Formulas & Things to Remember Flashcards
Half-life pharm formula
T1/2 = (0.693 x Vd)/Clearance
Steady state concentration formula
Steady state (IV) = in / out
Steady state Css = (Bioavailability x Dose) / (Dose interval x Clearance)
Oral bioavailability formula
Bio = AUC oral / AUC IV
Renal dose adjustment for FU (fraction unbound)
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)
Theapeutic Index formula
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
Potency vs Efficacy
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
HLA*B1502 drug interaction
Carbamazepine & SJS/TEN
HLA*B5701 drug interaction(s)
Abacavir hypersensitivity
Flucloxacillin drug induced liver injury
HLA*B5801 drug interaction
Allopurinol in Han Chinese populations - risk of SJS/TEN
Loading dose determinant
Volume of distribution the main factor
Loading dose = desired concentration x Vd
Odds ratio
OR = odds of exposure in cases / odds of exposure in controls
i.e. ad / bc
Describe the flow-volume curves for the following:
- Normal
- Fixed obstruction
- Variable extra-thoracic obstruction
- Causes? - Variable intra-thoracic obstruction
- Causes? - Restrictive disease
- Normal = upside down ice-cream cone
- Fixed obstruction = flat top and bottom (pancake)
- causes: goitre, tracheal stenosis, masses - Variable extra-thoracic obstruction = flat inspiration (stingy upside down ice cream cone)
- causes: laryngomalacia, vocal cord palsy
- Inspiration sucks in the upper airways - Variable intra-thoracic obstruction = flat expiration
( stingy upright ice cream cone)
- causes: tracheal masses, tracheomalacia
- Expiration increases pleural pressure worsening obstruction - Restrictive = small, low volume but normal shape
A-a gradient formula
List causes of:
Elevated gradient
Low gradient
(150 - 5/4 x paCO2) - paO2
or 1.2 x pCO2
High A-a gradient:
- V/Q mismatch (PE, pneumonia, ARDS, APO)
- Right to left shunt
- Alveolar hypoventilation (interstitial lung disease)
Low/normal A-a gradient:
- Hypoventilation (e.g. COPD, NMD)
- High altitude
Which drugs affect renin/aldosterone ratio testing?
- False negative
- False positive
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
Describe Amiodarone effects on the thyroid
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
Causes of falsely high and low HbA1c?
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
Antibody associated with scleroderma renal crisis
Anti-RNA polymerase 3
Antibodies for necrotising immune mediated myopathy
Anti-HMGCR
Anti-SRP
Antibody for Inclusion body myositis
Anti-cN1A
Antibodies for dermatomyositis
ANA 80% Anti-Mi2 Anti-IFIH1 (MDA-5) = amyopathic DM Anti-Jo1 = anti-synthetase TIF1-gamma = strong association with malignancy
Scleroderma antibodies
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)
New agents for breast cancer
List 3 new(ish) classes
1 novel conjugate drug
- 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 - 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 - 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
PI3 kinase inhibitors
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
PARP inhibitors
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
CDK4/6 inhibitors
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
Abiraterone
Enzalutimide
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
HCC treatment options
- Very Early stage 0
- Early stage A
- Intermediate stage B
- Advanced stage C
- Terminal stage D
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)
Absolute risk
Absolute risk = event rate / total in group
Absolute risk reduction
ARR = CER - EER
Relative risk
RR = EER / CER
Relative risk reduction
RRR = (CER - EER) / CER
RRR = 1 - RR
Power
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
Testicular cancer tumour markers
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)
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.
Answer: D - natural killer cells
Neuromyelitis optica antibody
Multifocal motor neuropathy antibodies
NMO = anti-Aquaporin-4 antibody
anti-MOG less common
MMN = anti-GM1
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.
Answer: D - Inhibits cell apoptotic proteins.
.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.
Answer: B - homogenous
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.
Answer: B - Detemir
RTA type 1 vs 2 vs 4
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)
