201 HI - Disease & Pharmacology

Question 1

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 1

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

Question 2

AE of Glucocorticoids (corticosteroids)

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 2

Iatrogenic Cushing syndrome

Question 3

Antiproliferative immunosuppressants

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 3

Azathioprine

• Activated to 6-mercaptopurine (6-MP)

AE: Bone marrow suppression

Question 4

Calcineurin inhibitors

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 4

Ciclosporin

• Inhibit calcineurin, which normally activates the transcription of interleukin-2

AE: Hyperlipidaemia, hypertension, gingival hyperplasia, renal dysfunction

Question 5

mTOR inhibitors

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 5

Sirolimus

AE: Myelosuppression

Question 6

TNF-α inhibitors

Immuno- suppressors, immuno-modulators and antibody treatments

Answer 6

Infliximab

AE: Latent TB and other serious infections may recur

Question 7

Antithrombotic drugs

Answer 7

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

Question 8

Thrombolytics/fibrinolytics

Antithrombotic drugs

Answer 8

Alteplase

• Enzymically activate plasminogen to give plasmin which digests fibrin and fibrinogen, lysing the clot.

AE: Bleeding

Question 9

Heparin, low-molecular-weight heparin

Antithrombotic drugs

Answer 9

Enoxaparin

• Binds to AT III → inhibits factor Xa

Question 10

Vitamin K antagonist

Antithrombotic drugs

Answer 10

Warfarin

• Inhibits the reduction of vitamin K and thus prevents the γ-carboxylation of the glutamate residues in factors II, VII, IX, and X

Question 11

AE of Direct Oral Anticoagulants (DOACs)

Antithrombotic drugs

Answer 11

Bleeding

Question 12

Haem iron vs non-haem iron

Answer 12

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+)

Question 13

Mechanisms of iron absorption

Answer 13

1. Duodenal cytochrome B reduces Fe3+ → Fe2+ (meat product not needed to be converted)
2. DMT1 transport Fe2+ into duodenal enterocyte
3. Ferroportin export iron from enterocyte when needed - Fe2+ released from ferritin stores into blood
4. Hephaestin converts Fe2+ → Fe3+ - binds to transferrin and transported to target tissues
5. Fe3+ stored in ferritin

Question 14

Where does iron absorption mainly occur?

Answer 14

Duodenum

Question 15

How is iron absorption regulated?

Answer 15

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

Question 16

4 main causes of iron deficiency anemia

Answer 16

↓ iron intake
↓ iron absorption
↑ demand
↑ loss

Question 17

Hepcidin levels ______ in iron deficiency

Answer 17

decrease

Question 18

Primary & secondary causes of iron overload

Answer 18

Primary:

• hereditary hemochromatosis
• iron poisoning

Secondary:

• blood transfusions
• iron loading anemias

Question 19

What causes megaloblastic macrocytic anaemia?

Answer 19

Vitamin B12 & B9 (folate) deficiency

Question 20

What is the most common type of anemia?

Answer 20

Iron deficiency

Question 21

Iron deficiency can cause _____ anemia

Answer 21

hypochromic microcytic

Question 22

How can iron status be assessed?

Answer 22

Functional iron
Transported iron
Serum iron

Question 23

Treatment of iron overload

Answer 23

Iron chelation

Question 24

Cytotoxic drugs target mechanisms by which?

Answer 24

Cells divide & grow and prevents cell from dividing

Question 25

3 main approaches to delivering dose-intense chemotherapy

Answer 25

Dose escalation: increasing dosage

Reduction of interval: reduce the time between cycles

Sequential dosing: single or combination drugs given sequentially

Question 26

What are the 3 phases of chemotherapy?

Answer 26

Induction
Consolidation
Maintenance

Question 27

Hematological malignancies (3)

Answer 27

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

Question 28

MOA of Vincristine (for Acute Lymphoblastic Leukemia)

Answer 28

Inhibits microtubule assembly - disrupts M-phase

Question 29

Chronic leukaemia

Answer 29

Lots of partially developed WBC over a long period of time

Question 30

Chronic Myeloid Leukaemia (CML) vs Chronic Lymphoblastic Leukaemia (CLL)

Answer 30

CML affects granulocytes - neutrophil, basophil, eosinophil
- cells divide too quickly

CLL affects lymphocytes
- cells don’t die as they should

Question 31

Why are chemotherapy drugs often used in combination?

Answer 31

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

Question 32

Sepsis

Answer 32

A life-threatening condition that arises when the body’s response to an infection injures its own tissues & organs

Question 33

Septicaemia

Answer 33

Septicaemia is when bacteria enter the bloodstream, and cause blood poisoning which triggers sepsis

Question 34

What is SIRS (Systemic inflammatory response syndrome)?

Answer 34

A non-specific clinical response with 2 or more objective signs of systemic inflammation

全身炎症反應綜合症

Question 35

What is sepsis in the setting of SIRS?

Answer 35

SIRS w a presumed or confirmed infectious process

Infection associated w organ injury distant from the site of infection

Question 36

Is it required to have a confirmed infection to confirm sepsis?

Answer 36

No

- only ~60% of confirmed cases are w confirmed infections

Question 37

Role of endothelium

Answer 37

Maintains homeostasis between coagulation & fibrinolysis

Question 38

How does septic shock occur?

Answer 38

Sepsis increases nitric oxide levels

→ leading to excessive vasodilation & refractory hypotension

Question 39

When to prescribe antibiotic for sepsis pt?

Answer 39

ASAP

• don’t wait for culture, use broad spectrum antibiotic
• re-evaluate choice of antibiotics after culture data available

Question 40

The “sepsis six” bundle

Answer 40

1. Give high flow oxygen
2. Start intravenous fluid resuscitation
3. Take blood cultures
4. Give intravenous antibiotics
5. Measure lactate and FBC
6. Monitor accurate hourly urine output

Question 41

What is the target of HIV?

Answer 41

CD4+ lymphocytes

- cluster of differentiation protein 4

Question 42

How many copies of RNA does each HIV virion contain?

Answer 42

2

Question 43

Opportunistic infections

Answer 43

An infection caused by a pathogen that does not normally produce disease in a healthy individual

Question 44

Threshold of CD4+ to worry about opportunistic infections

Answer 44

<200 cells/mm3

Question 45

Causative agent of Kaposi’s sarcoma

Answer 45

Human herpes virus 8

Question 46

Causative agent of non-Hodgkin’s lymphoma

Answer 46

Epstein-Barr virus