of contraction through its effect on agranulocytosis, seizures, myocarditis, cardiomyopathy
the ATPase pump in heart muscle  Olanzapine – is a thienbenzodiazepine derivative that
 Toxicity: nausea, rapid heart rate, visual impairment effectively treats schizophrenia, acute manic episode, and
II. Lidocaine – monoethylglycinexylidide, glycinexylide (2 the recurrence of bipolar disorders
active metabolites)  Fluoxetine – is not chemically related to the tricyclic
 Used to treat premature ventricular contractions antidepressants, but has a similar effect by blocking
 Affects the timing of cardiac contraction uptake by nerve terminals in the CNS and by platelets; use
 Binds to alpha-1-acid glycoprotein to treat OCD, bulimia etc.
 Metabolize in the liver
III. Quinidine – 3-hydroxyquinidine 9active metabolite)
 Used to treat cardiac arrhythmic problems
 Inhibits sodium and potassium channels
 Prevents arrhythmias, atrial flutter, and fibrillation
IV. Procainamide
 Used to treat cardiac arrhythmic situations
 Blocks sodium channels
 Affects cardiac muscle contraction
 Often measured with NAPA E. ANTIASTHMATIC
 N-Acetyl procainamide -active metabolite  Examples include theophylline and theobromine
V. Disopyramide (Norpace)  Have to relax bronchial smooth muscle – bronchodilator
 Is another drug used to treat cardiac arrhythmias  All are methyl xanthine derivatives – use for relief and
 Commonly used as a quinidine substitute when prevention of asthma
quinidine adverse effects are excessive  dimethyl xanthine – teobromina and teofillina
 Serum concentration is peaking at 1-2 hours  trimethyl xanthine - caffeine
VI. Propranolol – OLOLs (classified as beta blockers)
 Is prescribed for atrial and ventricular arrhythmias
and hypertension
B. ANTIBIOTICS
I. Aminoglycosides
 Gentamycin (Micromonospora purpurea),
tobramycin (Streptomyces tenebrarius), amikacin,
and kanamycin (Streptomyces tenebrarius)
 Use in the treatment of aerobic, gram negative F. IMMUNOSUPPRESSIVE
bacilli infections, staphylococci, mycobacterium I. Cyclosporine
tuberculosis  Whole blood is the specimen of choice, since it
II. Vancomycin sequesters in the RBC
 Inhibits cell wall synthesis II. Tacrolimus (Progaf)
 Produced by soil bacterium Amycolatopsis orientalis  Prevents rejection of liver and kidney transplants
 Red man syndrome, nephrotoxicity, autotoxicity G. ANTINEOPLASTICS
C. ANTIEPILEPTIC “AEDs” I. Methotrexate
 Most first and second – generation AEDs used to treat  Inhibits DNA synthesis
seizure disorders and epilepsy H. ANTIHYPERTENSIVE
First generation Second generation Used in treatment of high blood pressure; dilates blood vessel
 Phenobarbital –  Felbamate  Calcium channel blockers (-dipine), beta-blockers –
Barbiturate Primidone is a  Gabapentin – blocks epinephrine(-olol), ACE inhibitor – inhibits
proform; use to treat all monotherapy angiotensin 2(-pryl)
types of seizure  Levetiracetam I. Sodium nitroprusside
 Phenytoin – Dilantin  Oxcarbazpine -  Used for short-term control of hypertension
 Valproic acid – Depakene Licarbazepine
 Carbamazepine – Tegretol  Tigabine
 Primidone  Topiramate
 Zonisamide
D. PSYCHOTHERAPEUTIC
 Lithium -to prevent mania; has narrow therapeutic range

pg. 8
 CLINICAL CHEMISTRY

- Salicylate (aspirin) is considered toxic at a

serum level of >90 mg/dL 6 hours following
ingestion. The time since ingestion must be
known to determine severity of toxicity.
 Treatment for overdose:
- Involves neutralizing and eliminating the
excess acid and maintaining electrolyte
balance.
- Renal clearance of salicylate can be increased
I. MAJOR TRANQUILIZER by forced alkaline diuresis.
For the treatment of anxiety, fear, tension, and agitaion II. Acetaminophen
I. Barbiturates (CNS depression)  is a commonly used analgesic drug.
- Ultra-short acting – sodium pentothal; use in  USA name (USAN)
induction of anesthesia  Severe hepatotoxicity
- Short acting – pentobarbital, secobarbital –  Toxicity:
sedatives (10-15 mins onset, 3-4 hours duration) - Acetaminophen, if present in serum at
- Intermediate acting – amo-, beta butabarbital – for 300mcg/mL 2-4 hours after ingestion, induces
inducing and maintaining sleep (45-60 mins onset, hepatic toxicity.
6-8 hours duration)  Antidote: N-acetylcysteine
- Long acting – phenobarbital – for seizures (30-60
mins onset, 10-16 hours duration)
II. Benzodiazepines
a) Diazepam (valium)
b) Chlordiazepoxide (lithium)
c) Lorazepam (Ativan)
J. IMMUNOSUPPRESSIVE
Lowers the body’s immune system; monitoring of these drugs
are important to prevent organ dejection; use to treat
autoimmune disease
I. Cyclosporine
 Whole blood is the specimen of choice, since it
sequesters in the RBC
II. Tacrolimus (Progaf)
 Prevents rejection of liver and kidney transplants
III. Sirolimus (rapamycin) (under macrolides)
 Is an antifungal agent with immunosuppressive
activity
 Treat rare lung disease: Lymphagioleiomyomatosis
 Compound use to coat coronary stent
IV. Mycophenolate mofetil (Mycophenolic Acid)
 Is a prodrug that is rapidly converted in the liver to
its active form of mycophenolic acid (MPA)
 Lymphocyte proliferation inhibitor
K. ANTINEOPLASTICA
I. Methotrexate (MTX)
 Inhibits DNA synthesis
L. ANTI-INFLAMMATORY
I. Salicylates
 Aspirin (Acetylsalicylic acid)
- is a commonly used analgesic, antipyretic, and
anti-inflammatory drug
- anti-thrombotic
 Adverse effects:
- Interference with platelet aggregation and
gastrointestinal function.
- There is also an epidemiologic relationship
between aspirin, childhood viral infections
(e.g., varicella and influenza), and the onset of
Reye’s syndrome
 Toxic effect:

pg. 9