Taking the medicine at the wrong time, the effect is halved?

*It is only for medical professionals to read.
Please refer to the medication time of rheumatism patients! Rheumatic diseases refer to a group of autoimmune diseases that affect bones, joints and surrounding soft tissues
.
In addition to joints, clinically, they often involve organs and tissues such as the heart, lungs, kidneys, and nervous system .

At present, the clinical drugs for treating rheumatic diseases mainly include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, traditional disease-improving anti-rheumatic drugs (DMARDs), anti-osteoporosis drugs, uric acid-lowering drugs, and gastroprotective drugs and so on
.

This article mainly summarizes the medication time of the above therapeutic drugs for reference
.

Chronological pharmacology The physiological changes of the human body such as basal metabolism, body temperature changes, blood sugar content and hormone secretion, etc.
all have biological periodicity and peak and valley values
.

The body's circadian rhythm changes the pharmacokinetics and pharmacodynamics of the drug in the body, resulting in circadian changes in its bioavailability, blood concentration, metabolism and excretion
.

The traditional medication regimen is to divide the whole day's dose into several equal doses.
This equalization method is based on the body's physiological function, pathological changes, and drug action being constant throughout the day and night.
The new medication regimen is based on the rhythmic changes of the body to determine the best medication time and dose, which is generally called chronopharmacology
.

It includes chronological pharmacokinetics (circadian changes in the bioavailability, blood concentration, absorption, metabolism, and excretion of drugs) and chronological pharmacodynamics (the human body’s effects on drugs, including effects (side effects), adverse effects) Reaction and its periodic rhythm changes]
.

Making full use of chronopharmacology can fully mobilize the body's active immunity and anti-disease factors by adapting to changes in human biological rhythms, improving the bioavailability and peak concentration of drugs, reducing and avoiding adverse drug reactions, and reducing dosages
.

Chronological pharmacology and clinical rational use of anti-rheumatic drugs❶ NSAIDs mainly include non-selective NSAIDs (such as ibuprofen, indomethacin, flupiprofen, etc.
); selective NSAIDs (such as celecoxib, etorico) Xi, etc.
)
.

Usually, aspirin is taken at around 7 in the morning (after a meal), which can maintain the blood concentration for 15-17 hours, while taking the medicine at 19:00 can only last for 6-8 hours
.

The bioavailability of the medicine taken in the morning is greater than that of those taken at night, the elimination rate in the body is slow, the half-life is long, and the blood concentration is high, so it is recommended to take it in the morning
.

Indomethacin can be taken at 7 o'clock in the morning to get a higher blood concentration, and the peak time is faster, while the blood concentration of taking indomethacin at 19:00 is low, which is 40% different from taking the medicine at 7 o'clock
.

Therefore, indomethacin is recommended to be taken at 7 o'clock in the morning, the dosage is low, and the adverse reactions are small
.

The chrono-pharmacological characteristics of ibuprofen may be related to the preparation form
.

HALSAS and other studies found that the difference between oral ibuprofen immediate-release preparations at 8 o'clock and 22 o'clock was not statistically significant, while its compressed controlled-release tablets were taken at 22 o'clock, with higher bioavailability and shorter peak time
.

Studies have found that in the treatment of patients with rheumatoid arthritis, flupiprofen twice a day has better analgesic effects than four times a day, and taking flupiprofen at night is more effective in controlling morning stiffness and pain in some patients
.

Because NSAIDs have damaging effects on the mucosa of the entire digestive tract (esophagus, stomach, duodenum, small intestine, and colon), and can easily cause gastrointestinal adverse reactions, postprandial administration is recommended
.

❷ Short-acting glucocorticoid preparations include cortisone and hydrocortisone, with an action time of 8-12h; intermediate-acting preparations include prednisone, prednisolone, and methylprednisolone, with an action time of 12-36h; long-acting The preparations include dexamethasone, betamethasone, etc.
, and the action time is 36-54h
.

Patients with rheumatism usually choose intermediate-acting glucocorticoid preparations
.

The role of hormone drugs is closely related to the circadian rhythm of endogenous hormones
.

Clinical scientific research has shown that the peak of human hormone secretion is at 7-8 in the morning, and the daily dose is administered at 7-8 in the morning or once every other morning to avoid the reflex inhibitory effect of the drug on hormone secretion.
, The inhibition of hypothalamus-pituitary-adrenal cortex is light, and adverse reactions can be reduced
.

According to clinical observations, prednisolone 2.
5 mg administered at the same interval 4 times a day can reduce the endogenous secretion of adrenal cortex hormone by 50%, while administration of 10 mg once in the morning has almost no effect
.

Glucocorticoids can stimulate the secretion of gastric acid and protease, cause gastritis, induce or aggravate the original ulcer, and postprandial administration can reduce the occurrence of related gastrointestinal adverse reactions
.

❸ DMARDs methotrexate, sulfasalazine, leflunomide, azathioprine, hydroxychloroquine, cyclosporine, mycophenolate mofetil, cyclophosphamide, tacrolimus and thalidomide, etc.
, All should be taken at a fixed time each day
.

Methotrexate, cyclosporine, etc.
can be taken before or after meals
.

Sulfasalazine and hydroxychloroquine should be taken with food.
If stomach upset occurs after the medication, taking it 30 minutes after a meal can reduce gastrointestinal reactions
.

Leflunomide is recommended to take the medicine before going to bed
.

Azathioprine can be taken 30 minutes after meals
.

Mycophenolate mofetil and tacrolimus should be taken before meals
.

Cyclophosphamide is also recommended to be administered before meals.
If you have stomach upset, you can also take it with food
.

Thalidomide should be taken at least 1 hour after a meal, or before going to bed
.

Table 1 Medication schedule ❹ Anti-osteoporosis drugs include calcium agents, bisphosphonates such as alendronate sodium and so on
.

The human body's blood calcium level is lowest in the latter half of the night to early morning, so taking calcium supplements before going to bed can make calcium fully absorbed and utilized
.

The mechanism of action of alendronate may be that the strong combination of phosphonic acid groups and calcium ions makes the drug act on the surface of the bone mineralization matrix, further inhibiting the formation of hydroxyapatite crystals and their precursors, thereby affecting the formation The bone is broken and balanced to achieve the purpose of treating osteoporosis
.

In order to avoid its interaction with metal ions in food and reduce its efficacy, it is recommended to take it when you wake up in the morning on an empty stomach
.

❺ Uric acid-lowering drugs such as allopurinol, colchicine, benzbromarone and febuxostat
.

Benzbromarone should be taken after breakfast
.

The medication time is based on the following considerations: benzbromarone can reach the maximum uric acid-lowering effect 8-12 hours after oral administration
.

If breakfast is taken at 8 o'clock, the renal excretion of uric acid will reach a peak around 18 o'clock.
During this period, the patient can ingest enough water to ensure sufficient urine volume to dilute the concentration of uric acid in the original urine and promote uric acid excretion
.

But if benzbromarone is taken at 13:00, the peak of uric acid excretion will appear at around 23:00, which is the time of sleep.
Most people have reduced water intake, decreased urination, concentrated urine, decreased pH, and uric acid.
Retention in the kidneys and urinary system is more prone to deposits and crystals
.

In addition, allopurinol and febuxostat are also recommended to be taken at a fixed time during breakfast.
The former can be taken after meals, and the latter can be taken with or without food
.

Colchicine can also be taken with or without food
.

❻ guard proton pump inhibitors such as stomach, H2 receptor blockers, gastric mucosal protective agents
.

The amount of gastric acid secretion has a certain time rule.
The secretion of gastric acid in the human body slowly rises from noon, to a sharp rise around 20 o'clock, and reaches a peak at 22 o'clock
.

Proton pump inhibitors can inhibit gastric acid secretion, reaching a peak 2-5 hours after taking the medicine.
It is usually taken in the morning on an empty stomach.
If you need to take it twice, take it once at 20 o'clock
.

The gastric mucosal protective agent can be taken on an empty stomach so that the drug can fully act on the gastric mucosa.
Under acidic conditions, the mucin on the gastric mucosal surface complexes to form a protective film
.

References: [1] Guidelines for the diagnosis and treatment of rheumatoid arthritis in China (2018).
[2] Yu Zaoqin, Zhang Chengliang, Wang Youqun, Liu Dong.
Circadian rhythm analgesia for pain [J].
Medical Herald, 2014, 33 (6) ): 771-773.
[3] Guo Ping, Yang Dong.
The specific application and pharmacodynamic effects of chronopharmacology on the time of medication [J].
"Chinese Journal of Clinicians", 2016,44(2):26- 28.
[4] Yuan Gang, He Rongfen.
Chronological pharmacology and clinical rational drug use[J].
China Modern Medicine Application, 2012, 6(3): 73-74.
[5] Huang Qiaocai, He Weilu.
Chronological Pharmacology and The best time of administration［J］.
Strait Pharmacy, 2007,19(5):104-106.
［6］Wang Wenwen.
The relationship between chronopharmacology and clinical rational drug use［J］.
China Health Standard Management CHSM, 6(32 ):91-92.
[7] Expert consensus on the prevention of osteoporosis by alendronate (2019).