Drug toxicity Flashcards
What is drug toxicity?
A harmful effect of a drug also known as adverse drug
reactions
How are adverse drug reactions discovered?
-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
Provide a few examples of drugs that have been taken out of the market and the side effects that athey caused?
- Fenfluramine (Caused valvular heart disease)
- Dexfenfaramine (Caused valvular heart disease)
- Astemizole (Caused arrythmias)
- Bromfenac (Cuased liver failure)
What causes on target adverse effects?
- Dose too high
- Chronic activation or inhibition effects
What causes off target adverse effects?
-Incorrect receptor is activated or inhibited
How can warfarin acting on the intended tissue but on the wrong receptor cause haemorrhaging and or deep vein thrombosis?
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.
Atropine is not a non selective muscarinic blocker. TRUE OR FALSE?
FALSE
What effects does Atropine cause?
- Dilates pupils
- Increases heart rate
- Reduces salivation and other secretions
- Relaxes smooth muscles
- Produces excitatory effects on the CNS
What are the two types of side effects caused by the use of atropine for the treatment of increased intestinal motility?
- Mydriasis
- Cycloplegia
Mydriasis and Cycloplegia have therapeutic uses in opthalmology. TRUE OR FALSE?
TRUE
Why is atropine not used to treat acid peptic disease ?
It may cause damage to patients stomach
What is nephrotoxicity?
Toxicity in the kidneys
Give an example of a drug that causes nephrotoxicity? as an off target effect?
Aminoglycosides
What symptoms occurs when a patient has nephrotoxicity?
- Reduced GFR
- increased creatinineamia and blood urea
- renal failure
What is cardiotoxicity?
Damage to the heart muscle
Give examples of drusg that cause cardiotoxicity?
- Terfenadine (antihistamine)
- Grepafloxacin (antibiotic)
- Astemizole (antihistamine)
- Sertinole (neuropletic)
What does hERG stand for?
-Human ether a go go related gene
What occurs if hERG is activated?
-causes prolongation of electrical impulses regulating the heart beat which can lead to fatal arrythmias
What type of channel does hERG work in?
Potassium channel
What happens to the T wave when hERG is activated?
It is delayed
Give an example of a drug that is a non selective b anatgonist?
Propranolol
Why is Propranolol contraindicated in patients with asthma?
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
In terms of enantiomeric effects, which configuration S-thalidomide or R-thalidomide causes inhibition?
S-thalidomide causes inhibition
While R gives the sedative therapeutic effect
What type of cell membranes does Paracetamol bind irreversibly to causing Liver necrosis?
hepatic cell membranes
Paracetamol can cause hepatoxicity. TRUE OR FALSE?
TRUE
Drugs do not generate immune responses due to their small size. TRUE OR FALSE?
TRUE
What two types of drugs that cause the immune system to be generated?
-Peptides and proteins of non human origins
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?
TRUE
Penicillin is not covalently bound to albumin. TRUE OR FALSE?
FALSE
What is hapten?
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.
What happens to low molecular drugs when they are metabolized into their activated metabolite and provide an example for this?
They can act as a hapten and bind to the carrier
e.g Sulfamethoxazole
LMW drugs interacts with the receptors of the immune system and bind directly to T-cell receptors. TRUE OR FALSE?
TRUE
How are the diagnosis of allergic response aided?
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.
What events occur during type 1 hypersensitivity reaction?
- 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
What events occur during type 2 hypersensitivity reaction?
- 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
What events occur during type 3 hypersensitivity reaction?
- 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
What events occur during type 4 hypersensitivity reaction?
- 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
What is an anaphylactic reaction?
These are sudden, widespread and potentially severe life threatning allergic reactions
What is the time frame for anaphylactic reaction?
Almost all occur within 4 hrs, most occur within 1 hr of taking the drug
What are the symptoms associated with anaphylactic reaction and provide examples for ecah symptom?
-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)
What is the treatment for anaphylaxis for mild reaction?
- Adrenaline 0.3-0.5ml
- Oral antihistamine
What is the treatment for anaphylaxis for severe reaction (massive angiodema)?
- Diphenhydramine 50-100mg
- Long acting adrenaline
- Oral antihistamine should be given for the next 24hrs
What is the treatment for anaphylaxis for asthmatic reactions that do not respond to adrenaline?
- Start up with IV fluids
- Theophylline 5mg/kg IV
- Endotracheal intubations or tracheotomy with O2 administration
What is the treatment for anaphylaxis for severe reactions involving the cardiovascular system?
- fluid replacement/vassopressor drugs e.g dopamine and noradrenaline
What is hypotention caused by in CV system?
Hypovolemia
What is the treatment for anaphylaxis for cardica arrest?
- Immediate resuscitation
- Followed by diphenhydramine
How can prophylaxis of penicillin allergy be tested?
-by doing a skin test
What type of Ig is useful in the diagnosis of reactions for penicillin, enzymes and some vaccines?
-IgE mediated
If the patients has a hsitory of having severe explosive reactions, agent should be diluted to 100 fold for intial testing. TRUE OR FALSE?
True
What is idiosyncratic toxicity?
This is a rare toxicity that isn’t well understood and may reflect genetic variation between individuals.
idiosyncratic toxicity has no obvious mechanism. TRUE OR FALSE?
TRUE
List all the mecahnisms of drug toxicity?
- On target effects
- Off target effects (Homologous effect or enantiomeric effects)
- Toxic metabolites
- Immune response
- Idiosyncratic response
What are the different drug toxicity due to interactions/
- Drug-drug interactions
- Drug-food interactions
- Drug-disease interactions
Give examples of the different Drug-disease interactions
- Liver disease
- Renal disease
- Cardica disease
- Acute viral infection
- Hypothyroidism
- Hyperthyroidism
