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| Pharmacology | 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 |
| Pharmacokinetics (PK) | The study of the body's effect on the druge. This includes the processes of absorption, distribution, metabolism and excretion of drugs |
| Pharamcodynamics (PD) | The study of physiological effects on drugs on the body |
| Therapeutic Range | Range of serum drug concentrations associated with therapeutic effect (limited or no toxicity) in majority of patients |
| Steady State | The equilibrium achieved during chornic dosing when the rate of the drug input equals the rate of the drug excretion |
| Trough | Lowest serum drug concentration following a single dose or at a steady state within a dosing interval. The trough concentration generally occurs prior to administration of the next dose |
| Peak | Highest serum drug concentration that occurs following a single dose or at steady state within a dosing interval. If a drug is given orally, the time to peak concentration is deteremined by the rate of absorption and the rate of elimination. The exact peak concentration cannot be deteremined without frequent serial blood sampling |
| Half-Life | The time required for serum drug concentration to decrease by 50% |
| Minimum Effective Concentration (MEC) | Minimum serum druve concentration necessary to produce a desired therapeutic effect |
| Minium Toxic Concentration (MTC) | Minimum serum drug concentration necessary to begin producing a toxic effect on the body |
| Optimal Dosing Cycle | Trough should be reached immediately before the next dose Should not fall below MEC Peak should not rishe higher than MTC Drug administrered once every half-life Steady state should be after approx dosing of 5 half-life cycles Blood concentrations greater than MTC, patient is at risk of toxic effects Blood concentrations less than MEC, patient at risk for disorder the drug was meant to treat |
| Bioavailability | Fraction of the drug absorbed into the systemic circulation Dependent on route of administration Water-soluble drugs frequently weakly bound to serum proteins |
| First Pass Effect & Liver Biotransformation | After oral administration, drugs pass through stomach routed directly to the liver via portal circulation In the liver, drug extensively metabolized before reaching the systemic circulation. Is called first pass effect Liver is principal organ responsible for drug metabolism Drugs converted to more polar, water soluble molecule by altering chemical structure through oxidation, reduction, or hydrolysis reactions Biotransformation increases solubility drug to be more readily excreted in urine |
| Rate of Absorption | Absorption rate usually much greater than its rate of elimination Oral drugs formulated with larger doses to be effective target systemic sites after metabolic breakdown (First Pass Effect) Drug formulations provide sustained release permitting oral medicine to be taken less frequent intervals Drugs administered intravenously (IV) formulated much lower doses since 100% directly enters bloodstream avoiding first pass metabolic effect |
| Conditions affecting rate of absorption | Abnormal GI motility Diseases or infections of the GI tract Food (presence or absence depending on the particular drug) Co-administered drugs afect gastric abosrption by altering pH |
| Synergistic | Drug that enhances the therapeutic effect of another drug |
| Antagonistic | Drug administered that diminishes the action of another drug, this may be beneficial or harmful |
| Processes involved in drug distribution | Unless a drugs site of administration coincides with its site of action, drug must be translocated to its site of action. Known as distribution Drug enteres the systemic circulation, simultaneous distribution to body tissues, potential metabolism, and eventual elimination by clearing organs. Blood is the vehicle which drugs are distributed to all organs and fluid compartments Free fraction of the drug is the form capable of generating a therapeutic effect A fraction of drugs will bind to proteins in the bloodstream. Changes in the protein-binding characteristics can influence the distribution and elimination of a drug |
| Process involved in drug excretions | Kidney is primary organ in drug excretion. Both the glomeruli and tubules much be functioning for optimal drug elimination Drugs that are water soluble or can be made water soluble are eliminated from the body via urine Excretion of a drug can also occur through intestinal or pulmonary routes. Drugs and their metabolites may be excreted by bile, feces, saliva, expired air, and breast milk. Urine is the most frequently assayed to indicate previous drug exposure |
| Cardioactive | Class of drugs used to treat heart conditions Examples: Digoxin, Digitoxin, Lidocaine, Quinidine, and Procainamide |
| Antibiotics | Class of drugs that prevent the growth of a wide range of bacteria Example: Aminoglycosides and Vacomycin |
| Antiepileptic | Class of drugs that is effective against epilepsy Example: Phenobarbital, Phenytoin, Valproic Acid |
| Psychoactive | Class of drugs that is effective at affecting the mind or behavior Example: Lithium and Tricyclic Antidepressants |
| Bronchodilators | Class of drugs that are effective at dilating the air passages of the lung Example: Theophylline |
| Digoxin and Digitoxin | Cardiac glycosides used in the treament of cardiac arrhythmia (abnormal heart rhythm) |
| Lidocaine, Quinidine, and Procainamide | Used to correct ventricular arrhythmia and to prevent ventricular fibrillation (uncoordinated contraction of the cardiac muscle of the ventricles in the heart) |
| Aminoglycosides | Group of chemically related antibiotics used for the treament of infections with gram negative bacteria that are resistant to less toxic antibiotics |
| Vancomycin | A glycopeptide antibiotic that is effective against select gram positive bacteria. Because of its poor oral absorption, it is administered by IV infusion |
| Phenobarbital | A slow acting barbituate that effectively controls several types of seizures. Oral absorption is slow; peak concentration occurs in approximately 10 hours after dose |
| Phenytoin (Dilantin) | A fast acting drug used to treat a varieity of seizure disorders. It is also used as a short term prophylactic agent in brain injury to preven loss of functional tissue. Primarily administered orally |
| Valproic Acid (VPA) | A slow to fast acting drug used for treatment as an anticonvulsant and mood stabilizing drug, primarily in the treatment of epilepsy and bipolar disorder (a category of mood disorders). It is also used to treat migraine headaches and schizophrenia |
| Lithium | An orally administered drug used to treat manic depressive illness. Absorption is complete and rapid |
| Tricyclic Antidepressants | Are a class of drugs used to treat depression, insomnia, and extreme apathy |
| Theophylline | A commonly administered aerosol drug used in the treatment of asthma and other Chornic Obstructive Pulmonary Disorder |
| Advantages of therapeutic drug monitoring | Detection of non-compliance Detects patients undergoing changes in drug disposition characteristics Can be used to adjust therapeutic regimens in times of continous physiological change Establishes the dosage for baseline therapeutic concentration |
| Administrative Data needed | Patient name, SSN, DOB, sex Date/time of collection Date/time of last dose Amount of last dose Name of drug (both generic and trade name if possible) Patient diagnosis |
| Sample Requirements | Non-hemolyzed serum Non-hemolyzed plasma- Use the appropriae collection tube for the drug tested (usually red or dark blue top) Urine |
| Timing | Follow IAW protocols policy for hos soon a sample should be drawn before/after a dose |
| Storage | Samples should be centrifuged and serum/plasma removed from the cells as soon as possible after collection Most drugs/metabolites are stable at room temperature for several days |
| Analytical and Practical Requirements of an effective therapeutic drug monitoring | Assay methods used for TDM should be accurate and reproducible Medical staff should be informed about therapeutic and toxic ranges, required sample volume and collection tube specifications Time and date of collection of the patient sample and of the last dose should be noted To assess steady-state conditions, the length of time a patient has been on a particular regimen should be known Steady state is unchanging equillibrium Calculations to determine the numbers of doses needed to reach steady state endure complex advanced mathematical equations |
| Common drugs of abuse classes | Psychostimulants Cannabinoids CNS depressants Opoids Pyschedlics Sports enhancing drugs General stimulants Inhalants and anesthetics |
| Psychostimulants | Cocaine and amphetamines Dextroamphetamines Methamphetamines MDMA (ecstasy) |
| Cannabinoids | Marijuana Hashish |
| CNS depressants | Barbiturates Alcohol Benzodiazepines |
| Opoids | Morphine Codeine Oxycodone Heroin Opium (all derived from the poppy plant) |
| Psychedelics (hallucinogens) | LSD Ecstasy and other designer amphetamines Peyote (Mescaline) Psilocybin Phenylcyclidine (PCP, Angel Dust) |
| Sports enhancing drugs | Anabolic Steroids hGH Etc |
| General Stimulants | Nicotine Tobacco Caffeine |
| Inhalants and Anesthetics | Volatile Nitrites Organic Solvents |
| Effects of Alcohol | Consumed in excess, alcohol distrupts the chemical balance and controlling reasoning and judgment Most commong drug abuse seen in the emergency room |
| Sources of Alcohol | Fermentation- certain yeasts and bacteria anaerobically metabolize sugar into ethanol Distillation- Process in which solutions containing alcohol are heated and the vapors collected and condensed back into liquid |
| Major uses of Alcohol | Alcoholic beverages (beer, wine, hard liqour, etc) Solvents (perfumes, varnish, mouthwash, antiseptic, cough medicine, etc) Antidote for methanol (CH3OH) poisoning |
| Legal Issues of Alcohol abuse | A Blood Alcohol Concentration (BAC) result of 0.08% w/v (80 mg/dL) is legal evidence for a criminal conviction for intoxicated driving (DWI/DUI) A blood alcohol test with any detectable ethanol present while on duty is grounds for disciplinary actions by the Chain of Command or Military Police per the UCMJ |
| Metabolism of Alcohol | Ethanol is rapidly absorbed from the gastrointestinal tract. Approximately 20% is absorbed into the blood from the stomach and 80% is absorbed from the small intesting 90-98% of ethanol is oxidized to acetaldehyde by alcohol dehydrogenase Acetaldehyde is converted to acetate by acetaldehyde dehydrogenase and is ultimately broken down to carbon dioxide and water |
| Effects of Alcohol | Muscular system- coordination is impaired Circulatory System- blood vessels dilate causing increased heat loss from the body Respiratory System- small doses stimulate respiration (increased breathing rate) Nervouse System- Lowered inhibition at low doses followed by mental confusion and uncontrolled mood swings at higher levels Digestive System- Increase digestive secretions cause stomach irritation (increased pH levels) Endocrine- Secretions of various hormones may be altered |
| Effects of Alcohol on redproductive system | In women: Overuse during pregnancy can lead to miscarriages, infant deaths, and smaller, weaker newborns Birth defects include the Fetal Alcohol Syndrome, a condition that can result in mental and growth retardation In males: Alcoholism leads to importence and decreased testosterone levels |
| Treatment for Alcohol | Detoxification: Clear the stomach Withdrawal may cause delirium tremens (DTs)- a condition associated with tremors,tachycardia, hypertension, diaphoresis, hallucinations, delusions, disorientation, and possibly seizures After-care for chornic abuser: Antabuse Nutritious diet supplemented with vitamins Behavior modification to teach avoidance and coping mechanism |
| Toxicology | Science of poisons and their effects on the body |
| Poison | Chemical agent that when ingested, injected, inhaled, or absorbed can cause tissue injury or death |
| Dose | Amount of chemical agent introduced into the body. For many medications, the right dose differentiates poison from remedy |
| Lethal Dose 50 (LD50) | Quantity of a substance required to cause death in 50% of the sample group |
| Therapeutic Dose | Amount of substance that will produce a desired pharmacological effect |
| Drug of Abuse | Drug used in excess or for non-therapeutic reasons. These drugs have high abuse potential and users can become addicted |
| Drug Addiction | A severe physiological degree of drug dependence with a continuing involvement in durg use. Addictive users are compulsively seeking to use a substance, regardless of the potentially negative social, phsyiological and physical consequences |
| Mechanisms that affect Toxicity | Interference with critical enzyme actions Blockage of oxygen usage and transport Interferes with cell function Hypersensitivity reactions |
| Factors that affect toxicity | Nature of toxicant Route of exposure Dosage Drug interactions Biological variables |
| Clinical Toxicology | Analysis of drugs, heavy metals and other chemical agents in tissue, blood or body fluids to support patient care |
| Forensic Toxicology | Addresses the effects of potentially toxic substances on the living or as determination of a cause of death to aid medico-legal investigations |
| Enviromental Toxicology | Considers the harmful effects of exposure to chemicals present in the environment from natural or industrial sources |
| Medico-Legal Aspects | Cases are those in which possibility of criminal poisoning exists or cases in which legal action may be taken in order to determine liability Chain of Custody- The unbroken documentation trail of accountability that gaurantees a samples physical security. It includes who came in contact with a sample and its aliqouts, why and where it occured |
| Specimen handling for toxicological examination | Legal request require a Chain of Custody Collection procedures: Proper specimene colection and preservation is required Properly label and seal the container Sign and date appropriate chain of custody form |
| Transporation and storage | Special precautions are necessary Specimens and other eveidence must be in custody of appropriate personnel at all times or in a locked container to avoid any legal objections Documentation form must include detail description of collection container in addition to signature of transporting and receiving individuals |
| Chemcial analysis | Analysis is run in duplicate alongside known controls Proper documentation must be annotated with testing individual's signature Tested specimen is stored in locked freezer per local SOP guidelines |
| Reporting Results | Medical Results- Results for patient treatment purposes only that are released to requesting Health Care Provider (HCP) or attending nurse Legal results- Registrar (from Patient Administration) is the only individual authorized to receive toxicological results. Legal toxicology results are NEVER given over the phone |
| Acetominophen | Common over the counter analgesic medication Predominantly metabolized to glucuronide and a small amount is metabolized by cytochrome p450 enzyme in the liver. Poisoning, a large amount of cytochrome p450 toxic metabolite is produced that reacts directly with the hepatic macromolecules causing liver damage Renal damage occurs less frequiently by the same mechanism Alcoholics typically have elevated levels of cytochrome p450 and are more prone to acetominophen poisoning |
| Carbon Monoxide | Toxicity is a consequence of cellular hypoxia Binds to hemoglobin with an affinity 200 times greater than O2. Product is called carboxyhemoglobin CO directly inhibits cyochrome oxidase, further disrupting cellular function |
| Heavy Metals | Environmental toxins that are frequent clinical importance include lead (Pb), mercury (Hg) and aresenic (As) |
| Lead (Pb) | Is toxic to multiple organ systems in the human body Associated with alteraions in cellular and mitochrondrial membranes, diminished neurotransmitter and heme synthesis and impede nucleotide metabolism Frequently found in paint (1970 and before) and used to be an additive in gasoline |
| Mercury (Hg) | Particularly toxic to the Central Nervous System (CNS) Abundant in tune, teratogenic Inorganic mercuric salts are corrosive to the skin, eyes, and GI tract and are nephrotoxic |
| Organophosphatase (OP) | Compounds inhibit the critical enzyme acetylcholinesterase (AChe) found in the nerve endings, red blood cells (RBCs) and butyrylchoinesterase in the blood Bloacde of AChE leads to the accumulation of excessive acetylcholine at the nerve endings causing symptoms such as limb weakness or numbness, loss of memory, vision, and/or intellect, headache, cognitive and behavioral problems and sexual dysfunction |
| Salicylates | Common over the counter analgesic medication (Aspirin) Central stimulation to the respiratory center results in hyperventilation, leading to respiratory alkalosis, Secundary consequences from hyperventilation include dehydration and compensatory metabolic acidosis Intracellular effects cause interruption of glucose and fatty acid metabolism, which contribute to metabolic acidosis |
| Qualitive Procedures | Rapidly and easily performed, colorimetric result often based upon immunoassay spot tests, often used in Point of Care Testing Provide presumptive qualitative evidence for the presence or absence of the tested drug or druge metabolite Any positive result must be followed up with a more specific quantitative method |
| Enzyme Multiplied Immunoassay Technique (EMIT) | Limited Ab is mixed with patient Ag and enzyme labeled Ag*. Ags compete for Ab binding sites and Ab-Ag binding inactivates enzyme label. Substrate is then added to the assay and only free, unbound Ag- enzyme can react with substrate. Enzyme product is quantified |
| Fluorescece Polarization Immunoassay (FPIA) | The amount of polarized fluorescent light detected when the fluorescent label is excited with polarized light. Fluorescent label can be attached to Ag or Ab Often used as a semi-quantitative screening procedures for drugs of abuse |
| Gas Chromatography/ Mass Spectometry (GC/MS) | Expensive, labor intensive procedure that is capable of determining a broad spectrum of drugs. It is widely used for both qualitative and quantitative drug analysis Established forensic confirmation procedure for drug abuse quantitation |
| Atomic Absorption Spectroscopy | An instrument often used to detect the concentration of a particular metal element in a sample Can be used to analyze the concentration of over 62 different metals in a solution |
| Gas Chromatography/ Mass Spectrophotometry (GC/MS) in testing for Alcohol | Confirmation procedure in which alcohol and its metabolites are separated based on their physical properties Supports medico-legal situations Specimen of choice: Whole blood with fluoride as a preservative |
| Enzymatic Methods (Alcohol Dehydrogenase) in testing for Alcohol | Ethanol and NAD in the presence of alcohol dehydrogenase yield acetaldehyde and NADH Speciment of choice: Serum or plasma with oxalate, citrate or heparin added as a preservative |
| Cholinesterase | Is measured to indicate poisoning instead of tissue damage Found in plasma arises from liver, heart and white matter of the brain Has no known function |
| Clinical Importance of Cholinesterase | Acts as a surrogate for acetyl-cholinesterase, which is active at neural synapses Plasma Cholinesterase and ACHe hydrolyze esters of choline Persons exposed to organophsphate insecticides as well as patients anesthetized with succinly-choline, rely on their cholinesterase enzymes to destroy the poisons or drug and restore synaptic function |
| Cholinesterase Assay Testing | Substrate used to assay plasma cholinesterase is butyryl-thiocoline, which is hydrolyzed to butyric acid and thiocholine. Thiocholine is then measured by producing a colored derivative with dithiobis-nitrobenzoate Acetylcholinesterase (AChE)- Critical enzymes primarily in the RBC's and neural synapses Pseudocholinesterase (Butyrylcholinesterase BuChE)- Found primarily in the liver and serum Preferred sampe is serum. Hemolysis is not acceptable because erythrocytes contain acethycholinesterase which acts on the same substrate as PChE |
