College Learning Series Flashcards
Osteoporosis.
- Bisphosphonates. PO route GI intolerance, ONJ > IV. Renal impairment. Need drug holidays to prevent atypical #s.
- Denosumab. Rapid offset. Safe in renal disease.
- PTH analogues (teriparatide).
- Romosozumab (anabolic agent + osteoclast inhibition by blocking sclerostin). Followed by BP is better than BP alone.
Immunosuppressants and infection.
TNF-a: TB reactivation (infliximab, adalimumab)
CD20: HBV reactivation (rituximab)
Integrins: natalizumab pml
Steroids
IL-6 : tocilizumab, bacterial infections but better than adalimumab and doesn’t need to be used with methotrexate.
Opioids immunosuppressive.
Prevention: skin check (pyoderma or scabies), resp health, vaccination (flu, hep b, zoster but live vaccines not effective on immunosuppression so aim to wait 1 year, 2x doses shingrex valid 10 years), targeted testing pre-tx (hep b/c, Tb, HIV), IBD (c.diff)
Australian risk prediction : lymphopenia, disease activity, comorbidity burden, prior severe infection, age.
Valacyclovir to suppress zoster infection.
SGLT2 inhibitors.
Inhibit SGLT2 in PCT to decrease glomerular pressure, decrease GFR.
Landmark trials-
- DAPA-CKD and EMPA-Kidney: (1) T2DM + CKD + eGFR >30 = SGLT2i (2) T2DM + albuminuric CKD = SGLT2i, despite baseline HbA1c / target / metformin use.
(3) Dapagliflozin reduces risk of kidney failure in IgAN.
MECHANISM OF PROTECTION.
1. Activation of TGF
2. Natriuresis and BP lowering
3. Albuminuria lowering
4. Glucose control (HbA1c, with normal kidney function)
5. Weight loss
6. Inhibit cellular Na/H exchange
7. Restoration of normal autophagy
8. Efficiency energy utilization
9. Improvement in CV/Kidney oxygenation
10. Reduction in SNS activation
SGLT2i safely reduce risk of kidney failure requiring dialysis, CVD morbidity and mortality in people with proteinuric CKD +/- T2DM.
Ease of use-
- PO OD dosing
- no dose titration
- no drug-drug interactions
- no hyperkalaemia
- no AKI
Acute eGFR dip.
Glucose lowering therapy adjustment not needed.
Risk of volume depletion low, reduction in loop diuretic dose in euvolemic pts with normal BP considered.
Increased risk mycotic genital infections, mild and less issue without diabetes.
Practical tips.
- withhold tx pre-/ post-op to minimise risk of ketoacidosis with surgery
- withhold if unable to tolerate PO intake when ill
Urological cancers
- Prostate ca
- Renal ca
- Bladder ca
- Testicular ca
Prostate ca.
- castrate sensitive, castrate resistant.
- androgen deprivation therapy.
- GnRH agonists (goserelin) < antagonists (degarelix, rapid reduction with no initial flare).
- improved survival with early docetaxel (sensorimotor neuropathy and neutropenic sepsis)/carbazitaxel (diarrhoea)
- PBS approval for androgen receptor targeted therapy post-chemo (even though evidence for early use better ++):
. abiraterone (HTN, hypokalaemia, peripheral oedema, transaminitis) + pred to avoid excess corticosteroid.
. enzalutamide (HTN, fatigue, cognitive impairment and C/I seizures)
- Genetics: DNA repair defects (BRCA2 / 1) ?PARP inhibitors.
- PSMA (prostate specific membrane antigen) with Ga (diagnostic) and Lu (therapeutic).
Renal ca.
- Clear cell > Papillary > chromophobe / onocytoma.
- VHL controls HIF which promotes angiogenesis and cell proliferation, abnormal VHL leads to uncontrollable proliferation and cancer.
- IMDC risk score: Poor PS, high N°, high Plts, high Ca2+, low Hb, <12-mo between dx and tx
- Immunotherapy (CTLA4 + PD1 = Nivo + Ipi have autoimmune SE’s like addisons, thyroid etc) > sunatinib (TKI, VEGFR inhibitor have mucositis, diarrhoea, hand-foot syndrome, hypothyroid, transaminitis, CCF, MI) > mTOR inhibitors. CHECKMATE-214.
- Cytoreductive nephrectomy if large tumour, other size concerns. Otherwise equivalent to sunitinib.
Bladder ca.
- Urothelial (90%) > Non-urothelial (squamous, schistosomiasis and adenoca, tx like GI).
- Radical cystectomy.
- Cis/Gem.
- Cis-ineligible =
* ECOG ≥ 2
* CrCl < 60ml/min
* Grade ≥ 2 hearing loss (Gd 2: hearing loss but hearing aid not indicated)
* Grade ≥ 2 neuropathy (Gd 2: moderate sx, limiting instrumental ADLs)
* NYHA Class III or greater heart failure
- Immunotherapy good because lots of germline mutations.
Testicular ca.
- seminoma (b-HCG, single high dose cisplatin) = non-seminoma (AFP, b-HCG, worse prognosis, adjuvant BEP)
- surveillance priority.
Stroke: secondary prevention.
Heart failure.
HFpEF: MRA +/- ACEi or ARB (if ACEI C/I).
HFrEF: ACEI/ARNI + BB + MRA + SGLT2i + loop diuretic for fluid retention.
BNP >400
NT proBNP
- <50yo: >450
- <75yo: >900
- >75yo: >1800
CAD ax: CTCA or CMR with late gadolinium enhancement if HF with low-int pre-test probability of CAD.
Increased LV wall thickness: CMR / PET or bone scintigraphy (amyloid-TT).
Acute HF mx: O2 if <84% O2, NIV if hypoxic despite O2 and pulmonary congestion, IV vasodilators if SBP>90 to relieve congestion and inotropes if signs of peripheral hypoperfusion.
Chronic HF mx:
HFrEF = ACEI + BB + MRA.
PARADIGM-HF:
ARNI replace ACEI (36hr washout) or ARB in HFrEF, EF <40% despite max ACEI/ARB + BB (unless contraindicated) +/-
MRA to decrease mortality and hospitalisation.
. caution SBP<90-100
DAPA-HF: SGLT2i benefit independent of diabetes.
Inclusion: Sx HF, EF<40%, NT-proBNP elevated.
Exclusion: eGFR < 30 or hypotension SBP<95 or T1DM.
Decreased mortality, HF hospitalisation and CV death.
EMPEROR-Preserved study (Phase III trial) showed empagliflozin demonstrated clinically meaningful composite primary endpoint of CV death or HHF.
Ivabadrine HFrEF <35% HR >= 70bpm despite max doses ACEI/ARB + BB +/- MRA to decrease cardiovascular mortality and HF hospitalisation.
Hydralazine + nitrates (African)
Digoxin (SR and mod-severe NHYA304 despite max med mx)
N-3 polyunsaturated fatty acids.
Anaemia/IDA: Ferr <100 or 100-300 with trans sat <20%, IV iron. Not for EPO.
T2DM.
Monitoring important: how often, when, relation to meals / driving, targets
Insulin titration, carb counting, ratio (carb and glucose)
Complications:
- microvascular
- macrovascular
Mx priority:
1. Metformin
2. SGLT2i or GLP1-RA preferred.
IF CVD - SGLT2i
IF weight loss - GLP1-RA.
Path: insulin secretion < insulin resistance.
Complications:
Hypoglycemia <4.0
Hyperglycemia >13.0
Target pre-breakfast for T1DM: 4-6 and T2DM: 4-7.
-DKA: diabetic ketoacidosis, T1DM tx with insulin / glucose.
-HHS: hyperosmolar hyperglycemic state, T2DM tx with rehydration, avoid insulin to prevent cerebral glucose drop suddenly.
-BOTH: risk of tx (hypokal, hypophos, hypoglycemia).
Microvascular:
- retinopathy
- nephropathy
- peripheral neuropathy (length dependent, mononeuritis multiplex, autonomic)
Macrovascular:
- stroke
- IHD
- PVD (diabetic foot wounds, ulcers, charcot joints).
Management:
Glucose-lowering: HbA1c 6.5-7%, 8 if elderly.
Monotherapy: metformin + SU or insulin
Dual therapy:
A. SGLT2-i (-flozin) ketoacidosis:
1) volume depletion increases ketosis
2) glucagon secretion increases ketosis
B. GLP-1 RA (-glutide): weight loss
. dulaglutide
. semaglutide
SE: acute pancreatitis, renal impairment (dula eGFR>15, sema eGFR>30).
C. DPP4-inhibitor (-gliptin).
. linagliptin
Note. thiazolidinediones (glitazones) used less frequently due to risk of heart failure, weight gain, bladder cancer, hepatotoxicity, fractures.
Insulin:
-aspart: short acting
-novomix: BD dosing
-glargine: 24hrly
Spirometry
ABG
Interstitial lung disease
Spirometry: FEV1/FVC ratio reduced = obstructive lung dx.
. Extrathoracic obstruction, expiration preserved.
. Intrathoracic obstruction, inspiration preserved.
ABG: pH, PaO2 (80-100), paCO2 (35-45), HCO3- (compensation).
. A-a gradient = PaO2 - 1.25(PaCO2)
. Anion gap
ILD.
IPF = UIP (subpleural reticulation, traction bronchiectasis, apical-basal gradient, honeycombing). Mx- antifibrotics slow rate of progression (pirfenidone = TGFB, decreased fibroblast proliferation. SE: nausea, GIT, photosensitivity / nintedanib = tyrosine kinase inhibitor. SE: diarrhoea, weight loss, CVD, bleeding risk).
CTD associated ILD.
. RA-ILD = UIP.
. SSc=NSIP (ground glass changes).
Hypersensitivity pneumonitis = fibrotic / non fibrotic (diff from UIP with ground glass changes). Nintedanib if fibrosis.
Sarcoidosis = tx life threatening or organ threatening dx.
Occupational ILDs (coal workers pneumoconiosis, silicosis, asbestosis)
Note. Cause v radiological pattern.
Long case discussion format
Explain
Confirm
Target
Management
Follow up
New onset diabetes after transplant (NODAT)
Predisposing factors
-ethnicity
-FHx
-pre-diabetic
-obesity
Tacrolimus, steroids
Initial mx with insulin for titration.
CKD-BMD
Stage 3a CKD onwards
Biochemical changes
Bone changes
Vascular and soft tissue calcification
Management
Monitor biochemistry: calcium, phosphate and PTH, serum ALP.
- Phosphate binders
- Hyperparathyroidism: dialysis pt aim PTH levels 2-9x ULN.
A. Tx triggers:
. hyperphosphataemia
. high phosphate intake
. hypocalcaemia (caltrate)
. vitamin D deficiency (colecalciferol, calcitriol)
B. Cinacalcet (calcium sensing receptor improved)
C. parathyroidectomy.
c/o adynamic bone disease from rapid lowering.
Osteoporosis / osteomalacia / osteosclerosis.
- bone bx for renal osteodystrophy
- denosumab but risk of hypocalcemia
- PO bisphophonates if Stage 4
Mx: CKD stage 1-3 (as for gen pop).
Stages of CKD
1 > 90
2 < 90
3 - 3A < 60
- 3B < 45
4 <30
5 <15
Fitness to drive
Neurological
-seizures: 6 months on tx after first seizure, if recurrent in 6/12 then minimum 1 year post. 10 years for commercial.
-stroke: 4/52 and TIA = 2/52
Cardiac
- MI / PPM insertion / ICD change / DVT = 2/52
- CABG / valve / aneurysm / ICD insertion / cardiac syncope = 4/52
- PE / heart lung tplant = 6/52
- VAD = 3/12
- cardiac arrest / ICD insertion post arrest = 6/12
Syncope
- if vasovagal, no limitations
Dementia
- conditional
Diabetes
- insulin tx = 2 yearly review, retained awareness of hypo.
- end organ complications or severe hypoglycemia, reconsider.
Alcohol excess
- conditional license
- 1/12 abstinence, no end organ damage or cognitive consequences.
Visual / hearing impairments, frequent assessment.
Bariatric surgery
Maintaining fat free mass with exercise
Aerobic and resistance
Improves maintenance of weight loss
Improves energy levels
Clinical frailty score
1 very fit (exercise regularly)
2 well (exercise occasionally)
3 managing well (routine walking)
4 vulnerable (slowing down)
5 mildly frail (help with community ADLs)
6 moderately frail (dependent for community ADLs and some personal ADLs)
7 severely frail (dependent for personal ADLs)
8 very severely frail (completely dependent, unlikely to survive minor illness)
9 terminally ill (<6/12 life expectancy)
Simplified fried criteria:
-decreased grip strength (difficulty with daily life)
-unintentional weight loss (>5% past 3/12 or 10% past 6/12)
-low energy
-low physical activity
-slow walking speed
Mental health pointers
Depression 2/52
-low mood
-anhedonia
-impact on sleep, oral intake, function
-not explained by something else
-slowing of thought and physical movement, decreased concentration
-fatigue or loss of energy
-feelings of worthlessness or guit
Anxiety 6/12
-restless
-fatigued
-irritable
-difficulty concentrating
-muscle tension
-sleep disturbance
Bipolar disorder
-mania
-depression
Psychosis 1/12 of psychosis
-schizophrenia
-schizoaffective: + mood disorder most of the time
Borderline personality disorder
Narcissistic personality
Histrionic personality
Mx:
Antidepressants
Antipsychotics
Mood stabilisers
Risk of falls, teratogenic, increased suicidality on starting
Serotonin syndrome
Neuroleptic malignant syndrome
