Dental Toxicology (6 questions) Flashcards
Father of toxicology who said “the dose makes the poison” “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from remedy”
Theophrastus Phillippus Aureolus Bombastus von Hohenheim aka Paracelsus
In 1930 the name of Food, Drug, and insecticide Administration shorted to
Food and Drug Administration (FDA)
1960’s Thalidomide disaster, drug used for?
nausea associated with pregnancy. Sold over the counter. Found to be teratogenic. Caused phocomelia (underdeveloped limbs).
Toxicology
is the study of the adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem, including the prevention and amelioration of such adverse effects”-Society of Toxicology
FDA (Food and Drug Administration)
control/regulates drugs used for human and veterinary drugs, dietary supplements, medical devices, food products, cosmetics, products that emit radiation.
Toxicants
substance that produces adverse biological effects of any nature
posisons
toxicant that cause immediate death or illness when experienced in very small amounts
toxins
specific proteins produced by leaving organisms
Bioaccumulation
The accumulation of a substance, such as a toxic chemical, in various tissues of a living organism. Bioaccumulation takes place within an organism when the rate of intake of a substance is greater than the rate of excretion or metabolic transformation of that substance. Happens in the SAME ANIMAL.
Biomagnification
The increasing concentration of a substance, such as a toxic chemical, in the tissues of organisms at successively higher levels in a food chain. DIFFERENT ANIMAL BUT SAME FOOD CHAIN. Process of taking non-toxic chemical to a chemical one.
e.g. PCB (Polychlorobiphenyls in Great Lakes), Mercury in Minimata bay in Japan)
Bioactivation
The metabolic activation of xenobiotic compounds into reactive, toxic compounds. Body turns it toxic. e.g. tylenol.
Detoxification
physiological or medicinal removal of toxic substances from the body
What form of Mercury is toxic?
Dimethylmercury (organic)
Fluoride antidote?
1% CaCl2 or calcium gluconate or milk
Tylenol target organ?
maximum adult use?
What entitiy cause toxicity?
Antidote?
Liver
4g in 24 hours
NACQI
N-acetylcysteine (NAC)
Cocaine antidote?
no specific antidote
Antidepressants antidote?
No specific antidotes.
Cardiovascular drug: Digoxin antidote?
Digiband
Cardiovascular drug: Calcium channel antagonists?
Antidote: Activated charcoal within 1-2 hours, IV calcium chloride in serious poisoning, positive inotropes, insulin
Name 3 regulatory agencies
FDA
EPA
OSHA
EPA (environmental protection agency)
the objective of the EPA is to: ‘use its best endeavours – a) to protect the environment; and b) to prevent, control and abate pollution and environmental harm.’
OSHA (Occupational Safety and Health Administration)
OSHA assure safe and healthful working conditions for working men and women by setting and enforcing standards and by providing training, outreach, education and assistance.
State the year in which FDA established?
1930
Ex. of Biomagnification in Great Lakes and marine life?
PCB (a pesticide) aka persistent organic pollutants are endocrine disruptures. Chemicals get magnified as they go to higher levels in the food chain. e.g. zooplankton feed off phytoplankton thus more PCB conc. in that.
More mercury in large fish like Shark in marine life.
Explain biotransformation and processes involved in it?
Biotransformation- chemical alternation of chemicals such as nutrients, aa, toxins, and drugs in the body.
Lipophilic chemical–>Hydrophilic Chemical–>readily excreted
Accumulation–>Phase I–> Phase II
LD50
Dose that is lethal in 50 % of the exposed animals
Median Toxic dose (TD50)
toxic dose in 50 % of the population or Lethal dose (LD50)
Median effective dose (ED50)
effective dose in 50 % of the population
Therapeutic Index (Window)
margin of safety;
how selective a drug is in producing its desired effects over adverse effects
Additive Effect
1+1 = 2
if two compounds that causes similar types of toxicity together cause an effect that is sum of the individual effects
Toluene & p-xylene
Synergism
1=1 =5
if two compounds together causes an effect that is stronger than additive effect of the two
Ethanol & CCL4 & Tylenol
Potentiation
0+1 = 3
if one of the compounds is not toxic by itself, but enhances the toxicity of another compound
2-propranolol & CCl4
Antagonism
1+0 = 0
Subacute: exposure period?
1-14 days
Subchronic: exposure period?
14-28 days
Chronic toxicity: exposure period?
6-24 months
Preclinical studies
sdfsss
four phases of clinical FDA evolution of New Drugs
Phase I:
Effect of drug under investigation in healthy volunteer human subjects (20-80)
Determine toxicity and dose, PK
Phase II:
Effectiveness of drugs in human subjects for particular indication
Well controlled, monitored, small studies in patients [several hundred (100-300)]
Phase III:
Double blind study, compares effect against standard treatment
Extrapolation to general population for risk benefit analysis & information for physician labeling
Several thousand (1000-3000) subjects are involved
Phase IV:
Post marketing surveillance
Institutional Review Board (IRB):
Ethical treatment & full consent for studies
Roseman has IRB (members are from Faculty, Staff, Community)
Pb-drug example? Target organ? Toxicity mechanism? Trreatment/Antidote?
Drug example: piston-engine aircrafts Coal-fired plants (major source in environment) Lead-based paints (old houses) Auto emissions (TEL, now rare) Toxicity mechanism: Coal-fired plants (major source in environment) Lead-based paints (old houses) Auto emissions (TEL, now rare) Target organ: Encephalopathy (acute, emergency), Anemia, CNS deficits Treatment/Antidote: Chelation Therapy (IV)
Mercury (Hydragyrum) sources
Contaminated drinking
dental amalgam, water, Coal-fired power plants (~13 tons/year), Food (fish, waterfowl etc.) contaminated with mercury, Mercury thermometers, Leaching of mercury from badly fitting dental amalgams, Vaccines containing thimerosal, Button cells (battery)
Most toxic form of mercury?
Dimethylmercury (organic)
Hg Toxicity Mechanism
Interacts with SH groups in enzymes, causes necrosis of proximal tubular epithelium, Organic mercury is more toxic to CNS
Hg target organ?
Toxicokinetics: Absorbed from respiratory tract, GIT and organic form from skin also; Metabolised to divalent mercury; Distributed mainly to kidney, brain; Excreted in urine and faeces (inorganic) or in faeces (alkyl Hg)
Hg antidote
chelation
Hg Antidote MOA
Chelation Dimercaprol
Acetaminophen (Tylenol)-poisoning signs
Phase 1- No symptoms or mild GI symptoms such as vomiting
Phase 2- Right upper quadrant abdominal tenderness, Tachycardia, Hypotension
Phase 3- Jaundice, Coagulopathy, including GI bleeding, Hepatic encephalopathy
Phase 4- Resolution
Acetopminophen target organ
Liver and kidney
Acetominophen Poisoning-Antidote
Activated charcoal (AC) can adsorb APAP and is useful as a decontaminant if given within 1 hr of ingestion
N-acetylcysteine (NAC) is the specific antidote - p.o. usually given in cola drinks to mask taste
NAC reacts directly with NAPQI and prevents cellular damage
NAC is a glutathione precursor»_space; repletes glutathione storage»_space; conjugate NAPQI
NAC has some non-specific cellular protective effects, anti-oxidant effects
Effective when given within 8 hrs of ingestion
Sedative Hypnotics-
benzodiazepines
barbituates
Sedative Antidote
Flumazenil Antidote to Benzodiazepine Overdose/Poisoning
Barbituates have no antidote
Opiods (Morphine, hydrocodone, methadone, oxycodone) antidote?
non-selective opioid antagonist
e.g. Naloxone, Naltrexone
CVS drugs (Cardiovascular drugs)-Calcium channel antagonists; antidote?
Activated charcoal within 1-2 hours, IV calcium chloride in serious poisoning, positive inotropes, insulin
CVS drug-Digoxin; antidote?
Digiband
Tricyclic Antidepressants; antidote?
No specific antidotes; activated charcoal, gastric lavage, treated with symptomatic care and intravenous sodium bicarbonate
Stimulants and Street Drugs
Cocaine Amphetamine Methamphetamine Heroin Lysergic acid diethylamide (LSD) Khat Bath salts
Cocaine: acute toxicity?
Prevents reuptake of DA» increased DA in CNS
Cocaine: antidote?
No specific antidote
Treatment is symptomatic
Convulsion > diazepam
Myocardial ischemia > nitrates, beta blockers, Ca channel blockers
Hypertension > nitroprusside, phentolamine, Ca++ channel blockers
Methods for decontamination
Activated charcoal Emetics Cathartics Gavage Whole bowel irrigation Enhancing elimination (Hemodialysis/hemoperfusion, Urine pH manipulation)
Activated charcoal advantage/dis.
Pro: Adsorbs substances to prevent systemic absorption
Con: Mostly aromatic molecules & gases are adsorbed.
Limited value after 1-2 hours of ingestion
Emetics (a medicine or other substance that causes vomiting)
Syrup of Ipecac
Should be administered with 30-60 minutes of ingestion
Orogastric Lavage (stomach pumping or gastric irrigation, is the process of cleaning out the contents of the stomach)
Removes stomach content through a large bore tube until the return is clear
Cathartics ( a substance that accelerates defecation)
MOA: increases motility of intestine, decreases intestinal residence time
Agents:
Sorbitol or Magnesium citrate
List chemicals/drugs for which hemodialysis may be helpful?
Amphetamines, antibiotics, isoniazid, phenobarbitol, salicylates, thiocyanates
Explain how urine pH manipulation helps elimination of toxicant?
Mechanism of Action: ionic chemicals are trapped in urine (prevent reabsorption)
Acidified urine will enhance elimination of weak bases
Alkalinized urine will enhance elimination of weak acids
State few services that are provided by poison control centers?
Assessment, treatment recommendations, signs and symptoms, decontamination recommendations, locating antidotes/antivenoms, pill and toxidrome identification
Toxidrome: The chemical structure of a compound. Lab tests take too long for a diagnosis, in the clinic we want to use signs and symptoms as a quick way to diagnose the chemical grouping/toxidrome/category of toxin in order to treat the patient quickly.
emesis
vomiting
emesis induced by
ipecac tincture
antidote of morphine
naloxone
antidote of diazepam
flumazenil
overdose scenario morphine
urine pH manipulation
amphetamine overdose
urine pH manipulation
tricyclic antidepressant poisoning
activated charcoal
overdose of delayed release drugs
magnesium citrate
polyethylene glycol lavage solution
Patient tried to kill themselves, doesn’t remember what they took. Have symptom of nausea and after 24 hours lab results showed serum of ALT(Alanine transaminase) in blood. What drug did they try to overdose on?
Acetaminophen (Tylenol)
Diazepam
Flumazenzil
Acetaminiphin convertered to NAQI
Bioactivation
TI
TI=LD50/ED50
Nalaxone (NARCAN)
opiods
Succimer (CHEMET)
heavy metal
Calcium (IV)
CCBs
Overdose situation treated with acidification of urine using ammonium chloride
Morphine (Weak base)
ALT and AST is a ___ specific enzyme
liver
