# Formulas & Things to Remember Flashcards

1
Q

Half-life pharm formula

A

T1/2 = (0.693 x Vd)/Clearance

2
Q

Steady state concentration formula

A

Steady state (IV) = in / out

Steady state Css = (Bioavailability x Dose) / (Dose interval x Clearance)

3
Q

Oral bioavailability formula

A

Bio = AUC oral / AUC IV

4
Q

Renal dose adjustment for FU (fraction unbound)

A

Renal dose adjustment for FU of 1
= CrCl of patient / CrCl normal

Renal dose adjustment for FU <1
= (1 - FU) + FU (CrCl of patient / CrCl normal)

5
Q

Theapeutic Index formula

A

Therapeutic Index = LD50 / ED50

ED50 = median effective dose i.e. 50% sample has effect
LD50 is the amount ingested that kills 50% of test sample

6
Q

Potency vs Efficacy

A

Potency = dose required to produce 50% of maximal effect
- i.e. if 2 drugs have same maximum effect but Drug A achieves at a lower dose it is more potent than drug B

Efficacy = maximum effect expected from drug

7
Q

HLA*B1502 drug interaction

A

Carbamazepine & SJS/TEN

8
Q

HLA*B5701 drug interaction(s)

A

Abacavir hypersensitivity

Flucloxacillin drug induced liver injury

9
Q

HLA*B5801 drug interaction

A

Allopurinol in Han Chinese populations - risk of SJS/TEN

10
Q

A

Volume of distribution the main factor

Loading dose = desired concentration x Vd

11
Q

Odds ratio

A

OR = odds of exposure in cases / odds of exposure in controls
i.e. ad / bc

12
Q

Describe the flow-volume curves for the following:

1. Normal
2. Fixed obstruction
3. Variable extra-thoracic obstruction
- Causes?
4. Variable intra-thoracic obstruction
- Causes?
5. Restrictive disease
A
1. Normal = upside down ice-cream cone
2. Fixed obstruction = flat top and bottom (pancake)
- causes: goitre, tracheal stenosis, masses
3. Variable extra-thoracic obstruction = flat inspiration (stingy upside down ice cream cone)
- causes: laryngomalacia, vocal cord palsy
- Inspiration sucks in the upper airways
4. Variable intra-thoracic obstruction = flat expiration
( stingy upright ice cream cone)
- causes: tracheal masses, tracheomalacia
- Expiration increases pleural pressure worsening obstruction
5. Restrictive = small, low volume but normal shape
13
Q

List causes of:

A

(150 - 5/4 x paCO2) - paO2
or 1.2 x pCO2

1. V/Q mismatch (PE, pneumonia, ARDS, APO)
2. Right to left shunt
3. Alveolar hypoventilation (interstitial lung disease)

1. Hypoventilation (e.g. COPD, NMD)
2. High altitude
14
Q

Which drugs affect renin/aldosterone ratio testing?

• False negative
• False positive
A

False negative - increase renin

• ACEi
• ARB
• Diuretics
• Dihydropine CCBs (amlodipine)
```False positive - decrease renin
ABCD suppresses
Alpha-methyldopa
Beta blockers
Clonidine
Diclofenace (NSAIDs)```
```Hold diuretics (incl. spironolactone 6 weeks)
Other interfering meds 2-4 weeks
Verapamil, prazosin and hydralazine are ok to use```
15
Q

Describe Amiodarone effects on the thyroid

A

o Amiodarone has multiple mechanisms of interfering with thyroid function
 All patients have a transient rise in TSH due to Wolff-Chaikoff effect (temporary increase in thyroid production due to iodine load)
o Hypothyroidism occurs due to interference with T4 synthesis and action (also interferes with peripheral conversion of T4 to T3
 Treated with cessation +/- thyroxine

Thyrotoxicosis occurs by 1. Iodine load (type 1) and 2. Thyroiditis (type 2)
 Can occur anytime after starting Amiodarone (idiosyncratic)
 Amiodarone contains large amounts of iodine (200mg more than usual daily intake)  enhanced thyroid hormone production (type 1)
• More commonly in patients with underlying multinodular goitre
• Jod-Basedow phenomenon

 Amiodarone has a direct toxic effect on the thyroid follicular cells  release of excess thyroid hormone (type 2)
 Often mixed mechanism – AIT 1 more common early (e.g. <3 months) and AIT more common overall
• AIT 2 responds rapidly whereas AIT 1 responds slowly
o Management
 1. Stop Amiodarone
 2. PTU/Carbimazole (target type 1) AND steroids (target type 2)
 3. Colestyramine if desperate (blocks enterohepatic iodine circulation)
 4. Surgery if no response
 Note: Iodine radio-ablation is not helpful

16
Q

Causes of falsely high and low HbA1c?

A

High HbA1c

• True hyperglycaemia
• Low red cell turnover
• Splenectomy
• Can occur in iron deficiency/B12/folate def anaemia
• Alcoholism

Low HbA1c

• High red cell turnover: haemolysis, chronic blood loss, chronic renal failure (variable)
• Blood transfusion
17
Q

Antibody associated with scleroderma renal crisis

A

Anti-RNA polymerase 3

18
Q

Antibodies for necrotising immune mediated myopathy

A

Anti-HMGCR

Anti-SRP

19
Q

Antibody for Inclusion body myositis

A

Anti-cN1A

20
Q

Antibodies for dermatomyositis

A
```ANA 80%
Anti-Mi2
Anti-IFIH1 (MDA-5) = amyopathic DM
Anti-Jo1 = anti-synthetase
TIF1-gamma = strong association with malignancy```
21
Q

Scleroderma antibodies

A

Anti-centromere = CREST/limited scleroderma (associated with pulmonary hypertension)
Anti-RNA polymerase 3 = renal crisis
Anti U1 RNP = (high sensitivity for MCTD) but associated with SSc with pulmonary hypertension
Anti-Scl-70 (antitopoisomerase-1) = diffuse scleroderma (esp. pulmonary fibrosis)

22
Q

New agents for breast cancer
List 3 new(ish) classes
1 novel conjugate drug

A
1. CDK4/6 inhibitors = cyclin dependent kinase 4/6 inhibitors
- Prevent cell cycle progression
- E.g. Palbociclib, Ribociclib
- Improve progression free survivial in HR positive, HER2 negative breast cancer
- Neutropenia very common but infectious complications rare
2. PI3 kinase inhibitors phosphoinositide-3-kinsae inhibitor
- Inhibit PI3/AKT/mTOR signalling pathway and tumour suppression
- Alpelsiib (alpha specific PIK3K inh)
- Survival benefit in HR positive, HER2 negative advanced breast cancer in combination with Fulvestrant
- SEs: rash, hyperglycaemia, nausea/vomiting
3. PARP inhibitors (poly-ADP-ribose polymerase) inhibitors
- Increase Ds DNA breaks (normally PARP repairs these breaks through the BRCA pathway) with resulting cancer cell death
- Useful for BRCA positive breast cancer

T-DM1/Trastuzumab-Emtasine = antiboddy-drug conjugate (Herceptin linked to cytotoxic agent DM-1)

• On binding, internalises DM1 with local chemo activity
• Not superior to standard 1st line Trastuzumab regimens - often used as 2nd line therapy
23
Q

PI3 kinase inhibitors

A

PI3 kinase inhibitors phosphoinositide-3-kinsae inhibitor

• Inhibit PI3/AKT/mTOR signalling pathway and tumour suppression
• Alpelsiib (alpha specific PIK3K inh)
• Survival benefit in HR positive, HER2 negative advanced breast cancer in combination with Fulvestrant
• SEs: rash, hyperglycaemia, nausea/vomiting
24
Q

PARP inhibitors

A

PARP inhibitors (poly-ADP-ribose polymerase) inhibitors

• Increase Ds DNA breaks (normally PARP repairs these breaks through the BRCA pathway) with resulting cancer cell death
• Useful for BRCA positive breast cancer
25
Q

CDK4/6 inhibitors

A

CDK4/6 inhibitors = cyclin dependent kinase 4/6 inhibitors

• Prevent cell cycle progression
• E.g. Palbociclib, Ribociclib
• Improve progression free survivial in HR positive, HER2 negative breast cancer
• Neutropenia very common but infectious complications rare
26
Q

Abiraterone

Enzalutimide

A

Androgen biosynthesis inhibitors/blockers
Metastatic castrate resistant prostate cancer

Abiraterone – blocks 17a-hydroxylase enzyme with reduced adrenal androgens
• Tends to increase ACTH and lower aldosterone (hypertension, hypokalaemia)

Enzalutimide – Androgen receptor antagonist with reduced AR translocation
• Hypertension, fatigue, cognitive impairment

27
Q

HCC treatment options

• Very Early stage 0
• Early stage A
• Intermediate stage B
• Advanced stage C
• Terminal stage D
A

Very early stage 0 = single <2cm, preserved liver function and ECOG 0

• Treatment = Resection or ablation if not a transplant candidate
• Transplant if elevated portal pressure or bilirubin

Early stage = solitary or up to 3 nodules <3cm
- Transplantation or ablation

Intermediate stage = multinodular, ECOG 0 & preserved liver function

• TACE/chemoemobilisation
• Survival usually >2-5 years

Advanced stage = portal invasion, extrahepatic spread, ECOG 1-2 (survival >1yr)

• Systemic therapy = Sorafenib (anti-Raf kinase, VEGFR) or Lenvatinib (multi VEGFR, FGFR)
• Hypertension associated with treatment benefit
• SEs: hypertension, renal dysfunction, hand-foot skin reaction, rash, poor wound healing

Terminal stage = end-stage liver function, ECOG 3-4 = best palliative care (survival 3 months)

28
Q

Absolute risk

A

Absolute risk = event rate / total in group

29
Q

Absolute risk reduction

A

ARR = CER - EER

30
Q

Relative risk

A

RR = EER / CER

31
Q

Relative risk reduction

A

RRR = (CER - EER) / CER

RRR = 1 - RR

32
Q

Power

A

Probability of rejecting the null hypothesis (correctly) when it is false

Power = 1 - type II error

Type 1 error = false positive
Type 2 error = false negative rate
i.e. it is like telling a heavily pregnant women she is not pregnant because the test came back negative

33
Q

Testicular cancer tumour markers

A

AFP = non-seminomatous (predmoninantly yolk sac, teratomas)
- Pure seminoma and pure choriocarcinoma do not produce AFP

```o	B-HCG = Choriocarcinoma, some embryonal cell and seminomas
o	LDH (low specificity)```
34
Q

In addition to cytotoxic T cells, which other immune cell is primarily dysfunctional in the
pathophysiology of haemophagocytic lymphohistiocytosis?
A. Dendritic.
B. Macrophage.
C. Mast.
D. Natural killer.
E. T helper.

A

Answer: D - natural killer cells

35
Q

Neuromyelitis optica antibody

Multifocal motor neuropathy antibodies

A

NMO = anti-Aquaporin-4 antibody
anti-MOG less common

MMN = anti-GM1

36
Q
```BCL-2 inhibitors have recently shown to have therapeutic efficacy in blood cancers.
What is the function of BCL-2 protein?
A. Activates cell death receptors.
B. Activates cell survival proteins.
C. Activates effector caspases.
D. Inhibits cell apoptotic proteins.
E. Inhibits cell survival proteins.```
A

Answer: D - Inhibits cell apoptotic proteins.

37
Q
```.If a patient has strong positive anti-dsDNA antibodies (> 100 IU/mL) and a negative screen for
extractable nuclear antigens (ENA), what is the most likely pattern on antinuclear antibody
(ANA) testing?
A. Centromere.
B. Homogeneous.
C. Negative (no pattern seen).
D. Nucleolar.
E. Speckled.```
A

Answer: B - homogenous

38
Q
```The pharmacokinetic properties of which analogue insulin are largely determined by binding to
and dissociation from serum albumin?
A. Aspart.
B. Detemir.
C. Glargine.
D. Glulisine.
E. Lispro.```
A

Answer: B - Detemir

39
Q

RTA type 1 vs 2 vs 4

A

 Proximal RTA (type 2) = HCO3 excretion defect
Fanconi syndrome: glycosuria, phosphaturia, uricaciduria, aminoaciduria
Myeloma/MGUS
Drugs: tenofovir, acetazolamide
pH < 5.5 (excess H+) – acidic

 Distal RTA (type 1) = H+ excretion defect
Causes Sjogren’s syndrome
SLE
Primary biliary cirrhosis, autoimmune hepatitis
Urine pH pH >5.5 (no H+) – alkaline

• Urine anion gap is helpful to differentiate normal AG metabolic acidosis (i.e. RTA1) vs diarrhoea
o Urinary AG = Na + K – CL
 Urine AG = positive in RTA type 1 (lack of H+  reduced NH4Cl)
 Urine AG = negative in diarrhoea (excess H+  increased NH4Cl)