BPH medications - alpha-1 blockers Flashcards
What is the general action of alpha-1 blockers?
Bind to and block the activation of adrenergic alpha-1 receptors
Causes smooth muscle relaxation
Name the common alpha-1 blockers used for BPH
Tamsulosin
Doxazosin
Terazosin
Silodosin
Alfuzosin
Apart from BPH, what else can alpha-1 blockers be used to treat?
HTN (e.g., doxazosin also used for mild to moderate HTN)
Phaeochromocytoma
What is the pharmacokinetic of tamsulosin?
Oral bioavailablity = 90%
Protein binding = 94-99% (mostly to alpha-1-acid glycoprotein)
Half-life = 14.9±3.9 hours
Metabolism = hepatic via mainly CYP3A4, 2D6
Excretion = 76% kidney via urine, 21% in faeces
What is the pharmacodynamic of tamsulosin?
Blocks alpha-1A and alpha-1D adrenoreceptors
About 70% of alpha-1 adrenoreceptors in the prostate are alpha-1A
What are the contraindications for alpha-1 blockers (i.e., alfuzosin, doxazosin, tamsulosin, terazosin)?
Severe hepatic impairment
Hx of postural hypotension
Hx of micturition syncope (i.e., fainting whilst peeing)
In which group of patients should you prescribe tamsulosin with caution?
Severe renal impairment - eGFR less than 30 mL/minute/1.73 m^2
After cataract surgery (risk of intra-operative floppy iris syndrome)
In elderly people
What is floppy iris syndrome?
Loss of muscle tone in the iris with
Symptom triad of
1. pupil constriction despite pre-operative dilatation with standard mydriatic drugs
2. fluttering and bellowing of iris stroma
3. marked tendency for the iris to prolapse towards the side port incisions
What are the common/very common side effects of tamsulosin?
dizziness
sexual dysfunction
What are the uncommon side effects of tamsulosin?
asthenia
constipation
diarrhoea
headache
nausea
palpitations
postural hypotension
rhinitis
skin reactions
vomiting
What are the rare/very rare side effects of tamsulosin?
angioedema
Stevens-Johnson syndrome
syncope
What are the frequency not known side effects of tamsulosin?
dry mouth
epistaxis
vision disorders.
What is the usual dose of tamsulosin modified-release preparations for BPH?
400 micrograms OD
What is the usual dose of doxazosin modified-release preparations for BPH?
initially 4mg OD
dose can be adjusted after 4 weeks
then increased if necessary to 8mg OD
N.B. use with caution in mild to moderate hepatic impairment, avoid in severe impairment
In which group of patients should you prescribe alfuzosin with caution?
Acute heart failure
Hx of QT-interval prolongation
Mild to moderate hepatic impairment (for immediate release preparations)
Renal impairment (for immediate release preparations)
After cataract surgery (risk of intra-operative floppy iris syndrome)
In elderly people
In which group of people should you not prescribe alfuzosin?
People with:
- severe renal impairment (eGFR < 30mL/minute/1.73m^2)
- hepatic impairment
In which group of people should you not prescribe doxazosin modified release tablets?
People with:
- GI obstruction
- oesophageal obstruction or any degree of stricture
In which group of people should you not prescribe doxazosin with caution?
In people with:
- HF
- pulmonary oedema due to aortic or mitral stenosis
- mild to moderate hepatic impairment
After cataract surgery (due to risk of intra-operative floppy iris syndrome)
In elderly people
In which group of people should you not prescribe terazosin with caution?
In people with mild to moderate hepatic impairment
After cataract surgery (due to risk of intra-operative floppy iris syndrome)
In elderly people
What are the common/very common side effects of alfuzosin?
Asthenia
Diarrhoea
Dizziness
Dry mouth
Headache
Malaise
N+V
Postural hypotension
Vertigo
What are the uncommon side effects of alfuzosin?
Abdominal pain
Arrhythmias
Chest pain
Drowsiness
Flushing
Oedema
Palpitations
Rhinitis
Skin reactions
Syncope
Visual impairment
What are the rare/very rare side effects of alfuzosin?
Angina pectoris
Angioedema
What are the frequency not known side effects of alfuzosin?
Cerebral ischaemia
Floppy iris syndrome
Hepatic disorders
Neutropenia
Priapism (long lasting painful erection - can cause permanent damage to the penis)
Thrombocytopenia
What are the common/very common side effects of doxazosin?
Arrythmias
Asthenia
Chest pain
Cough
Cystitis
Dizziness
Drowsiness
Dry mouth
Dyspnoea
GI discomfort
Headache
Increased risk of infection
Influenza like illness
Muscle complaints
Nausea
Oedema
Pain
Palpitations
Skin reactions
Urinary disorders
Vertigo
What are the uncommon side effects of doxazosin?
Angina pectoris
Anxiety
Abnormal appetite
Arthralgia
Constipation
Depression
Diarrhoea
GI disorders
Gout
Haemorrhage
Insomnia
MI
Abnormal sensation
Sexual dysfunction
Stroke
Syncope
Tinnitus
Tremor
Vomiting
Weight gain
What are the rare/very rare side effects of doxazosin?
Alopecia
Bronchospasm
Blurred vision
Flushing
Gynaecomastia
Hepatic disorders
Leucopenia
Malaise
Muscle weakness
Thrombocytopenia
What are the frequency not known side effects of doxazosin?
Floppy iris syndrome
What are the key drug interactions of alpha-blockers?
alpha blockers + phosphodiesterase-5 inhibitors (PDE5 inhibitor) e.g., sildenafil, tadalafil, or vardenafil = symptomatic hypotension
- to minimise the risk of postural hypotension, the person should be stable on the alpah-blocker before starting a PDE5 inhibitor
alpha-blockers + ACEi/CCB/Beta-blockers/nitrates/diuretics/moxisylyte = additive hypotensive effect
alpha-blockers + CYP3A4 inhibitors (e.g., clarithromycin, itraconazole and ritonavir) = increased exposure to tamsulosin, alfuzosin, doxazosin
Sources
https://cks.nice.org.uk/topics/luts-in-men/prescribing-information/alpha-blockers/
https://go.drugbank.com/categories/DBCAT000696
