Renal and urology pharmacology Flashcards
Alpha 1 blockers
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
Tamsulosin, Doxazosin, alfuzosin
Common indications
- BPH (along with 5alpha reductase)
- Resistant hypertension
Mechanisms of action
- Act against alpha 1 receptors in smooth muscles of BV and urinary tract flow-> vasodilation and decrease resistance to urinary flow
important adverse effects
- postural hypotension, dizziness, syncope
warnings
- Don’t use in those with postural hypotension
important interactions
- Don’t use with other BP lowering medication
5 alpha reductase inhibitors?
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
- Finasteride
Common indications
- Benign prostate hyperplasia
Mechanisms of action
- Inhibit 5 alpha reductase to prevent conversion of testosterone to DHT (important in prostate growth)
important adverse effects
- reduced libido, impotence, gynaecomastia and risk of breast cancer (increase conversion of T to oestradiol)
warnings
- Cannot give those who are pregnant with male foetus (abnormal development of external genitalia)
important interactions
Calcium and vitamin D?
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
- Oral calcium carbonate, IV calcium gluconate, cholecalciferol (D3), alfacalcidol/calcitriol (1,25 D3)
Common indications
- osteoporosis: both calcium and vitamin D given to increase bone density
- CKD disease: both calcium and vitamin D (alfacalcidol) given to increase serum calcium and prevent renal osteodystrophy
- hypocalcemia
- hyperkalaemia: IV calcium gluconate given to stabilise cardiac membrane due to arrhythmias (with insulin, glucose)
- vitamin D deficiency like rickets in children or osteomalacia in adults
Mechanisms of action:
-important for function of muscles, nerves, bones and clotting
important adverse effects
- oral calcium carbonate can cause dyspepsia and constipation
- IV calcium gluconate can cause cardiovascular collapse when adminstered to quickly, or local tissue damage in subcutaneous layer
warnings:
-do not give in those with hypercalcemia
important interactions
- oral calcium carbonate interacts with iron, biphosphonates, tetracycline, levothyroxine
- IV calcium gluconate interacts with sodium bicarbonate
Genitourinary antimuscarinics
Common indications
Mechanisms of action
important adverse effects
warnings
important interactions
Oxybutynin, Tolterodine, solifenacin
Common indications
- Urge incontinence
Mechanisms of action
- Inhibit Ach at M3 muscarinic receptor-> preventing detrusor muscle from contracting and preventing you from peeing
important adverse effects
- Pupil dilatation and blurry vision
- Tachycardia
- Reduced secretion from Resp and GI tract-> constipation and dry mouth
warnings
- Don’t give to those w UTI or urinary obstruction as will worsen this
- Don’t give to those with angle-closure glaucoma
important interactions
A 48-year-old man is found to be hyperkalaemic. One month ago he was admitted to hospital with a non-ST-elevation myocardial infarction, for which he underwent percutaneous intervention. His medications, which were all started during the recent hospital admission, comprise aspirin, clopidogrel, atorvastatin, bisoprolol and ramipril.
What drug is most likely to cause hyperkalaemia?
Aspirin
Atorvastatin
Bisoprolol
Clopidogrel
Ramipril
- Ramipril (ACE inhibitor causes hyperkalaemia)
Ramipril. ACE inhibitors (e.g. ramipril) commonly cause an increase in the serum potassium concentration. This can usually be tolerated provided it does not exceed 6.0 mmol/L. Other drugs with a significant potassium-elevating effect include angiotensin-receptor blockers, aldosterone-receptor antagonists, oral and intravenous potassium supplements, and potassium-sparing diuretics. Beta-blockers and aspirin can also increase the potassium concentration, but this effect is not usually significant. Statins and clopidogrel do not cause hyperkalaemia.
A 61-year-old man with benign prostatic hyperplasia is advised to take tamsulosin to improve urinary flow.
What side effect is most likely to occur when starting this new drug?
Bronchospasm
Postural hypotension
Erectile dysfunction
Gynaecomastia
Prostate cancer
- Postural hypotension (alpha blocker)
Postural hypotension. Tamsulosin (an α-blocker) blocks α1-adrenoceptors in the smooth muscle of the prostate gland, increasing urinary flow and relieving obstructive symptoms. As α1-adrenoceptors are also found in the smooth muscle of blood vessels, α-blockers can cause hypotension, particularly postural hypotension. Patients taking other antihypertensive medication should be especially vigilant to these effects and may need to omit their usual treatment when starting an α-blocker. Bronchospasm and erectile dysfunction are adverse effects of β-blockers(not α-blockers). Tamsulosin does not cause gynaecomastia or prostate cancer.
An 82-year-old man with COPD is breathless and has recurrent exacerbations. His past medical history includes an episode of urinary retention secondary to benign prostatic hyperplasia.
Prescription of what drug requires a cautious approach in this patient?
Salbutamol
Salmeterol
Seretide®
Symbicort®
Tiotropium
- Tiotropium (antimuscarinic prevents voiding and causes urinary retention)
E. Tiotropium. Tiotropium is a long-acting antimuscarinic bronchodilator. Its side effects include urinary retention in people susceptible to this. It should therefore be avoided or used cautiously in patients with a history of urinary retention, or risk factors such as benign prostatic hyperplasia.
Salbutamol and salmeterol are, respectively, short- and long-acting β2-agonists. Seretide® and Symbicort® are compound β2-agonist–corticosteroid inhalers. Warnings regarding their use can be reviewed under the relevant individual drug entries.
A 33-year-old man with severe renal impairment requires antibiotic treatment for sepsis.
What antibiotic can generally be used without dosage reduction in severe renal impairment?
Benzylpenicillin
Co-amoxiclav
Doxycycline
Gentamicin
Metronidazole
E. Metronidazole. Metronidazole is metabolised and eliminated by the liver. Dosage reduction is therefore required in severe hepatic impairment rather than renal impairment.
Many other antibiotics are eliminated by the kidney. In patients with renal impairment they may therefore accumulate, increasing the risk of adverse effects. However, there is always a balance to be struck between the risk of drug toxicity and the risk of undertreating the infection. As such, renal impairment does not necessarily contraindicate the drugs’ use, but it does mandate a more cautious approach to drug selection and dosing regimens.
In severe renal impairment, dose reductions are required with penicillins such as benzylpenicillin and co-amoxiclav due to the risk of central nervous system toxicity, including fits; tetracyclines such as doxycycline due to the risk of hepatotoxicity and nephrotoxicity; and aminoglycosides such as gentamicin, which may cause ototoxicity and nephrotoxicity.
A 67-year-old man presents to the general practice to discuss his medication. For several years he has been taking sildenafil for erectile dysfunction. He has previously found this to be an effective and tolerable treatment, but says it has recently been causing headaches.
He has a past medical history of chronic obstructive pulmonary disease. In addition, he was recently found to have atrial fibrillation. His treatment has been adjusted frequently over the past few weeks. His regular treatment now comprises digoxin, diltiazem, simvastatin, tiotropium and warfarin. Examination is normal other than for an irregular pulse at a rate of 80–90 beats/min.
What drug is most likely to interact with sildenafil to provoke side effects?
Digoxin
Diltiazem
Simvastatin
Tiotropium
Warfarin
B. Diltiazem. Sildenafil is a phosphodiesterase (type 5) inhibitor. It is metabolised by a member of the cytochrome P450 enzyme family called CYP3A4. Diltiazem is a calcium channel blocker that inhibits CYP3A4 activity. If the drugs are taken together, the metabolism of sildenafil will be reduced such that the patient is exposed to higher sildenafil concentrations. This increases the chance of dose-related adverse effects, such as headache. A reduced dose of sildenafil is recommended in patients taking cytochrome P450 inhibitors, other examples of which include amiodarone and macrolide antibiotics.
Diltiazem can also interact with digoxin, since they both reduce conduction at the atrioventricular node. This interaction may be exploited therapeutically, as in this case, to slow the ventricular rate in patients with atrial fibrillation. There are no other clinically significant interactions between the drugs listed.
A 72-year-old woman is found to be hypokalaemic. She had an elective right knee arthroplasty 3 days ago. Over the last 24 hours she has developed vomiting and abdominal pain. Viral gastroenteritis is suspected, as other patients on the ward have been affected by the same symptoms.
On examination, her pulse is 88 beats/min and her blood pressure is 156/90 mmHg. Her mucous membranes are dry. Her serum potassium concentration is 2.3 mmol/L (3.5–4.7). The rest of her serum biochemistry is normal. The ECG shows small T waves.
What is the most appropriate initial treatment?
Co-amilofruse 5/40 1 tablet orally
Potassium chloride 40 mmol in 1 L of sodium chloride 0.9% IV over 2 hours
Potassium chloride 40 mmol in 1 L of glucose 5% IV over 1 hour
Potassium chloride/bicarbonate (Sando-K®) 3 tablets orally
Ramipril 5 mg orally
Show Answer
Potassium chloride 40 mmol in 1 L of sodium chloride 0.9% IV over 2 hours
B. Potassium chloride 40 mmol in 1 L of sodium chloride 0.9% IV over 2 hours. Hypokalaemia is a potentially dangerous electrolyte abnormality due to its association with arrhythmias. A serum potassium concentration <2.5 mmol/L is generally deemed to be ‘severe’, and this warrants intravenous treatment. In a general ward environment, this is administered through a peripheral cannula using a potassium-containing fluid. Option B, containing potassium chloride 40 mmol/L, is a reasonable choice.
Option A is a combination of a loop diuretic (furosemide) and a potassium-sparing diuretic (amiloride). If hypokalaemia occurs during treatment with furosemide, exchanging it for co-amilofruse may resolve this. It is not suitable for treatment of other causes of hypokalaemia. Option C is inappropriate because the rate of intravenous potassium administration is too fast: it should not exceed 20 mmol/hr on a general ward. Also, it is usually better to treat hypokalaemia using a sodium-chloride-based fluid than glucose (see Potassium, intravenous). Option D, potassium orally, is the preferred treatment for non-severe hypokalaemia. Option E, an ACE inhibitor, does have a potassium-elevating effect. However, it is not an appropriate treatment for acute hypokalaemia. Indeed, ACE inhibitors should be avoided whenever there is a risk of acute kidney injury, such as in patients who have become dehydrated.
A 73-year-old woman is advised to take oxybutynin to improve her symptoms of urinary urgency and urge incontinence.
What best describes the mechanism of action of oxybutynin?
Agonist at the β2-adrenoceptor
Antagonist at the muscarinic M3 receptor
Antagonist at the nicotinic acetylcholine receptor
Antagonist at the α1-adrenoceptor
Inhibitor of 5α-reductase
B. Antagonist at the muscarinic M3 receptor. Oxybutynin is an antimuscarinic drug that preferentially blocks the M3 receptor in the bladder. This inhibits the procontractile effect of parasympathetic stimulation, causing relaxation of the bladder smooth muscle and increasing bladder capacity. This makes it a useful option for treatment for urge incontinence and overactive bladder symptoms.
Alpha1-blockers (e.g. doxazosin) and 5α-reductase inhibitors(e.g. finasteride) are used to treat symptoms of benign prostatic hyperplasia. They have no role in the treatment of overactive bladder. Beta2-agonists are used to induce smooth muscle relaxation in the airways; they are not used for overactive bladder. The nicotinic acetylcholine receptor is involved in neuromuscular transmission in skeletal muscle. Antagonists of this receptor are used in anaesthetic practice to induce muscle relaxation.
A 92-year-old woman, who lives in a residential home for people with dementia, is found confused and wandering. Her caregivers think that this was precipitated by a medicine for ‘overactive bladder’, which was started last week. Unfortunately they cannot find the drug in her room as she has been hiding things, and the GP surgery is closed.
What drug is most likely to have caused her confusion?
Finasteride
Furosemide
Solifenacin
Tamsulosin
Trimethoprim
C. Solifenacin. Solifenacin is an antimuscarinic drug used to treat urinary urgency and urge incontinence. Side effects of antimuscarinics include dry mouth, blurred vision, constipation and confusion. Elderly patients, especially those with dementia, are particularly vulnerable to these side effects. The reasons for susceptibility to confusion are complex but include alteration in drug distribution and metabolism as well as increased sensitivity to their central nervous system effects. Where possible, alternative therapies should be used.
The other drugs listed are unlikely to have been started in this case. Finasteride is a 5α-reductase inhibitorand tamsulosin is an α-blocker; they are both used in men with benign prostatic hyperplasia, but not in overactive bladder. They are not known to cause confusion. Furosemide is a loop diuretic used in states of fluid overload such as heart failure, and does not directly cause confusion (although over-diuresis leading to dehydration might). Trimethoprim is an antibiotic that acts by interfering with bacterial folate synthesis. It is commonly used to treat urinary tract infections, but not overactive bladder. It causes confusion very rarely.
