Regular, long-term prescription of anticholinergics increases the risk of:
D. Anticholinergic drugs may exacerbate some symptoms of tardive dyskinesia (TD). Traditionally, long-term anticholinergic prescriptions are thought to promote the onset of TD, though the evidence in support of this notion is minimal. Tardive dyskinesia is a troublesome side effect of antipsychotics. It is more common in older patients and those with neurological diseases. The risk of tardive dyskinesia is estimated as 3–5%per year of exposure (at least for the first 5 years) with conventional antipsychotics. The appearance of symptoms usually takes more than 3 months, the risk increasing proportionally with duration of treatment. In elderly patients this increases to be as high as 25% within the first year of exposure to typical antipsychotics. Women, children, and patients with primary mood disorders or learning disabilities are also at higher risk. Some studies report an increased risk associated with diabetes and comorbid substance use.
Reference:
Select one drug associated with gastrointestinal bleeding:
B. Serotonin is released from platelets in response to vascular injury. It promotes vasoconstriction and platelet aggregation. Platelets do not possess the synthetic machinery to produce serotonin and so depend on uptake via 5-HT transporters on their membrane. SSRIs inhibit the serotonin transporter, leading to a hypo-serotonergic state in platelets. This reduces the ability to form clots, with subsequent increase in the risk of bleeding. Thus, SSRIs cause a functional impairment of platelet aggregation (thrombasthenia), but not a reduction in platelet number. This can cause easy bruising or prolonged bleeding in those with gastric ulcers or bleeding diathesis. Some authors recommend gastr-oprotection when SSRIs are coadministered with NSAIDs.
Which of the following is a partial agonist at nicotinic acetylcholine receptors that can be used to promote smoking cessation?
A. Varenicline is a partial agonist at the α4 β2 unit of the nicotinic acetylcholine receptor. It is shown to assist smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine. It is advised to choose a quitting date and start taking the tablets 1 week before the date. Generally, varenicline is started at 0.5 mg daily, increasing to 0.5 mg twice daily after 3 days. The final dose is 1 mg twice daily for up to 12 weeks.
A 48-year-old man taking multiple drugs for hypertension, diabetes, and bipolar disorder presents with disabling impotence.
Which of the following drugs that he might be using is not associated with sexual dysfunction?
E. All of the listed drugs except α1 -blockers are associated with erectile dysfunction. Parasympathetic activity during arousal triggers the release of nitric oxide, which increases the levels of the intracellular cyclic guanosine monophosphate (cGMP). Increases in cGMP cause penile vascular and trabecular smooth muscle relaxation, leading to increase in blood flow. The rapid filling of the cavernosal spaces compresses venules leading to reduction in venous outflow. This process effectively raises intra-cavernosal pressure, resulting in erection. α1 adrenergic blockers can enhance erectile function by reducing the sympathetic tone and relaxing trabecular smooth muscle cells. Nearly 25% of cases of erectile dysfunction are related to medication side-effects. Many prescribed drugs, including β-blockers, H2 antagonists, diuretics, antiepileptics, antidepressants, and antiparkinsonian medications, can cause erectile dysfunction. In addition, street drugs such as cannabis, cocaine, alcohol, ecstasy, and opiates can also lead to impotence.
A 40-year-old man with chronic dysthymia also suffers from impotence unrelated to his depression. His GP prescribes him a medication to be used prior to the sexual act, as and when required.
Which of the following describes the most likely mechanism of action of the prescribed drug?
B. The vasodilatation required to bring on erection is mediated by nitric oxide (NO). Nitric oxide enables vascular smooth muscle relaxation via production of a second messenger, called cGMP. Men suffering from erectile dysfunction (ED) may have successful erection if the availability of cGMP is prolonged or increased. This can be achieved by modulating an enzyme called phosphodiesterase (PDE-5). Normally PDE-5 terminates the action of cGMP by converting it into inactive form (GMP). By inhibiting PDE-5, sildenafil lengthens the life of cGMP and helps to achieve erection.
There are nine different types of PDE found in different tissues of the body; for example coronary tissues have the PDE-3 type receptors; PDE-5 receptors are found in platelets and various muscle tissues; and PDE-6 receptors are found in the retina. Sildenafil has some propensity to act on PDE-6, apart from its primary action on PDE-5; this explains defects in colour vision experienced by some patients taking sildenafil. As sildenafil does not produce new cGMP directly, it cannot act as an aphrodisiac. Hence it cannot help patients with reduced arousal due to other causes such as depression.
Click to expand