Pharmacotoxicity

Question 1

Pharmacotoxicology

Answer 1

part of pharmacology that studies the side effects of drugs

Question 2

Adverse reactions

Answer 2

undesirable effects that occur at doses commonly used in therapy

Question 3

Acute intoxication

Answer 3

Harmful manifestations that occur at very high doses , exceeding those used in therapy

Question 4

Predictable adverse reactions from non - clinical pharmacology data / previous clinical trials are called

Answer 4

Adverse reactions - may occur during clinical trials prior to authorization of the medical product , but unexpected adverse reactions may also occur

Question 5

Toxic side effects

Answer 5

• dose depedent reactions
• more frequent + severe in high doses
• these side effects can be detected before the introduction of drug into therapy - some even in the non - clinical research phase

Question 6

LD50

Answer 6

A parameter that determines the toxicity of a substance

- the lower the LD50 -> the more toxic the substance is

Question 7

ED50

Answer 7

the dose that is effective in 50 % of subjects / produces half of the max effect

Question 8

therapeutic index

Answer 8

is the ratio between LD50 and ED50

Question 9

When we can not determine LD50 we use

Answer 9

LD1 ( Minimum lethal dose 1 )

MTD maximun tolerated dose = max dose that could be administered and did not kill any lab animal

Question 10

for the determination of safety of drug is important to determine

Answer 10

chronic toxicity after repeated doses

Question 11

Mechanisms of toxic effect

Answer 11

1 ) Exaggeration of therapeutic effect : following the same mech + on same receptors as in the case of the therapeutic effect , recs located right in organ whose disease is being treated
2) Acting on the same pharmacological recs as in the case of the therapeutic effect , but these are recs located in organs other than those whose condition is being treated
3 ) through mechanism other than the one through which the therapeutic effect occur
4 ) people more sensitive to drugs , who have toxic phenomena at high therapeutic doses / increased sensitivity of certain organ
5) Pharmacokinetic problems : increase in plasma levels of the drug , sometimes we encounter phenomena of prevention of elimination of the dtug -> administration of this drug lead to -> increase serum level of the drug + toxicity
6 ) Increase in concentration of the free form of the drug , unrelated to plasma proteins

Question 12

Pharmacokinetic problems

Answer 12

• inrcrease plasma levels

- sometimes -> phenomena as prevention of elimination of a drug from the body

Question 13

Idiosyncratic side effects

Answer 13

• occur at low doses , but only in certain
  people who have an increased sensitivity (responsiveness) to certain substances.
  This sensitivity is usually genetically determined. Depending on the genetic deficiency, these side effects may occur as a drug intoxication, even though low doses have been given, or may occur completely differently from the usual effects of the drug.
  Those that manifest as intoxication are usually due to a genetic deficiency in the enzyme that is involved in the metabolism of the drug.

Question 14

glucose-6-phosphate dehydrogenase deficiency

Answer 14

enzyme involved in maintaining the shape of the red blood cell. In such people many drugs can cause hemolytic anemia

Question 15

Allergic side effects

Answer 15

are harmful effects due to the intervention of immune
mechanisms. They occur at very low doses of the drug, if the person has been previously sensitized to that drug. These reactions involve an antigen-antibody immune mechanism.

Question 16

drug allergies - type I, or anaphylactic,

mechanism

Answer 16

involves the formation of immunoglobulin E-type

antibodies.

Question 17

type II or cytotoxic mechanism

Answer 17

drug binds to certain proteins on the cell
surface, modifies them structurally and turns them into antigens. This results in the synthesis of immunoglobulin G-type antibodies directed against the respective cells

Question 18

type III mechanism

Answer 18

involves the formation of circulating antigen

(drug) -antibody immune complexes, which are deposited in small vessels in the kidneys, joints, etc.

Question 19

a type IV mechanism

Answer 19

consists in sensitizing
T-type lymphocytes, producing delayed-type adverse reactions. The manifestations are usually cutaneous, the most characteristic being the contact dermatitis, caused for example by antibiotics with local application such as neomycin, gentamicin and others.