Give examples of alpha blockers and what that drug is given to treat?
- Doxazosin (BPH and HTN)
- Tamsulosin (BPH)
What are the main indications for alpha blockers?
- Benign prostatic hyperplasia
- add on treatment for resistant HTN
What is the MOA of alpha blockers?
Highly selective for the alpha1-adrenoreceptors.
Bind and inhibit alpha1-adrenoceptors in smooth muscle (including blood vessels & urinary tract – bladder neck and prostate in particular) causing muscle relaxation:
- Vasodilation
- Fall in BP
- Reduced resistance to bladder outflow
what are the main side effects of Alpha Bloackers?
Side effects are as a result of the effects on vascular tone:
- Postural Hypotension
- dizziness
- syncope
What are the contraindications of alpha blockers?
- Postural Hypotension
What are the key drug interactions of alpha blockers?
- Antihypertensive drugs
Give some examples of anti-muscarinics?
- Oxybutynin
- Solifenacin
What are anti-muscarinics indicated in?
1st line treatment in overactive bladder to reduce urinary:
- Frequency
- Urgency
- Urge incontinence
What is the MOA of Anti-muscarinics?
- Bind muscarinic receptors (M3 in bladder) and acts as a competitive inhibitor of acetylcholine (which contracts the bladder) to then promote bladder relaxation which increases bladder capacity and reduces urinary frequency, urgency and urge incontinence in overactive bladder.
What are the main side effects of anti-muscarinics?
- Dry mouth
- constipation
- tachycardia
- Blurred vision
- urinary retention if there is an outflow obstruction.
What are the key contraindications of anti-muscarinics?
- UTI
- elderly
- dementia
- Pts susceptible to acute-angle glaucoma due to risk of rising intraocular pressure.
- Pts at risk of arrhythmias
- Pts at risk of urinary retention
What are the key drug interactions of anti-muscarinics?
- other anti-muscarinics e.g., tricyclic antidepressants
Give an example of Phosphodiesterase type 5 inhibitors?
Sildenafil
What are the main indications for prescribing Phosphodiesterase type 5 inhibitors?
- erectile dysfunction
- primary pulmonary hypertension
What is the MOA of Phosphodiesterase type 5 inhibitors?
Selective for PDE Type-5 (PDE-5) - found in smooth muscle of the:
- Corpus cavenosum of the penis
- Arteries of the lung
Sexual stimulation releases nitric oxide (NO) which stimulates cGMP production causing:
- arterial smooth muscle relaxation
- vasodilation
- penile engorgement
- Inhibition of PDE-5 prevents the breakdown of cGMP which
increases cGMP concentrations and improves penile blood flow and erection quality - Causes arterial vasodilation in pulmonary vasculature
What are the main side effects of Phosphodiesterase type 5 inhibitors?
Due to vasodilator action:
- Flushing
- Headaches
- Dizziness
- Nasal congestion
- Hypotension
- Tachycardia
- Palpitations
- Small risk of associated vascular events e.g. MI/ Stroke
- Visual disorders (including colour distortion due to inhibition of PDE-5 in the retina) urgent medical review
What are the key interactions of Phosphodiesterase type 5 inhibitors?
Drugs that increase NO concentration e.g.,
- Nitrates
- Nicorandil
^^ combined effects on cGMP can cause marked arterial vasodilatation and cardiovascular collapse
Use with caution with other vasodilators due to increased risk of hypotension e.g.
- Alpha blockers (should not be take within 4h)
- Calcium channel blockers
Cytochrome P450 inhibitors can increase plasma concentrations and adverse effects of sildenafil e.g.
- Amiodarone
- Diltiazem
- Fluconazole
What are the key contraindications of Phosphodiesterase type 5 inhibitors?
Avoid where vasodilation can be dangerous, including:
- Recent stroke
- Recent ACS
- History of CVS disease.
Avoid/ lower dose in pts with:
- Hepatic impairment )
- Renal impairment
Give and example of 5 alpha reductase inhibitor?
Finesteride
What are the main indications of 5-alpha reductase inhibitor?
- 2nd line for BPH
- LUTs
Side effects of 5-alpha reductase inhibitors:
Relate to their antiandrogen action:
- Impotence (transient)
- Reduced libido (transient)
- Breast tenderness
- Gynecomastia
- Hair growth
Rare:
- Breast cancer in men
What is a key contraindication of Finesteride?
- Pregnant women should not even be exposed to them e.g. by handling broken or damaged tablets, or through semen during unprotected sex with a man taking these drugs can cause abnormal development of the external genitalia in a male foetus
