81. Cytotoxic And Embryotoxic Effects Of Drugs. Drug Allergy

Front 1

Name some examples of side effects of drugs

Back 1

- Drysness of mouth with atropine- Sedation by first-gen H1 antagonists- Constipation with morphine or anti-tussives- GI symptoms with almost every drug (atleast antibiotics)

Front 2

What is an adverse drug reaction?

Back 2

An unwanted, possibly harm-causing reaction occuring when taking the drug normally. It can be related to its main pharmacological effect or unrelated to it.

Front 3

Name some examples of adverse effects related to the drugs main pharmacological effect. Are they dose-dependent?

Back 3

- Postural hypotension with a1 antagonists- Bleeding with anticoagulants and antiplatelets- Sedation by anxiolytics (benzodiazepines)
They are dose-dependent and can be prevented by decresing the dose.

Front 4

Name some examples of adverse effects not related to the drugs main pharmacological effect. Is it dose dependent?

Back 4

- Hepatotoxicity with paracetamol- Aplastic anemia from chloramphenicol- Anaphylaxis from penicillins- Halothane hepatitis
They are often unpredictable and not dose-dependent, also called idiosyncratic/type B reactions. They are often also irreversible

Front 5

What causes the adverse effects of a drug which is unrelated to its pharmacological effect?

Back 5

Reactive metabolites or immunological reactions

Front 6

How can overdosing happen?

Back 6

Increasing consumption or decreased excretion, like in kidney or liver failure.

Front 7

Name some examples of overdosage

Back 7

- Hepatotoxicity with paracetamol- Coma, barbiturates- Heart block, digoxin- Bleeding with anticoagulants and antiplatelets

Front 8

How can reactive metabolites cause damage? Name an example

Back 8

They can directly cause cellular damage by producing reactive oxygen species which oxidize RNA, DNA, lipids and proteins. This can lead to cell death.
They can also bind to glutathione, reducing the pool of GSH and reducing the cells defence against oxidative stress.
A common example is paracetamol metabolized into NAPQI.

Front 9

Name examples of drugs causing hepatotoxicity

Back 9

- Paracetamol- Isoniazid- Halothane- Chlorpromanzine- Amoxicillin-clavulanate (most cases!)

Front 10

Which different forms of kidney injury can drugs cause?

Back 10

- Acute renal failure- Interstitial nephritis- Chronic kidney disease- Analgesic nephropathy- Variable kidney injury

Front 11

Examples of drugs causing acute renal failure?

Back 11

- NSAIDs- ACEIs

Front 12

Examples of drugs causing interstitial nephritis?

Back 12

NSAIDs

Front 13

Examples of drugs causing chronic kidney disease?

Back 13

- Aminoglycosides- Antivirals- Lithium

Front 14

Examples of drugs causing analgesic nephropathy?

Back 14

- Aspirin- NSAIDs- Paracetamol

Front 15

Drugs causing varible kidney injury?

Back 15

- Cyclosporin- Amphotericin B- Cisplatin- Beta-lactams

Front 16

How do NSAIDs and aspirin cause kidney damage?

Back 16

They inhibit COX, which reduces the production of prostaglandins. This causes the blood flow to the kidney to decrease, affecting the most vulnerable parts to ischemia, renal papillae.

Front 17

How do ACEIs cause acute renal failure?

Back 17

Angiotensin II is nephroprotective since it keeps GFR at normal levels even when there is low renal blood flow. ACEIs reduce the amount of angiotensin 2 and there is no longer protection.

Front 18

What is the definition of mutagenesis?

Back 18

Induction of mutations in DNA by drugs. Can cause cancer if the cell does not die from the mutations.

Front 19

Definition of carcinogenic?

Back 19

Carcinogenic drugs can be genotoxic or erpigenetic.
Genotoxic cause mutations diretcly after being converted into reactive metabolites.
Epigenetic increase the possibility that a mutagen will cause cancer but are not mutagenic themselves.

Front 20

What is the Ames test?

Back 20

Test used to see if a chemical is mutagenic. Can be tested by giving the drug to salmonella who cant produce histidine itself. If the bacteria is growing, the drug is mutagenic since it got mutations for producing histidine.
Rat liver is used to see if the drug metabolite is mutagenic.

Front 21

Definition of teratogenesis?

Back 21

Major anomalies of the embryo due to exposure to teratogens during organogenesis in week 3-8

Front 22

Definition of embryopathy?

Back 22

Minor anomalies in the fetus by some drugs taken in week 9 until birth.

Front 23

What can happen if the embryo is exposed to teratogenic drugs in week 1-3?

Back 23

It can kill the embryo by inhibiting cell division, or the embryo can survive without any anomalies (except for alcohol)

Front 24

Mechanism of teratogenesis?

Back 24

Damage to DNA and interfering with morphogenesis.
Methotrexate and phenytoin inhibit folate synthesis for example.

Front 25

Give some examples of important teratogens and the deformities they cause

Back 25

- Thalidomide - No development of the long bones of the extremeties, resulting in seal arms.
- Alkylating agents, antimetabolites, folate antagonists (cytotoxic drugs) - Abortion or other malformations
- Retinoids - skeletal deforminites
- Phenytoin - cleft palate
- Valproate - neural tube defects
- Warfarin - saddle nose, retardation, CNS abnormalities
- Ethanol - Fetal alcohol syndrome

Front 26

Which antibiotic is first choice in pregnancy?

Back 26

Penicillins.

Front 27

Which antibiotics are contraindicated in pregnancy?

Back 27

- Tetracyclines- Aminoglycosides- Chloramphenicol- Sulphonamides- Trimethoprim- Linezolid

Front 28

"Which ""main rules"" do drug allergies usually follow?"

Back 28

- They occur a few days after drug use, or after repeated use.- Allergic reactions may occur in small doses, even so small there is no pharmacodynamic effect- Results in a clinical syndrome assosiated with type I, II, III or IV hypersensitivity- The allergy is unrelated to the main effects of the drug.

Front 29

Which drugs cause type I hypersensivity reactions? What are the symptoms?

Back 29

- Penicillin- Streptokinase- Heparin- Radiological contrast material- Vaccines
Can cause urticaria, hypotension and anaphylaxis etc.

Front 30

Mechanism of type II hypersensitivity reaction to drugs?

Back 30

The drugs may act as haptens when they bind to endogenous proteins. This leads to eg. hemolysis of RBCs or cytopenias.

Front 31

Which drugs cause hemolytic anemia?

Back 31

- Sulphoamides- Methyldopa

Front 32

Which drugs cause agranulocytosis?

Back 32

- NSAIDs (phenylbutazone)- Carbimazole- Clozapine- Suphonamides

Front 33

Which drugs can cause thrombocytopenia?

Back 33

- Quinine- Heparin- Thiazides

Front 34

Which drug can cause aplastic anemia?

Back 34

Chloramphenicol. This is irreversible

Front 35

How does halothane cause hepatitis?

Back 35

The reactive metabolite of halothane acts as a hapten. It binds to proteins found on hepatocytes, making them immunogenic. Antibodies will recognize them and immune cells will kill them.

Front 36

Which drugs can cause type III hypersensitivity reaction?

Back 36

HydralazineProcainamide
Not on the market anymore.

Front 37

Which drugs can cause type IV hypersensitivity and what can it lead to?

Back 37

- Allopurinol- Antiepileptics like carbamazepine, lamotrigine, phenytoin- Suphonamides
Can lead to Stevens-Johnson syndrome or toxic epidermal necrolysis