Polycythemia

Polycythemia

Primary polycythemia/ Polycythemia vera

  • a.k.a polycythemia rubra vera; erythremia
  • common in age 60 – 75
  • overproduction of all three hematopoietic cell lines with predominant elevation in red cell counts
  • mutation in the JAK2 protein which regulates marrow production
  • red cells grow wildly despite a Low erythropoietin level
  • high serum leukocyte alkaline phosphate
features:
  • Headache, blurred vision, and tinnitus
  • pruritus, especially after hot bath (due to histamine release from increased numbers of basophils)
  • HTN, facial plethora, fatigue, Splenomegaly
  • Bleeding from engorged blood vessels
  • Thrombosis from hyperviscosity
Investigation,
  • elevated Hct >60%*
  • low MCV and Low iron (because of excessive usage and production)
  • however, Vit. B12 levels are elevated for unclear reason
  • exclude hypoxia first; normal Oxygen level and *low erythropoietin level in PV
* RCC also has elevated Hct, but the erythropoietin is elevated.
* A small number of patients can convert to AML.
Tx
  • initial 1st line – Phlebotomy and aspirin prevent thrombosis – target Hct 45%
  • Hydroxyurea helps lower the cell count
    • indicated in old age >70 years; has thrombosis; has a platelet count >1500; and has cardiovascular risk factors
  • Allopurinol or rasburicase protects against uric acid rise
  • Antihistamines
  • Interferon alpha may be used in refractory cases
Platelet counts elevate temporarily after spleen removal

Secondary polycythemia
Increased erythropoietin level
2° to chronic tissue hypoxia
 

Kidney cancer is an important differential diagnosis of secondary polycythemia.

Renal Cell Carcinoma is a neoplastic condition that can initially appear with many different paraneoplastic manifestations.

The initial presentation may include hypertension, flank mass, gross or microscopic hematuria, hypercalcemia, fever, weight loss, and/or polycythemia.

Polycythemia may be the presenting sign in 3% of cases of kidney cancer.

Careful evaluation is important in patients presenting with polycythemia and hematuria.

Polycythemia is secondary to a hypersecretion of tumor cytokines, including renin.

The patient’s erythropoietin level is usually high.

Surgical removal of the cancer resolves the polycythemia.

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Pharmacology for Urology

When I was in Urology as a SHO (senior house officer), I have learned my cases and the medications that are used particularly in those urological conditions. So, I made a note for quick review and recall which could be helpful for other junior doctors like me.

First, the two most commonly used drugs in BPH are 5-alpha reductase inhibitors and the alpha blockers. 5-alpha reductase inhibitors have prostate volume reduction effect or apototic effect but the latter have not. However, it takes about 6 months to show the effect of 5-alpha reductase inhibitors and so alpha 1 blockers are used as first line symptomatic agents.

5-alpha reductase inhibitors

Dutasteride and Finasteride – inhibits the conversion of testosterone to dihydrotestosterone; used in combination with alpha-blockers in many cases

Dutasteride (Avodart)dual 5-alpha reductase inhibitor

– 0.5 mg po od

Finasteride (Proscar -5mg and Propecia-1mg) (type 2) 5-alpha reductase inhibitor

– 5mg po od; (1mg od is used in male pattern baldness MPB)

SE –
impotence (1.1% to 18.5%), abnormal ejaculation (7.2%), decreased ejaculatory volume (0.9% to 2.8%), abnormal sexual function (2.5%), gynecomastia (2.2%), erectile dysfunction (1.3%), ejaculation disorder (1.2%) testicular pain and depression. * ?increased risk of high-grade prostate cancer.

pregnancy category X – Mom ! don’t touch the pill, beware of blood transfusion

Alpha Blockers

Selective alpha-1 blockers – Doxazosin, Tamsulosin, Terazosin etc. – inhibits the binding of norepinephrine to the alpha-1 receptors on the membrane of vascular smooth muscle cells

Doxzosin mesylate ( Cardura, Carduran)

Dose: 1mg >>2mg>>4mg>> 8mg (max dose)/day.

Tamsulosin (Flomax, Flomaxtra, Contiflo XL and Urimax) 0.4mg >> 0.8mg od

Two major ADRs (Adverse Drug Reactions) :

  • Immunologic: contains sulfa moiety causing typical reactions to sulfa drugs.
  • Ophthalmologic: ” floppy iris syndrome” during cataract surgery.

Others : Retrograde ejaculation, dizziness and fainting due to BP drop.

N.B. Although prostate specific, it does not have the prostate apoptotic effects of other prostate drugs such as the 5 alpha-reductase inhibitors such as dutasteride and finasteride.

Trial

CombAT (Combination of Avodart and Tamsulosin) trial in 2008,- approved by the FDA on June 14, 2010

provides greater symptom benefits compared to monotherapy with either agent alone for treatment of benign prostatic hyperplasia.

Anticholinergics

Oxybutynin and Tolteredine

Oxybutynin – competitively antagonizes the M1, M2, and M3; also has direct spasmolytic effects on bladder smooth muscle as a calcium antagonist and local anesthetic in very high dose

– used in Overactive bladder/ urinary incontinence; possible treatment of hyperhidrosis

N.B. There was no difference in transdermal oxybutynin and extended-release oral tolterodine.

Contraindications

Untreated angle closure glaucoma and in patients with untreated narrow anterior chamber angles;  partial or complete bowel obstruction, hiatal hernia, GERD, paralytic ileus, intestinal atony of the elderly or debilitated patient, megacolon, toxic megacolon complicating ulcerative colitis, severe colitis and myasthenia gravis. It is also contraindicated in patients with obstructive uropathy and in patients with unstable cardiovascular status in acute hemorrhage.

Tolterodine (DetrolDetrusitol) – acts on M2 and M3

Hormone therapy

Cyproterone acetate CPA (Androcur or Cyprostat) – synthetic steroidal antiandrogen and also has progestogen and antigonadotrophic properties

Uses

1) in OC pills (2mg of CPA +35 or 50mg ehtinyestradiol),

2) hypersexuality, hirsutism, male-female transsexuals (25mg po.bd, up to 100mg/day)

3) metastatic Prostate CA (300mg/day), monitor LFTs, often co-administered with a GnRH agonist and a 5-alpha-reductase inhibitor

SE:  liver toxicity (dose dependent), adrenal suppression (so, monitor cortisol level and U&Es), often co-administered with a GnRH agonist and a 5-alpha-reductase inhibitor

Flutamide – oral, non-steroidal antiandrogen drug, has been largely replaced by Bicalutamide (Casodex, Cosudex, Calutide, Kalumid) –

Uses

1) stage D2 metastatic prostate cancer in combination with a LHRH analogue or as a monotherapy.

2) hirsutism, trials in Ovarian CA , also used in combination with castration

3) andogen receptor positive ER-/PR- metastatic breast cancer

Dose – 50mg po od (recommended same time each day)

Leuprolein or Leuprolide acetate -pituitary GnRH analogue

Pregnancy Category X

Uses: Hormone responsive cancers (Prostate CA, breast CA),

Use in Gynecology – precocious puberty, gender incongruency,  menorrhagia, endometriosis, adenomyosis, Uterine fibroids, in IVF(in vitro fertilization) – control of ovarian hyperstimulation,

Severe cases of CAH (congenital adrenal hyperplasia)

also, possible treatment for Paraphilia and Alzheimer’s dz

SE: s/s of hypo-estrogenism such as headache, hot flushes and osteoporosis

increased risk of heart problems by ~30% (when used for advanced CA Prostate)

Urinary Alkalinizing Agents

Potassium citrate (Cytra-K, Urocit K)

Urinary citrate <150 mg/day: 60 mEq/day PO (20 mEq with each meal) OR

Urinary citrate >150 mg/day: 30 mEq/day PO (10 mEq with each meal)

Maintenance –

  • Titrate dose to achieve urinary citrate 320-640 mg/day & urinary pH 6.0-7.0 (maximum dose 100 mEq/day)

Local Analgesic

Phenazopyridine – Azo dye; 100mg-200mg po tid (no more than 2 days)

used in severe dysuria;  post-procedures

Bleeding control

tranexamic acid (Cyklokapron, Lysteda) – Inhibits fibrinolysis through inhibition of plasminogen activator substances; also exhibits antiplasmin activity

used in conjunction with bladder irrigation in hematuria cases

Alright, I think you should be ready to go to urology unit by now. Good Luck!

N.B. I have also used Doxorubicin (Adriamycin) in many cases with TCC bladder; it is an Anthracycline that intercalates between DNA base pairs, impairs topoisomerase II function and inhibits replication & transcription

Add other drugs and noteworthy facts in the comments below please.

What blood group you are ?

Does anybody aware of the fact that your blood group itself is a minor risk factor for certain type of diseases?

Here it comes –

  1. Individuals with blood groups A, B, or AB were 5% to 23% more likely to develop coronary heart disease compared with subjects with O blood type, and the associations were not altered by multivariate adjustment of other risk or dietary factors. (The analysis, led by Dr Meian He (Harvard School of Public Health, Boston, MA), included 62 073 women from the Nurses’ Health Study (NHS) and 27 428 men from the Health Professionals Follow-up Study (HPFS) and is published in the September 2012 issue of Arteriosclerosis, Thrombosis, and Vascular Biology.)
  2. Rotavirus (that causes diarrhea) has certain strains which are more likely to infect people with blood type A.
  3. People with type B blood have a 72 percent increased risk of pancreatic cancer, and the risk is also elevated for AB blood types (51 percent) and those with blood type A (32 percent) compared to people with blood type O, according to a study published in the Journal of the National Cancer Institute.
  4. For the women with blood type A and AB seeking fertility treatments—research shows they have more eggs in their ovaries than women with type O blood, who are more likely to have difficulty with fertility treatments.
  5. People with type A blood appeared to have higher incidences of breast cancer and lung cancer, blood types B and O were more likely to suffer from gastrointestinal cancer, and people with type B and A blood had higher incidents of oral cancer. In general, those with blood type A seemed to have an increases probability of getting cancer, and those with blood type O had a significantly lower risk.
  6. Patients with blood Group A have a higher chance to develop gastric cancer while those with Group O can easily get Peptic ulcer disease especially duodenal ulcer.

Well, I am group A and all those researches are saying I am more likely to get coronary heart disease, diarrhea and some GI tract cancers than any other blood types! And as you all know, doctors, especially junior doctors, are prone to get gastritis and heart problems  because of the nature of the work, stress and duty hours. It shocked me. Since this is  a non-modifiable risk factor, all I can do is to reduce the other risk factors such as smoking, heavy drinking, unhealthy eating habit and sedentary life style and finally, of course, to pray.
What about you?

 

Source:

http://health.yahoo.net/experts/dayinhealth/what-your-blood-type-reveals-about-your-health

http://www.ncbi.nlm.nih.gov/pubmed/20937632