PPT2 Flashcards
Outline some of the disorders of micturition
- Urgency urinary incontinence: associated with overactive bladder syndrome
- Stress urinary incontinence: due to urethral sphincter incompetence
- Mixed urinary incontinence: stress + urgency urinary incontinence
- Overflow incontnence: with continuous urine leakage, resulting from hypotonic bladder or bladder outlet obstruction producing urinary retention
Which group of patients are more prone to urge incontinence?
Older women
What is urge incontinence?
Sudeen , strong need to urinate AKA overactive bladder
Thought to occur due to detrusor overactivity leading to involuntary detrusor muscle contractions during bladder filling
Causes a strong urge to urinate and involuntary urination
What are the pharmacological options for urge incontinence?
- Muscarinic receptor antagonists: oxybutinin, tolterodine - inhibit actions of acetylcholine which functions via the parasympathetic nervous system to cause bladder contraction
- B3 adrenoceptor agonists: mirabegron
Discuss neurotransmitter release in the parasympathetic and sympathetic nervous systems
Parasympathetic nervous system: ACETYLCHOLINE pre and post ganglionic
Sympathetic nervous system: ACETYLCHOLINE pre ganglionic and NORADRENALINE post ganglionic
Which is the main muscarinic receptor subtype in the bladder?
M3 - acetylcholine binds to M3 receptors and causes contraction of the detrusor muscle
How does mirabegron work?
Stimulates B3 adrenoreceptors in the bladder trigone which flattens and lengthens the bladder base which facilitates urine storage
Adverse effects: increase in BP and HR - mirabegron is contraindicated in people with severe hypertension
What are the adverse effects of muscarinic blockade?
Dry mouth
Tachycardia
Constipation
Blurred vision
Urinary retention if there is bladde outflow obstruction
What type of incontinence occurrs when a person coughs or sneezes?
Stess incontinence
What is the cause of stress incontinence?
Urethral sphincter incompetence
What would be initially reccommended to a patient suffering with stress incontinence?
Pelvic floor muscle training for 8-12 weeks
When would drug therapy be recommended for stress incontinence?
If surgical treatment is not suitable
Drug therapy for stress incontinence is limited
Which surgical procedures are avalaible for stress incontinence?
- Surgical sling procedures: sling placed around the neck of the bladder to support it
- Colposuspension: stitches to vagina to hold it and support external sphincter when stress is placed upon it e.g. when sneezing
Which drugs are used to treat stress incontinence?
Duloxetine (SNRI)
- Reduces the frequency of incontinence episodes in 50% of those treated, recommended to those who are poor candidates for or averse to surgery
Enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphincter - allows for stronger external urethral sphincter contraction and therefore more pressure needed to overcome it
How can the severity of BPH be assessed?
International prostate severity score
Questions relating to: incomplete empyting, frequency, intermittency, urgency, weak stream and straining - rated 0-5
0-7 = mildly symptomatic
8-19 = moderately symptomatic
20-35 = severely symptomatic
What is the first therapeutic intervention for BPH?
Alpha blocker - tamsulosin
Alternatives: alfuzosin, doxazosin, terazosin
What is the mechanism of action of alpha blockers in BPH?
Most drugs in this class are highly selective for the a1 adrenoreceptor which are mainly found in the smooth muscle of blood vessels and the bladder (particularly the bladder neck and prostate)
Stimulation of the a1 adrenoreceptors causes smooth muscle contraction and blockade causes relaxation
Alpha1 blockers cause a reduced resistance to bladder outflow
They also cause vasodilation and thus a reduction in blood pressure
What can be offered in addition to alpha blockers for BPH?
5-alpha reductase inhibitor e.g. finasteride or dustasteride
What is the mechanism of action of 5-alpha reductase inhibitors?
Reduce the size of the prostate
5-alpha reductase usually converts testosterone to dihydrotestosterone which leads to prostate hypertrophy - blocking this leads to prostate shrinkage
Takes 6-12 months to provide symptomatic relief, more effective in men with larger prostates
What are the side effects of 5-alpha reductase inhibitors?
- Breast enlargement
- Breast tenderness
- Reduced libido
- Ejaculation disorders
- Impotence
Which drugs do 5-alpha reductase inhibitors interact with?
Verapamil and diltiazem - increase the concentrations of dultasteride (yellow alert)
What is an important consideration when prescribing 5-alpha reducatse inhibitors?
Pregnant women should not handle broken or damaged tablets and should not have unprotected sex with a man taking the tablets
Exposure of a male foetus to 5-a reductase inhibitors can cause abnormal development of the external genitals
What drugs can be used for prostate cancer?
Antiandrogens: flutamide
Gonadorelin analogues: leuprolide, goserelin, buserelin
Chronic administration of gonadorelin analogues results ina sustained suppression of pituitary gonatotropins, serum testosterone falls to levels comparable to surgical castration
What is the preferred initial approach for systemic therapy in patients with metastaic bladder cancer?
Platinum based chemotherapy
Which chemotherapy is urothelial cancer most sensitive to?
Cisplatin-based combination chemotherapy
Which drugs are used to treat renal cell carcinoma?
Tyrosine kinase inhibitors: sunitinib, sorafenib
mTOR inhibitors: everolimus
Tyrosine kinase receptor inhibitors: bevacizumab
In what forms can oral iron be given?
- Ferrous sulphate
- Ferrous fumarate
- Ferrous gluconate
*little difference in Hb regeneration between the three so choice is made based on incidence of side effects and cost
What are the forms of parenteral iron?
Iron dextran
Iron sucrose
Ferric carboxymaltose
Iron isomaltoside 1000
*reserved for patients who cannot tolerate oral iron or if there is continuing blood loss or malabsorption
Discuss iron absorption
What transports iron from the enterocyte into the circulation?
Ferroportin protein
What regulates iron transport from enterocytes?
Hepcidin - peptide hormone (synthesised in the liver)
When circulating and tissue iron levels are high hepcidin synthesis is increased, it binds to ferroportin and leads to its degredation
Hypoxia, increased erythropoiesis and iron deficiency lead to the suppression of hepcidin and thus promote iron absorption
What are ferric iron ions bound to in the blood?
Aptotransferrin (a globulin)
How is the majority of iron stored?
Complexed with aptoferritin and stored as ferritin
What is haemosiderin?
An iron storage complex
insoluble aggregates of degraded forms of ferritin
What proprtion of iron is found in RBCs?
2/3
1/2 of the remainder is found in macrophages, reticuloendothelial cells and hepatocytes, the rest is present in myoglobin in muclse cells
Through which system are ageing RBCs broken down?
Reticuloendotheial system
Most of the released iron is recycled via macrophages
How is iron lost from the body (apart from bleeding)?
Iron loss from the body rarely happens, when it does occur it is mainly via shedding of mucosal cells that contain ferritin
What are the adverse effects of oral and parenteral iron?
Constipation, diarrhoea, epigastric pain, faecal impaction, GI irritation, nausea
What are the drug inractions of iron?
Iron reduced the absoprtion of:
Levothyroxine
Bisphosphonates
Ciprofloxacin
Tetracyclines
Calcium and zinc salts
*advise patients to take this medications at least two hours before they take oral iron
What should the daily dose of elemental iron be?
100-200mg dialy
Ferrous fumarate 200mg = 65mg elemental iron
Ferrous gluconate 300mg = 35mg elemental iron
Ferrous sulphate 200mg = 65mg elemental iron
By how much should oral iron supplements raise blood Hb?
20g/L over the first 3-4 weeks and then 10g/L per week thereafter
Oral iron should be conitnued for 3 months after the Hb conc. has been restored in order to replenish iron stores
What is the difference bwteen folate and folic acid?
Folate: water soluble vitamine B9 that occurs naturally in foods such as beef liver, leafy veg, oranges, legumes
Folic acid: synthetic form of folate found in food supplements and added to fortified foods
Why is folic acid supplementation recommended to proegant women or women planning to get pregnant?
Reduces risk of neural tube defects
Folid acid may enchance cell proliferation for neural closure
What is folate required for?
DNA synthesis
Cell replication
Formation of RBCs
What form is folate in in the circulation?
5-methyltetrahydrofolate (5-MeTHF)
Which women are most at risk of having a child with a neural tube defect?
- Previous child with a NTD
- Taking anti-convulsants such as valproate and carbamazepine
BUT 95% of those who have children with a NTD are not in the high risk group
Discuss folate supplementation in women at high risk of having a child with a NTD
Pre-conception: 5mg daily
then 5mg daily until week 12 of pregnancy
Reduces the risk by ~70%
Discuss folate supplementation in females wanting to get pregnant
400ug daily before conception up to week 12 of pregnancy
Folic acid supplementation and sickle cell disease
Patient should continue taking folic acid (5mg) before conception and throughout pregnancy
Why is folic acid supplementation advised for all women of childbearing age?
Most pregnancies are unplanned
What is subacute combine ddegeneration of the cord?
AKA Lictheim’s disease - degeneration of posterior and lateral columns of the spinal cord due to B12 deficiency
Usually presents with loss of vibration and proprioception of hands and feet and eventual total sensory loss, features of dementia may also be present
* if treating a macrocytic anaemia where there may be a B12 deficiency, always give B12 before starting folic acid
When treating a macrocytic anaemia due to B12 deficiency, how is hydorxycobalamin given?
IM - the vast majority of vitamin B12 deficiency is due to the inability to absorb B12 in the terminal ileum
Oxybutinin
Tolterodine
Doxazosin
Tamsulosin
Dutasteride
Finasteride
Cisplatin
Sunitinib
Bevacizumab
Goserelin
Cyproterone acetate
Sildafenil
Tadalafil
Alprostadil
Ferrous sulfate
Iron sucrose
Hydroxycobalamin
Folic acid
Darbepoetin
