201 HI - Disease & Pharmacology Flashcards
Immuno- suppressors, immuno-modulators and antibody treatments
Induction therapy for transplantation
- Lymphocyte-depleting agents - Antithymocyte globulin
- Interleukin 2 receptor antagonists - Basiliximab
Glucocorticoids (corticosteroids)
Antiproliferative immunosuppressants - Azathioprine
Calcineurin inhibitors - Ciclosporin
mTOR inhibitors - Sirolimus
TNF-α inhibitors - Infliximab
Antibodies against CD20 - Rituximab
Interleukin inhibitors - Tocilizumab
Janus kinase (JAK) Inhibitors - Tofacitinib Immunomodulation therapy - Interferons, interleukins, IVIG
AE of Glucocorticoids (corticosteroids)
Immuno- suppressors, immuno-modulators and antibody treatments
Iatrogenic Cushing syndrome
Antiproliferative immunosuppressants
Immuno- suppressors, immuno-modulators and antibody treatments
Azathioprine
- Activated to 6-mercaptopurine (6-MP)
AE: Bone marrow suppression
Calcineurin inhibitors
Immuno- suppressors, immuno-modulators and antibody treatments
Ciclosporin
- Inhibit calcineurin, which normally activates the transcription of interleukin-2
AE: Hyperlipidaemia, hypertension, gingival hyperplasia, renal dysfunction
mTOR inhibitors
Immuno- suppressors, immuno-modulators and antibody treatments
Sirolimus
AE: Myelosuppression
TNF-α inhibitors
Immuno- suppressors, immuno-modulators and antibody treatments
Infliximab
AE: Latent TB and other serious infections may recur
Antithrombotic drugs
Thrombolytics/fibrinolytics - Alteplase
Heparin - Enoxaparin
Low-molecular-weight heparin - Fondaparinux
Direct thrombin inhibitor - Bivalirudin
Vitamin K antagonist - Warfarin
Direct Oral Anticoagulants (DOACs) - Dabigatran
Antiplatelet drugs:
- Aspirin
- P2Y12 antagonists - Clopidogrel (CYP2C19)
- GPIIb/IIIa Receptor Antagonists - Abciximab
Thrombolytics/fibrinolytics
Antithrombotic drugs
Alteplase
- Enzymically activate plasminogen to give plasmin which digests fibrin and fibrinogen, lysing the clot.
AE: Bleeding
Heparin, low-molecular-weight heparin
Antithrombotic drugs
Enoxaparin
- Binds to AT III → inhibits factor Xa
Vitamin K antagonist
Antithrombotic drugs
Warfarin
- Inhibits the reduction of vitamin K and thus prevents the γ-carboxylation of the glutamate residues in factors II, VII, IX, and X
AE of Direct Oral Anticoagulants (DOACs)
Antithrombotic drugs
Bleeding
Haem iron vs non-haem iron
Haem:
- binds to haemoglobin & myoglobin
- can be found in animal products
- in ferrous state (Fe2+)
Non-Haem:
- free iron molecules
- can be found in plant-based foods
- in ferric state (Fe3+)
Mechanisms of iron absorption
- Duodenal cytochrome B reduces Fe3+ → Fe2+ (meat product not needed to be converted)
- DMT1 transport Fe2+ into duodenal enterocyte
- Ferroportin export iron from enterocyte when needed - Fe2+ released from ferritin stores into blood
- Hephaestin converts Fe2+ → Fe3+ - binds to transferrin and transported to target tissues
- Fe3+ stored in ferritin
Where does iron absorption mainly occur?
Duodenum
How is iron absorption regulated?
Hepcidin
- produced in the liver in response to increased iron load & inflammation
- binds to ferroportin and causes degradation
High hepcidin levels block intestinal iron absorption
4 main causes of iron deficiency anemia
↓ iron intake
↓ iron absorption
↑ demand
↑ loss
Hepcidin levels ______ in iron deficiency
decrease
Primary & secondary causes of iron overload
Primary:
- hereditary hemochromatosis
- iron poisoning
Secondary:
- blood transfusions
- iron loading anemias
What causes megaloblastic macrocytic anaemia?
Vitamin B12 & B9 (folate) deficiency
What is the most common type of anemia?
Iron deficiency
Iron deficiency can cause _____ anemia
hypochromic microcytic
How can iron status be assessed?
Functional iron
Transported iron
Serum iron
Treatment of iron overload
Iron chelation
Cytotoxic drugs target mechanisms by which?
Cells divide & grow and prevents cell from dividing
3 main approaches to delivering dose-intense chemotherapy
Dose escalation: increasing dosage
Reduction of interval: reduce the time between cycles
Sequential dosing: single or combination drugs given sequentially
What are the 3 phases of chemotherapy?
Induction
Consolidation
Maintenance
Hematological malignancies (3)
Leukaemia - cancer which starts usually in bone marrow 白血病
Lymphoma - cancer that begins in lymphocytes 淋巴瘤
Myeloma - cancer that forms in plasma cells 骨髓瘤
MOA of Vincristine (for Acute Lymphoblastic Leukemia)
Inhibits microtubule assembly - disrupts M-phase
Chronic leukaemia
Lots of partially developed WBC over a long period of time
Chronic Myeloid Leukaemia (CML) vs Chronic Lymphoblastic Leukaemia (CLL)
CML affects granulocytes - neutrophil, basophil, eosinophil
- cells divide too quickly
CLL affects lymphocytes
- cells don’t die as they should
Why are chemotherapy drugs often used in combination?
To provide maximum cell kill within the range of toxicity
To broaden the range of interaction between drugs & tumor cells
To prevent or slow the development of cellular drug resistance
Sepsis
A life-threatening condition that arises when the body’s response to an infection injures its own tissues & organs
Septicaemia
Septicaemia is when bacteria enter the bloodstream, and cause blood poisoning which triggers sepsis
What is SIRS (Systemic inflammatory response syndrome)?
A non-specific clinical response with 2 or more objective signs of systemic inflammation
全身炎症反應綜合症
What is sepsis in the setting of SIRS?
SIRS w a presumed or confirmed infectious process
Infection associated w organ injury distant from the site of infection
Is it required to have a confirmed infection to confirm sepsis?
No
- only ~60% of confirmed cases are w confirmed infections
Role of endothelium
Maintains homeostasis between coagulation & fibrinolysis
How does septic shock occur?
Sepsis increases nitric oxide levels
→ leading to excessive vasodilation & refractory hypotension
When to prescribe antibiotic for sepsis pt?
ASAP
- don’t wait for culture, use broad spectrum antibiotic
- re-evaluate choice of antibiotics after culture data available
The “sepsis six” bundle
- Give high flow oxygen
- Start intravenous fluid resuscitation
- Take blood cultures
- Give intravenous antibiotics
- Measure lactate and FBC
- Monitor accurate hourly urine output
What is the target of HIV?
CD4+ lymphocytes
- cluster of differentiation protein 4
How many copies of RNA does each HIV virion contain?
2
Opportunistic infections
An infection caused by a pathogen that does not normally produce disease in a healthy individual
Threshold of CD4+ to worry about opportunistic infections
<200 cells/mm3
Causative agent of Kaposi’s sarcoma
Human herpes virus 8
Causative agent of non-Hodgkin’s lymphoma
Epstein-Barr virus
