Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
35 Cards in this Set
- Front
- Back
|
Adverse reactions can be categorised into two types - list them and briefly, the effects that can arise from them
|
Type A (pharmacological) - side effects (direct pharmacological effect) and toxic effects
Type B (Hypersensitivity) - Immune (IgE or T cell) mediated (allergic) or non-immune mediated |
|
|
The Dose-Dependency curve of Toxicity levels out at very high doses, how is this so?
|
Usually due to saturation of metabolic enzymes (no more toxification?), binding sites, receptors, transporter proteins, defense/repair enzymes
|
|
|
Describe a mechanism for detoxification of free radicals
|
- Hydrogen extraction from GSH, a-tocopherol, ascorbic acid
- Superoxide dismutase converts O2'- to HOOH -> water (via catalase and glutathione peroxidase |
|
|
Describe how sulphamethoxazole (SMX) can generate a hapten, leading to sulphonamide allergy.
|
Sulphamethoxazole (SMX) is metabolised by CYP2C9 to NitrosoSMX (reactive), which can form a hapten -> inflammation. Use GSH to detoxify.
Radicals can also be formed in this process, leading to DNA damage, lipid peroxidation etc. |
|
|
Neoantigen formation can occur due to co-stimulation via cytokines - what is a source of these?
|
Cytokine release via cell stress/death (possibly due to haptenization)
Viral/bacterial infection |
|
|
Frusemide and celecoxib are examples of non-antibiotic sulphonamides. If one has a sulfa allergy, but not to sulfa non-antibiotics, is it ok to prescribe these?
|
It is ok to prescribe after patient counselling, but could try a test dose in a monitored setting (very small risk of cross-reactivity)
|
|
|
What can we deduce when an LFT shows that one liver enzyme is highly elevated?
|
Nothing - none of the enzymes used in the test are perfectly specific to the liver so we'd need to see elevations in all of them to conclude that liver damage has occurred.
|
|
|
Describe the 4 mechanisms of hepatotoxicity.
|
1. Disruption of Ca balance -> diassembly of actin fibrils -> cell blebbing and lysis OR interruption of transport pumps
2. Reactive metabolites -> adducts -> migrate to membrane and form immune targets 3. Stimulation of apoptosis 4. Inhibition of mitochondrial function -> metabolism inhibited |
|
|
Which mechanism of hepatotoxicity is generally responsible for cholestasis?
|
Disruption of calcium homeostasis.
|
|
|
Describe the mechanism of Cyclosporin in nephrotoxicity.
|
Cyclosporin causes constriction of the afferent arteriole (pre-renal effect). This may be due to NA release, increase Ca++ influx, decreased PGE2 production.
|
|
|
What advice would you give to a patient taking aciclovir (Zovirax) in terms of preventing nephrotoxicity?
|
Acyclovir is relatively insoluble in urine and can progress to deposition of crystals in tubular lumen/parenchyma (obstructive uropathy). Advise them to drink plenty of fluid to prevent precipitation. (pH adjustment may also be possible)
|
|
|
How are aminoglycosides able to bind to phospholipids in the process of causing lysosomal rupture?
|
Aminoglycosides are polycationic, and therefore can electrostatically attach to the anionic membrane phospholipids (as well as being filtered in the glomerulus as fast as water).
|
|
|
Ketoprofen, fenofibrate and amiodarone: not similar pharmacologically, but all share a common structure - what is it and why does it lead to photosensitivity?
|
They all share a diaryl ketone structure, allowing them to absorb photons of energy (via aromatic and C=O groups).
|
|
|
Phototoxicity reactions are dependent on: amount of compound, level of activating radiation and quantity of other chromophores in the skin. Explain the last factor.
|
The quantity of other chromophores involve the amount of melanin in the skin that competes with the drug to absorb radiation. This is why people with darker skin are less susceptible to phototoxicity/sensitivity.
|
|
|
How do fluoroquinolones produce phototoxicity? (clue: COX activation)
|
UVA -> quinolone -> formation of reactive oxygen species -> activate protein kinase C + tyrosine kinase -> activate COX -> formation of PGs -> inflammation!
|
|
|
Conditions such as Stevens-Johnsons Syndrome occur via formation of FasL ligands (for the death receptor). What can we administer to stop this?
|
Use IV Immunoglobulins (IVIG) that bind to the Fas ligand. This prevents binding of ligand to death receptor, blocking the apoptotic process.
|
|
|
Teratology: Organogenesis occurs between days 18-60 of gestation, which is critical for drug use to cause malformations. What happens if drug use occurs before and after this time period?
|
Before leads to higher chance of termination, while afterwards leads to subtle biochemical abnormalities rather than malformations.
|
|
|
Describe the mechanism of 'oligohydramnios' in the foetus.
|
Taking NSAIDs during the third trimester of pregnancy can lead to this condition. Fetal renal blood flow is reduced, decreasing the amount of amniotic fluid produced by the kidneys. This loss of protective fluid leads to the fetal malformations seen due to the uterine wall pressures on the foetus.
|
|
|
'You only really see birth defects when the baby is born, right?' disprove this statement with an example of a defect that appears later down the track.
|
Using diethystilboestrol (DES) can lead to clear cell adenocarcinoma at ages up to 14 years.
|
|
|
A man comes into your pharmacy complaining of a sore leg, he mentions he tried an NSAID cream, but now it has flared up. Which NSAID would he have used if only: his exposed leg was affected, or just his foot.
|
If it affected his leg only, it may have been a photosensitising NSAID like ketoprofen. Otherwise it may have just been contact allergy (new socks perhaps) and was using a non-photosensitising NSAID.
|
|
|
Which three enzymes detect hepatocellular necrosis and which two detect cholestasis?
-ALT, AST, LDH, ALP, GGT |
Hepatocellular necrosis: ALT, AST, LDH
Cholestasis: ALP, GGT |
|
|
Cholestasis can cause hepatocyte apoptosis by a number of mechanisms. How does the liver respond to this and what can we administer to help treat liver injury?
|
The liver responds by down-regulating bile acid transporters (decreasing uptake) and increasing secretion of bile acids. You can administer ursodeoxycholic acid, which reduces mitochondrial permeability (reducing apoptosis).
|
|
|
It was believed that anti-epileptic drugs cause teratogenesis by forming toxic metabolites such as epoxides. Point out a possible limitation (think about the foetus' metabolism)
|
Epoxides formed by the mother may not be able reach the foetus due to high polarity and that the fetus lacks required CYP450 to generate epoxides.
|
|
|
Intra-renal effects fall into two categories: acute interstitial nephritis and acute tubular necrosis. Differentiate the two in terms of allergy and dose-dependency.
|
Acute interstitial nephritis occurs on an allergic basis in a non-dose dependent matter. Acute tubular necrosis is characterized by tubular injury in the absence of inflammation, plus a degree of dose-dependency.
|
|
|
What is the role of deltaNp53 in the regulation of p53 activity?
|
deltaNp53 is how the cell can regulate p53's actions. It lacks the transactivation domain, so it competes with p53 for DNA binding (but doesn't lead to the transactivation of genes)
|
|
|
What happens to retinoblastoma when DNA damage is detected?
|
When damage is detected, the phosphorylation of retinoblastoma (by Cdk4/CyclinD complex) is reduced, increasing the amount of retinoblastoma blocking the promoter regions - reducing progress to S phase of cell cycle (no replication)
|
|
|
When do cell cycle non-specific agents exert an effect and how does this determine our dose?
|
Cell cycle non-specific agents exert their effect throughout the whole cycle (effective against cells in resting phase). Give in large intermittent doses.
|
|
|
Which two drugs alter the function of topoisomerase II?
|
Doxorubicin (single + double strand breaks) and epidpodophyllotoxins (single strand breaks).
|
|
|
What is the mode of action of the anitimetabolite, 6-mercaptopurine?
|
6-mercaptopurine inhibits synthesis of GMP and AMP (purines) and can be incorporated into DNA (after conversion to Thio-dGTP) or RNA (via ThioGTP)
|
|
|
Our patient is ready to be given methotrexate intrathecally, as well as vincristine via another route. Why should we be extremely careful of this?
|
This is due to possible mixup, leading to vincristine being given intrathecally, where it can exert neurotoxicity (peripheral neuropathy)
|
|
|
Name the unique drug toxicities of:
cyclophosphamide doxorubicin bleomycin irinotecan vincristine |
cyclophosphamide: haemorrhagic cystitis - via accumulation in bladder
doxorubicin: cardiac toxicity - via radical formation (+ low catalase/detoxification) bleomycin: pulmonary toxicity irinotecan: myelosuppression and diarrhoea vincristine: neurotoxicity |
|
|
Our patient in our pharmacy has been taking an anthracycline (doxorubicin) and comes in, complaining of the presence of blood in their urine. What action should we take?
|
We need to counsel the patient in that doxorubicin can make a patient's urine appear red, and that they should not think that it is blood.
|
|
|
Name three of the four molecular mechanisms of multi-drug resistance
|
Low extracellular concentration
Low concentration at molecular target Altered molecular target Alteration of response after action on molecular target |
|
|
List the problems of the first two, and the advantages of the last strategy of reversing Pgp-mediated MDR:
1st - verapamil: competitive inhibition 2nd - valspodar: nonimmunosuppressive analogue of cyclosporine D 3rd - tariquidar: non-competitive inhibitor |
1st - verapamil: required high concentrations, leading to toxicity; also interactions via CYP inhibition
2nd - valspodar: disappointing results, unpredictable PK interactions 3rd - tariquidar: does not effect CYP3A4 at req. concentrations, prevents ATP-binding/hydrolysis |
|
|
Explain how cells can become resistant to 5-FU and topoisomerase II poisons (doxorubicin + epipodophyllotoxins)
|
5-fluorouracil: cells become resistant via thymidylate synthetase overexpression
topoisomerase II poisons: underexpression of tp II and overexpression of tp I |
