What are the common problems of gout?🔍🔍🔍

Gout is a very common metabolic disease clinically. Here are some practical facts and frequently asked questions about gout.

1. What is the difference between hyperuricemia and gout?

Hyperuricemia refers to the blood uric acid levels of both men and women are higher than 420 μmol/L twice on different days. In patients with hyperuricemia, urate crystallizes and deposits in the body. It can cause patients to develop gouty arthritis, uric acid nephropathy, and kidney stones called gout. Some researchers now refer to gouty arthritis as gout. In addition, some patients with hyperuricemia have no obvious symptoms such as arthritis for life, which is called asymptomatic hyperuricemia. Subclinical gout can be diagnosed in patients with asymptomatic hyperuricemia if sodium urate crystal deposition and/or gouty bone erosions are found on examination.

2. Are Gout and Hyperuricemia Inherited to Offspring?

The probability of blood uric acid level being inherited is approximately 27 to 41% and the probability of gout being inherited is about 30%. About 20% of gout patients have a family history of it. Environmental factors such as alcohol consumption, overeating and weather are closely related to the occurrence of gout. Environmental factors such as alcohol consumption, overeating and weather are closely related to the occurrence of gout. Acute gouty arthritis has the characteristics of rapid onset. Within hours, patients experience redness, swelling, heat, pain, and dysfunction in affected joints. Midnight or early morning is the more common time of onset. In addition, due to the poor blood supply, low skin temperature, low interstitial fluid pH and high pressure of the foot, the first metatarsophalangeal joint is the first joint of most gout.

3. What is the relationship between high blood pressure and hyperuricemia/gout?

It is generally believed that for every 60 μmol/L increase in blood uric acid in a patient, his relative risk of hypertension will increase by 1.4 times. Blood vessels and kidneys can be damaged by high blood pressure. It will reduce uric acid excretion and increase blood uric acid level. Angiotensin converting enzyme inhibitors (eg, captopril), angiotensin-receptor blockers (eg, irbesartan, except losartan.), β-blockers (eg, metoprolol), and thiazide diuretics (eg, hydrochlorothiazide and indapamide) significantly increase the risk of gout attacks. Patients with hypertension complicated with hyperuricemia or gout should preferably choose antihypertensive drugs that do not affect blood uric acid levels, such as amlodipine and losartan. Atorvastatin is the first choice for patients with hyperuricemia or gout combined with hypercholesterolemia, which can promote the excretion of uric acid by the kidneys. Fenofibrate is the first choice for patients with hyperuricemia or gout with hypertriglyceridemia, which can inhibit uric acid reabsorption.

4. Are people with hyperuricemia or gout more likely to develop diabetes?

For every 60 μmol/L increase in the blood uric acid level of a patient, the risk of new-onset diabetes increased by 17%. Uric acid-lowering treatment can reduce the incidence of diabetes in people with hyperuricemia. Their incidence of cardiovascular and renal complications will also be reduced. In addition, insulin can lead to elevated blood uric acid levels in patients. Therefore, hypoglycemic drugs such as α-glucosidase inhibitors, metformin, SGLT-2 inhibitors and thiazolidinediones will increase insulin levels in patients. Patients with gout who use hypoglycemic drugs should try to avoid using the above drugs.

5. Do patients with asymptomatic hyperuricemia need uric acid-lowering therapy?

Non-drug treatments such as diet adjustment and weight control will be the first choice for patients with asymptomatic hyperuricemia. Treatment guidelines in China and Japan suggest that patients with asymptomatic hyperuricemia should be treated with uric acid-lowering drugs when the blood uric acid level is ≥540 μmol/L. Treatment guidelines in Europe and the United States recommend that patients with asymptomatic hyperuricemia need to start uric acid-lowering drug therapy only when they have chronic kidney disease and cardiovascular risk factors. Among the urate-lowering drugs, allopurinol can cause fatal allergic reactions in patients, benzbromarone can seriously damage the liver function of patients and febuxostat can increase the risk of cardiovascular events in patients.

6. What value should the blood uric acid target value be reduced to in patients with gout?

Studies have pointed out that when the patient's blood uric acid is controlled at <360 μmol/L for a long time, it can dissolve the urate crystals in the patient's body, and reduce the number and volume of crystals. It also prevents the formation of new urate crystals in the body. It is recommended to control the blood uric acid level of all gout patients to <360 μmol/L, and the blood uric acid level of severe gout patients to be controlled to <300 μmol/L. However, it is not recommended to control the patient's blood uric acid level at <180 μmol/L for a long time.

7. Which uric acid-lowering drugs can be used in patients with gout?

Allopurinol, benzbromarone, and febuxostat are the first-line drugs for uric acid-lowering therapy in patients with gout. Allopurinol and febuxostat inhibit uric acid synthesis in patients. Benzbromarone stimulates the excretion of uric acid. Allopurinol and benzbromarone are the first-line uric acid-lowering drugs for patients with asymptomatic hyperuricemia. If the patient's blood uric acid still does not reach the target value after using a sufficient amount and a full course of monotherapy, two uric acid-lowering drugs with different mechanisms of action can be considered in combination.

8. What uric acid-lowering drugs should be used in patients with gout and chronic kidney disease?

For gout patients with chronic kidney disease, uric acid-lowering therapy can inhibit the progression of their chronic kidney disease. Uric acid synthesis inhibitors such as allopurinol and febuxostat will be given priority to gout patients with chronic kidney disease stage 3 or above (glomerular filtration rate <60ml/min).Since the fatality rate of hypersensitivity reaction to allopurinol is as high as 30% and is obviously related to the HLA-B*5801 gene, patients should be tested for their HLA-B*5801 gene before using it. Therefore, febuxostat is especially suitable for gout patients with chronic renal insufficiency.

9. Do patients with gout who taking benzbromarone need to also take sodium bicarbonate?

Although oral administration of sodium bicarbonate has a certain effect on reducing uric acid in patients with gout, the effect on reducing uric acid is limited. In addition, long-term use of sodium bicarbonate can cause water and sodium retention in patients, which can cause and aggravate high blood pressure and induce heart failure. Therefore, patients only need to take sodium bicarbonate if the pH of the morning urine is <6.0.

10. What is the correct way to use colchicine?

Compared with taking large doses of colchicum, the effect of small doses of gout is similar and the side effects will be significantly reduced. When the patient has an acute gout attack, the first dose of colchicine is 1 mg, and then an additional 0.5 mg is given every hour. Until 12 hours later, take 0.5mg once or twice a day. When patients start uric acid-lowering drug therapy, fluctuating blood uric acid levels can easily induce acute gout attacks. Therefore, patients can take colchicine for at least 3 to 6 months to prevent acute gout attacks. The dosage is 0.5 to 1 mg per day.

11. Why are obese people more prone to gout attacks?

Gout is a metabolic disease and many patients with gout will be accompanied by obesity. The daily caloric intake of obese patients will be greater than the daily consumption. Purine synthesis in the body will increase with the increase in calorie intake, and the production of uric acid will also increase. In addition, obesity, especially abdominal obesity, can cause insulin resistance in patients. Insulin resistance can increase blood uric acid levels in the body. Therefore, many gout treatment guidelines recommend that patients with gout control their weight. 

12. Why are patients prone to gout attacks after drinking alcohol?

Some studies have pointed out that liquor and beer can increase the risk of gout attacks in patients, but there is little evidence that red wine increases the risk of gout attacks. Some studies have pointed out that hard alcohol and beer can increase the risk of gout attacks in patients, but there is little evidence that red wine increases the risk of gout attacks. Metabolism of alcohol increases consumption of ATP. Serum lactic acid will increase due to alcohol, thereby reducing uric acid excretion. The purines in alcohol lead to increased uric acid production. These are the reasons why alcohol consumption can increase blood uric acid levels.

13. What vegetables and fruits should patients with gout eat?

Patients with gout should not eat foods with too much sugar. Therefore, fruits with too much sugar such as apples, oranges and grapefruit should not be eaten too much. Plant foods with high purine content such as mushrooms, seaweed and kelp should not be eaten too much. Patients with gout can eat watermelon, coconut, grapes, strawberries, plums and peaches in moderation. Lemons, cherries and olives have certain benefits for patients with gout. It is recommended to eat low-purine foods such as most melons, tubers, root and leafy vegetables.

14. What kind of meat should patients with gout eat?

White meat such as chicken and duck has lower purine content than red meat such as beef and pork. The purine content of animal offal is generally higher than that of meat. Patients with gout should not consume more than 100g of meat per day. Cured or smoked meats are high in purines and sodium, which interfere with the metabolism of uric acid. Patients with gout are not suitable for eating these foods.

15. How much and how should patients with gout drinking water?

Patients with gout but without contraindications such as kidney disease or heart failure are recommended to drink 2 to 3L of water per day. Patients should try to maintain a daily urine output of about 2 L and a urine pH of 6.3 to 6.8. In addition, lemon water can help lower uric acid. It can add 1 to 2 fresh lemon slices to 2 to 3L of water.

16. How can patients with gout exercise?

Vigorous exercise can increase sweating in patients with gout. It reduces blood volume, renal blood flow, and uric acid excretion. It can even induce gout attacks. Low-intensity aerobic exercise such as jogging can reduce gout attacks in patients. Low-intensity aerobic exercise such as jogging can reduce gout attacks in patients. It is recommended that patients perform low-intensity aerobic exercise 4 to 5 times a week, 0.5 to 1 hour each time. In addition, since low temperature can easily induce acute gout attacks in patients, patients should avoid taking cold baths after exercise.

Read More

What are the precautions for using hypnotics?😴😴😴

In today's society, many people suffer from insomnia. Insomnia is the most common sleep disorder clinically. About 10 to 15% of adults meet the criteria for a diagnosis of insomnia. Generally recommended for the treatment of insomnia psychotherapy and drug therapy. For patients with insomnia, medication is generally used on the basis of psychotherapy. Hypnotic drugs are given according to the patient's condition to relieve insomnia symptoms, improve sleep quality and improve the patient's quality of life.

What medications can be used to treat insomnia?

The principles of drug therapy should be individualized, on demand, intermittent and sufficient. The drug treatment guidelines for insomnia are generally recommended as follows: non-benzodiazepine drugs are the first choice. Short and medium-acting benzodiazepines or melatonin receptor agonists are the second choice. Antidepressants with sedative effects are optional only when necessary, but they are especially indicated for insomniacs with depression and/or anxiety. Treatment guidelines do not recommend the use of antipsychotics and antiepileptics as first-line drugs, and they are only applicable to certain special situations and special populations. 

Non-benzodiazepines: These drugs selectively activate the α subunit of the γ-aminobutyric acid receptor A (GABA_A). Their hypnotic effects are similar to those of benzodiazepines. Due to the short half-life of these drugs, their next-day residual effects are greatly reduced. They generally do not cause daytime drowsiness in patients and have a lower risk of dependence than benzodiazepines. Therefore, non-benzodiazepines can be safe and effective in the treatment of insomnia, and their long-term use has no significant adverse drug effects. Sudden discontinuation of the drug may cause transient insomnia rebound in patients. Because non-benzodiazepines are less muscle relaxant, they cause a lower risk of falls than benzodiazepines. Therefore, non-benzodiazepines are especially suitable for elderly patients with insomnia. CYP3A4 metabolizes non-benzodiazepines such as eszopiclone, zopiclone and zaleplon. Therefore, CYP3A4 inhibitors such as clarithromycin will inhibit their metabolism. It can increase blood levels of non-benzodiazepine drugs and increase the occurrence of adverse reactions. Inducers of CYP3A4, such as rifampin, lower their blood levels and reduce their efficacy. Co-administration of alcohol or other central depressants with non-benzodiazepines increases the central depressant effect. 

1. Eszopiclone: This is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 1 to 1.5 hours and a half-life of 6 hours. Adults take 1 to 3 mg orally before going to bed. Its common adverse reaction is abnormal taste. Eszopiclone was better tolerated than zopiclone.
2. Zaleplon: It is indicated for the treatment of difficulty falling asleep. It has a peak time of ≤1 hour and a half-life of 0.7 to 1.4 hours. Adults take 5 to 20 mg orally before going to bed. Its common adverse reactions are dizziness and ataxia.
3. Zopiclone: It is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 1.5 to 2 hours and a half-life of 5 hours. Adults take 3.75 to 7.5 mg orally at bedtime. Its common adverse reaction is bitter taste in mouth. 
4. Zolpidem: This is indicated for the treatment of trouble falling asleep or maintaining sleep. It has a peak time of 0.5 to 3 hours and a half-life of 0.7 to 3.5 hours. Adults take 1.75 to 10 mg orally or 6.25 to 12.5 mg sustained-release tablets before going to bed. Its common adverse effects are headache, dizziness and forgetfulness.

Benzodiazepines: These drugs bind nonselectively to GABA_A receptors. They have anxiolytic, sedative, muscle relaxant and anticonvulsant properties. Therefore, this class of drugs has a better effect on patients with anxiety insomnia. Benzodiazepines commonly used in clinical practice include estazolam, flurazepam, quazepam, temazepam and triazolam. Among them, triazolam and temazepam are relatively recommended for the treatment of insomnia. Other commonly used benzodiazepines are alprazolam, diazepam, and lorazepam. These drugs are dependent. Therefore, after long-term use, patients may experience withdrawal symptoms after stopping the drug. Most benzodiazepines are contraindicated in pregnant or lactating women, patients with impaired liver and kidney function, patients with obstructive sleep apnea syndrome, and patients with severe ventilatory impairment. In addition to lorazepam and temazepam, CYP3A4 has a certain ability to metabolize benzodiazepines. Therefore, both CYP3A4 inducers and inhibitors affect their plasma concentrations. CNS depressants and alcohol also enhance the CNS depressant properties of benzodiazepines.

1. Estazolam: It is indicated for the treatment of difficulty falling asleep or maintaining sleep. The adult dosage is 1 to 2 mg orally at bedtime. It has a peak time of 3 hours and a half-life of 10 to 24 hours. Its common adverse effects include dry mouth, hangover and weakness.
2. Flurazepam: It is indicated for the treatment of trouble falling asleep or sleep maintenance. The adult dosage is 15 to 30 mg orally at bedtime. It has a peak time of 1.5 to 4.5 hours and a half-life of 48 to 120 hours. Its common adverse effects include ataxia, dizziness and hangover.
3. Quazepam: It is indicated for the treatment of difficulties falling asleep or maintaining sleep. The adult dose is 7.5 to 15 mg orally at bedtime. It has a peak time of 2 to 3 hours and a half-life of 48 to 120 hours. Its common adverse effects include dizziness, drowsiness, dry mouth, headache and unsteadiness on standing.
4. Temazepam: It is indicated for the treatment of difficulty falling asleep or maintaining sleep. The dosage for adults is 7.5 to 30 mg orally at bedtime. It has a peak time of 1.2 to 1.6 hours and a half-life of 3.5 to 18.4 hours. Its common adverse effects include ataxia and dizziness.
5. Triazolam: It is indicated for the treatment of difficulty falling asleep. The dosage for adults is 0.125 to 0.25 mg orally at bedtime. It has a peak time of 0.2 to 0.5 hours and a half-life of 1.5 to 5.5 hours. Its common adverse effects include amnesia, euphoria, upset stomach and skin tingling.

Melatonin receptor agonists: The sleep-wake cycle is regulated by melatonin. Melatonin can effectively improve symptoms caused by jet lag, delayed sleep phase syndrome, and circadian rhythm sleep disorders. Melatonin receptor agonists can be used as an alternative treatment for patients who cannot tolerate benzodiazepines or who have developed drug dependence. Melatonin and ramelteon tablets are commonly used melatonin receptor agonists.

1. Melatonin: It is indicated for patients who have difficulty falling asleep or maintaining sleep. Adults take 2 mg orally before going to bed. It has a peak time of 0.75 to 3 hours and a half-life of 6 hours. Its common side effects are dizziness, drowsiness and fatigue.
2. Ramelteon: It is indicated for patients who have trouble falling asleep. Adults take 8 mg orally before going to bed. It has a peak time of 0.75 to 1 hour and a half-life of 1 to 2.6 hours. Its common adverse reactions are dizziness, drowsiness and fatigue. It is especially effective and safe for insomniacs with sleep-disordered breathing. CYP1A2 is the main metabolic enzyme of ramelteon. CYP2C and CYP3A4 also metabolize a small amount of it. Therefore, CYP1A2 inhibitors such as ciprofloxacin will increase its plasma concentration and should not be used in combination.

Antidepressants: Serotonin and norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants and other antidepressants are also used to treat insomnia.

Serotonin and norepinephrine reuptake inhibitors (SNRIs): Venlafaxine and duloxetine can be used to treat depression and anxiety to improve insomnia.

Selective serotonin reuptake inhibitors (SSRIs): Fluoxetine, fluvoxamine, paroxetine, sertraline, etc. are commonly used clinical SSRIs. They improve insomnia symptoms in patients by treating depression and anxiety disorders. Among them, fluvoxamine has a sedative effect and is a better choice for insomnia patients.

1. Fluvoxamine: It prevents the degradation of melatonin and increases the concentration of endogenous melatonin. It is the only sedating drug among the SSRIs. The combination of doxepin and it will increase the blood concentration of the two drugs, so the dose should be reduced when used in combination. Its starting dose is 50mg or 100mg taken daily at bedtime. The commonly used effective dose is 100 mg per day.

Tricyclic antidepressants: Amitriptyline and doxepin are commonly used tricyclic antidepressants. However, because of its anticholinergic effects, amitriptyline can cause adverse reactions such as dry mouth and increased heart rate in patients, so it will not be used as the drug of choice for the treatment of insomnia.

1. Amitriptyline: It can treat anxiety and depression patients with insomnia. It has a peak time of 2 to 5 hours and a half-life of 10 to 100 hours. Adults take 10 to 25 mg orally before going to bed. Its common adverse reactions are anticholinergic effects, cardiac damage, excessive sedation, and orthostatic hypotension.
2. Doxepin: Doxepin in small doses (3 to 6 mg orally at bedtime) has a specific antihistamine mechanism. It improves insomnia symptoms in adults and elderly patients with chronic insomnia. It also can treat sleep maintenance disorders. It was clinically well tolerated and had no withdrawal effects. It has become one of the recommended drugs for the treatment of insomnia in recent years. It has a peak time of 1.5 to 4 hours and a half-life of 10 to 50 hours. Its common adverse reactions are drowsiness and headache.

Other antidepressants: Small doses of mirtazapine and trazodone can calm the patient and relieve insomnia symptoms. They are used to treat both insomnia and rebound insomnia after hypnotic drug withdrawal.

1. Mirtazapine: It can relieve symptoms of sleep disorders in depressed patients and treat anxiety and depression with insomnia. It has a peak time of 0.25 to 2 hours and a half-life of 20 to 40 hours. Adults take 3.75 to 15 mg orally at bedtime. Its common adverse effects are anticholinergic effects, appetite and weight gain, and excessive sedation.
2. Trazodone: Although its antidepressant effect is weak, it has strong hypnotic power. It can be used in patients with anxiety and depression with insomnia, sleep disturbance or severe sleep apnea syndrome. It may also be used to treat rebound insomnia after the hypnotic drug is discontinued. It has a peak time of 1 to 2 hours and a half-life of 3 to 14 hours. Adults take 25 to 150 mg orally at bedtime. Its common adverse reactions are dizziness, orthostatic hypotension, and priapism.

Orexin receptor antagonist: Orexin has a refreshing effect, also known as hypocretin.

1. Suvoresan: It is an orexin receptor antagonist. It has been approved in some countries for adults with trouble falling asleep or sleep maintenance disorders. It has a different target than other sleeping pills. Studies have shown that it has good clinical efficacy and tolerability. It has a peak time of 0.5 to 6 hours and a half-life of 9 to 13 hours. Adults take 5 to 20 mg orally before going to bed. Its common adverse reaction is residual sedation.

Non-benzodiazepines such as zolpidem and eszopiclone are generally the first choice for clinical treatment of insomnia. If the first-line drug is ineffective, melatonin receptor agonists, short- to medium-acting benzodiazepines, or orexin receptor antagonists can be replaced. Antidepressants may be added to patients with insomnia who are anxious or depressed.

When should patients use hypnotics?

1. Hypnotics may be taken 5-10 minutes before bedtime when the patient anticipates difficulty falling asleep.
2. If the patient fails to fall asleep 30 minutes after going to bed, hypnotics can be taken immediately.
3. Hypnotics can be taken immediately if the patient cannot fall asleep again after waking up at night and is more than 5 hours away from the expected time of waking up. It recommends using hypnotics with a short half-life.
4. Patients with chronic insomnia were treated intermittently with non-benzodiazepines. It will generally take the hypnotics on selected nights per week rather than on consecutive nights.

Read More