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Ronnie's lectures > Drug toxicity > Flashcards

Drug toxicity Flashcards

1
Q

What is drug toxicity?

A

A harmful effect of a drug also known as adverse drug

reactions

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2
Q

How are adverse drug reactions discovered?

A

-through clinical trials
(Excluding the very young and old as well as pregnant women)
-Excludes patients with multiple diseases
-Excludes potentially other drug to drug interactions
-Once drug enters the market place

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3
Q

Provide a few examples of drugs that have been taken out of the market and the side effects that athey caused?

A
  • Fenfluramine (Caused valvular heart disease)
  • Dexfenfaramine (Caused valvular heart disease)
  • Astemizole (Caused arrythmias)
  • Bromfenac (Cuased liver failure)
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4
Q

What causes on target adverse effects?

A
  • Dose too high

- Chronic activation or inhibition effects

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5
Q

What causes off target adverse effects?

A

-Incorrect receptor is activated or inhibited

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6
Q

How can warfarin acting on the intended tissue but on the wrong receptor cause haemorrhaging and or deep vein thrombosis?

A

Warfarin prevents vitamin K reductase from converting oxidized vitamin K to reduced Vitamin K, this therefore prevents the formation of clotting factors, which if inhibited can also inhibit clot formation which would lead to haemorrhaging and possibly deep vein thrombosis.

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7
Q

Atropine is not a non selective muscarinic blocker. TRUE OR FALSE?

A

FALSE

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8
Q

What effects does Atropine cause?

A
  • Dilates pupils
  • Increases heart rate
  • Reduces salivation and other secretions
  • Relaxes smooth muscles
  • Produces excitatory effects on the CNS
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9
Q

What are the two types of side effects caused by the use of atropine for the treatment of increased intestinal motility?

A
  • Mydriasis

- Cycloplegia

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10
Q

Mydriasis and Cycloplegia have therapeutic uses in opthalmology. TRUE OR FALSE?

A

TRUE

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11
Q

Why is atropine not used to treat acid peptic disease ?

A

It may cause damage to patients stomach

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12
Q

What is nephrotoxicity?

A

Toxicity in the kidneys

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13
Q

Give an example of a drug that causes nephrotoxicity? as an off target effect?

A

Aminoglycosides

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14
Q

What symptoms occurs when a patient has nephrotoxicity?

A
  • Reduced GFR
  • increased creatinineamia and blood urea
  • renal failure
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15
Q

What is cardiotoxicity?

A

Damage to the heart muscle

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16
Q

Give examples of drusg that cause cardiotoxicity?

A
  • Terfenadine (antihistamine)
  • Grepafloxacin (antibiotic)
  • Astemizole (antihistamine)
  • Sertinole (neuropletic)
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17
Q

What does hERG stand for?

A

-Human ether a go go related gene

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18
Q

What occurs if hERG is activated?

A

-causes prolongation of electrical impulses regulating the heart beat which can lead to fatal arrythmias

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19
Q

What type of channel does hERG work in?

A

Potassium channel

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20
Q

What happens to the T wave when hERG is activated?

A

It is delayed

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21
Q

Give an example of a drug that is a non selective b anatgonist?

A

Propranolol

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22
Q

Why is Propranolol contraindicated in patients with asthma?

A

This is because drugs binding the b1 and b2 adrenergic recpetors are not selective to one subtype , so antagonsts binding the b2 adrenergic receptors will cancause airway constriction

23
Q

In terms of enantiomeric effects, which configuration S-thalidomide or R-thalidomide causes inhibition?

A

S-thalidomide causes inhibition

While R gives the sedative therapeutic effect

24
Q

What type of cell membranes does Paracetamol bind irreversibly to causing Liver necrosis?

A

hepatic cell membranes

25
Q

Paracetamol can cause hepatoxicity. TRUE OR FALSE?

A

TRUE

26
Q

Drugs do not generate immune responses due to their small size. TRUE OR FALSE?

A

TRUE

27
Q

What two types of drugs that cause the immune system to be generated?

A

-Peptides and proteins of non human origins

28
Q

Peptides and proteins of non human origins bind to low molecular weight drugs as a hapten on the macromolecular carrier causing the immune systme to be generated. TRUE OR FALSE?

A

TRUE

29
Q

Penicillin is not covalently bound to albumin. TRUE OR FALSE?

A

FALSE

30
Q

What is hapten?

A

It is a small molecule which when combined with a larger carrier such as a protein can elicit the production of antibodies; which bind specfically to it in the free or combined state.

31
Q

What happens to low molecular drugs when they are metabolized into their activated metabolite and provide an example for this?

A

They can act as a hapten and bind to the carrier

e.g Sulfamethoxazole

32
Q

LMW drugs interacts with the receptors of the immune system and bind directly to T-cell receptors. TRUE OR FALSE?

A

TRUE

33
Q

How are the diagnosis of allergic response aided?

A

They can be aided because different drugs evoke different types of reactions, so therefore can be used to determine what type of allergic reaction has occured.

34
Q

What events occur during type 1 hypersensitivity reaction?

A
  • Hapten bind to protein 1 e.g penicillin
  • Antigen cross links IgE antibodies on the surface of mast cell, leading to mast cell degranulation
  • Mast cell relases histamine and other inflammatory mediators
35
Q

What events occur during type 2 hypersensitivity reaction?

A
  • Antigen binds to the surface of a circulating blood cell, usually a red blood cell
  • Antibodies to the antigen then bind the surface of the RBC attracting cytotoxic T cells
  • Which releases mediators that lyse the RBC
  • Binding of antibody to RBCs can also directly stimulate complement mediated RBC lysis and RBC removal by the reticuloendothelial system
36
Q

What events occur during type 3 hypersensitivity reaction?

A
  • Antibodies bind to a soluble toxin acting as an antigen
  • The antigen-antibody complexes are then deposited in the tissues attracting macrophages
  • Which starts a complement mediated reaction sequence
37
Q

What events occur during type 4 hypersensitivity reaction?

A
  • Hapten bind to a protein
  • The hapten bound protein is phagocytosed by a langerhans cell
  • The langerhans cell migrate to regional lymph node, where it presents an antigen to a T cell, thereby activating T cell
38
Q

What is an anaphylactic reaction?

A

These are sudden, widespread and potentially severe life threatning allergic reactions

39
Q

What is the time frame for anaphylactic reaction?

A

Almost all occur within 4 hrs, most occur within 1 hr of taking the drug

40
Q

What are the symptoms associated with anaphylactic reaction and provide examples for ecah symptom?

A 
-Skin reactions 
(hives, redness, itching)
-Difficult breathing 
(Chest tightness, wheezing)
-Fainting 
(light headness, loss of consciousness due to drastic drop in BP, irregular haert beat)
-Swelling
 (of face, tongue, lips and throat)
41
Q

What is the treatment for anaphylaxis for mild reaction?

A
  • Adrenaline 0.3-0.5ml

- Oral antihistamine

42
Q

What is the treatment for anaphylaxis for severe reaction (massive angiodema)?

A
  • Diphenhydramine 50-100mg
  • Long acting adrenaline
  • Oral antihistamine should be given for the next 24hrs
43
Q

What is the treatment for anaphylaxis for asthmatic reactions that do not respond to adrenaline?

A
  • Start up with IV fluids
  • Theophylline 5mg/kg IV
  • Endotracheal intubations or tracheotomy with O2 administration
44
Q

What is the treatment for anaphylaxis for severe reactions involving the cardiovascular system?

A
  • fluid replacement/vassopressor drugs e.g dopamine and noradrenaline
45
Q

What is hypotention caused by in CV system?

A

Hypovolemia

46
Q

What is the treatment for anaphylaxis for cardica arrest?

A
  • Immediate resuscitation

- Followed by diphenhydramine

47
Q

How can prophylaxis of penicillin allergy be tested?

A

-by doing a skin test

48
Q

What type of Ig is useful in the diagnosis of reactions for penicillin, enzymes and some vaccines?

A

-IgE mediated

49
Q

If the patients has a hsitory of having severe explosive reactions, agent should be diluted to 100 fold for intial testing. TRUE OR FALSE?

A

True

50
Q

What is idiosyncratic toxicity?

A

This is a rare toxicity that isn’t well understood and may reflect genetic variation between individuals.

51
Q

idiosyncratic toxicity has no obvious mechanism. TRUE OR FALSE?

A

TRUE

52
Q

List all the mecahnisms of drug toxicity?

A
  • On target effects
  • Off target effects (Homologous effect or enantiomeric effects)
  • Toxic metabolites
  • Immune response
  • Idiosyncratic response
53
Q

What are the different drug toxicity due to interactions/

A
  • Drug-drug interactions
  • Drug-food interactions
  • Drug-disease interactions
54
Q

Give examples of the different Drug-disease interactions

A
  • Liver disease
  • Renal disease
  • Cardica disease
  • Acute viral infection
  • Hypothyroidism
  • Hyperthyroidism

Ronnie's lectures (12 decks)

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