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level: Level 3

Questions and Answers List

level questions: Level 3

Question	Answer
4 TYPES OF ANTAGONISM	1 Functional Antagonism 2 Chemical Antagonism / Inactivation 3 Dispositional Antagonism 4 Receptor Antagonism
o Occurs when TWO CHEMICALS COUNTERBALANCE EACH OTHER by PRODUCING OPPOSITE EFFECTS on the same physiologic function. o For example, the marked all in blood pressure during severe barbiturate intoxication can be effectively antagonized by the intravenous administration of a vasopressor agent such as norepinephrine or metaraminol.	Functional Antagonism
o simply a CHEMICAL REACTION BETWEEN TWO COMPOUNDS that PRODUCES a LESS TOXIC PRODUCT o For example, chelators o metal ions decrease metal toxicity and antitoxins antagonize the action of various animal toxins	Chemical Antagonism / Inactivation
o OCCURS WHEN the ABSORPTION BIOTRANSFORMATION, DISTRIBUTION, or EXCRETION of a CHEMICAL is ALTERED so that the CONCENTRATION and/or duration of the CHEMICAL at the target organ are DIMINISHED o depend on how fast the victim or one person to do this ADME o For example madaming laman ang tiyan then matagal ang absorption ng poison	Dispositional Antagonism
o occurs when TWO CHEMICALS THAT BIND TO THE SAME RECEPTOR produce LESS OF AN EFFECT WHEN GIVEN TOGETHER than the ADDITION OF THEIR SEPARATE EFFECTS or when one chemical antagonizes the effect of the second chemical o Receptor antagonists are often termed blockers. o For example; ANTIHISTAMINE it will bind to histidine decarboxylase o Binding of enzyme and active site	Receptor Antagonism
§ A STATE OF DECREASED RESPONSIVENESS to a TOXIC EFFECT OF A CHEMICAL resulting from prior exposure to that chemical or a structurally related chemical	Tolerance
Two major mechanisms are RESPONSIBLE FOR TOLERANCE:	1 due to a DECREASED AMOUNT OF TOXICANT REACHING THE SITE where the TOXIC EFFECT IS PRODUCED (dispositional tolerance) 2 due to a REDUCED RESPONSIVENESS of a TISSUE to the CHEMICAL
CHARACTERISTICS OF EXPOSURE The major routes (pathways) by which toxic agents gain access to the body are:	1 gastrointestinal tract (ingestion), 2 lungs(inhalation), 3 skin (topical, percutaneous, or dermal), 4 parenteral (other than intestinal canal) routes.
CHARACTERISTICS OF EXPOSURE Descending order of effectiveness/can give toxic effects:	1) IV, 2 Inhalational, 3 Intraperitoneal, 4 Subcutaneous, 5 Intramuscular, 6 intradermal, 7 oral and 8 dermal unless broken
DURATION AND FREQUENCY OF EXPOSURE 1) defined as EXPOSURE TO A CHEMICAL OR LESS THAN 24 HR. 2) refers to CONTINUOUS EXPOSURE OR LESS THAN 24 H, MOST FREQUENTLY 4 H. 3) Repeated exposure for 1 month or less 4) 1-3 months (REPEATED EXPOSURE FOR SEVERAL WEEKS OR MONTHS) 5) 3 months- years and above.	. 1 Acute 2 Acute exposure by inhalation 3 Subacute 4 Subchronic 5 Chronic
Repeated exposure is divided into three categories:	1 subacute, 2 subchronic, and 3 chronic.
Correlative relationship of the characteristic response of EXPOSURE and SPECTRUM OF EFFECTS of toxic agents Mostly CONSISTENT WITH THE DOSE OR AMOUNT OF TOXICANT INCREASES THE DOSE,= INCREASE THE RESPONSE or TOXIC EFFECT of one individual but sometime different response also will manifest to a population	Dose-Response Relationship
Dose-Response Two Types	1 Individual, or Graded Dose-Response Relationship 2 Quantal Dose-Response Relationship-Normal or Gaussian Distribution
§ characterized by a DOSE-RELATED INCREASE IN THE SEVERITY OF THE RESPONSE § As you INCREASE THE DOSE of the ORGANOPHOSPHATE the PERCENT INHIBITION also INCREASE. Therefore in this response there is DIRECTLY PROPORTIONAL relationship between the RESPONSE OF INHIBITION AND THE DOSE	Individual, or Graded Dose-Response Relationship
§ Population is classified as either a “responder” or a “nonresponder.” § LD50 - means you are trying to look on the 50% died on animal tested by giving a single dose of the substance then it is expected to death in 50% of the animal tested	Quantal Dose-Response Relationship-Normal or Gaussian Distribution
1 __ means ALL OR NONE 2 means you are trying to look on the 50% died on animal tested by giving a single dose of the substance then it is expected to death in 50% of the animal tested	1 QUANTAL 2 LD50
1 animals that RESPOND AT LOWER DOSE 2 Animals that DIED AT HIGHER DOSE	1 HYPERSUSCEPTIBLE 2 RESISTANT
2. Quantal Dose-Response Relationships: sigmoid dose-response curve 1) +-1 SD = __ population (%) 2) +-2 SD = __ population (%) 3) +-3 SD = __ population (%)	. 1) 68.3% 2) 96.5% 3) 99.7%
Non-nutritional toxic substances • U-shaped curve • May also impart beneficial or stimulatory effects at low doses but, at higher doses, they produce adverse effects. • EXAMPLE: For example, chronic alcohol consumption is well recognized to increase the risk of esophageal cancer, liver cancer, and cirrhosis of the liver at relatively high doses, and this response is dose related	Hormesis
RATIO of the DOSE REQUIRED TO PRODUCE TOXIC EFFECT and dose needed to ELICIT THE DESIRED THERAPEUTIC RESPONSE	Therapeutic Index = : TD50/ED50
1 The LARGER the ratio between the TD50 and ED50, the __ the RELATIVE SAFETY of the drug or tested substance	greater larger ratio td50 & ed50 = MORE SAFE
§ INDICATOR OF THE MAGNITUDE OF THE DIFFERENCE BETWEEN AS ESTIMATED EXPOSE DOSE TO A HUMAN POPULATION and the no observable adverse effect level that is determined in the experimental animals § BETWEEN 1% and 99% RESPONDER	Margins of safety = LD1/ED99
1 range of doses over which a chemical produces increasing response 2 - reflects the limit of the dose response relationship on the response axis to a certain chemical o Increasing the dose will increase the response however, D has the maximal efficacy	1 POTENCY 2 EFFICACY
Variations in Toxic Responses:	1 Selective Toxicity 2 Species Differences 3 Individual Differences in response
means that a CHEMICAL PRODUCES INJURY TO ONE KIND OF LIVING MATTER WITHOUT HARMING ANOTHER FORM OF LIFE eventhough the two may exist in intimate contact o For example BAYGON only insects are harmem	Selective Toxicity
o Experimental RESULT MAY DIFFER IN DIFFERENT SPECIES o Between man and animal Identifying the mechanistic basis or species di differences in response to chemicals establishes the relevance of animal data to human response EX. For example when tested in animals it developed TUMORS but when tested in humans no TUMORS was developed	Species Differences
o Due to GENETIC DIFFERENCES THAT HAS NO SIDE EFFECTS o GENETIC POLYMORPHISM o Idiosyncratic	Individual Differences in response