Adjuvant pain therapy – what is it?
The most important thing in the treatment of any disease is to eliminate not the symptoms of the disease, but the causes of its development. However, not all diseases require etiotropic therapy, for example, cancer and autoimmune diseases. That is why in medicine and pharmacology there are drugs for the pathophysiological and symptomatic treatment of diseases.
Depending on the intensity of pain, the doctor prescribes patients either narcotic medications or non-steroidal anti-inflammatory drugs. To increase the chances of treatment success, various combinations are used, but often the analgesic effect of the drugs is reduced.
Adjuvant therapy is the treatment of diseases using medications that take into account their symptoms, for example, glucocorticosteroids. These highly effective drugs can affect several symptoms of the disease at once, as well as eliminate possible negative consequences for the body and reduce the level of pain. This helps specialists control and more accurately calculate the dose of pain medications, minimizing side effects.
In the treatment of chronic pain syndrome, a fairly wide range of drugs is used, including steroidal anti-inflammatory drugs and many other medications. Depending on the type of pain, its location and clinical picture, doctors use both anti-inflammatory steroid drugs and painkillers, anticonvulsants, antispasmodics and even antidepressants.
Quite often, steroidal anti-inflammatory drugs are used to treat joints, the list of them is quite wide.
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During pregnancy and lactation
Pregnancy is included in the list of contraindications for several reasons:
- when using reserpine before childbirth, the newborn may experience severe drowsiness, swelling of the nasal mucosa and anorexia;
- Thiazide diuretics (hydrochlorothiazide) of thrombocytopenia in the fetus and unborn newborn child .
In addition, all three active components are capable of passing into breast milk, which can lead to the adverse reactions described above, and hydrochlorothiazide can suppress lactation.
Note!
The description of the drug Co-Amlessa on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Overdose
Supposed symptoms
Headache, drowsiness, dizziness, confusion, extrapyramidal disorders, coma , convulsions, muscle weakness, paresthesia , persistent miosis , water-electrolyte imbalance, tachycardia , marked decrease in blood pressure, myocardial ischemia with angina pectoris and arrhythmia , respiratory depression, oliguria , collapse . From the digestive system: dyspeptic symptoms (nausea, vomiting, diarrhea).
Method of treatment
- in conscious patients, induce vomiting, perform gastric lavage , and prescribe activated carbon ;
- with a pronounced decrease in blood pressure, the patient must take a position where the legs are elevated, as well as use plasma substitutes and correct electrolyte disturbances;
- if necessary, it is possible to use vasoactive agents ;
- for diarrhea, therapy with anticholinergic drugs ;
- seizures are controlled with anticonvulsants , for example, slow intravenous administration of Diazepam ;
- with severe respiratory depression - mechanical ventilation ;
- Due to the prolonged action of reserpine, the patient should be monitored for at least 72 hours.
Contraindications
- Susceptibility to substances included in the drug;
- Angioneurotic edema (Quincke's edema), history, congenital or idiopathic;
- Hepatic encephalopathy and liver disorders;
- Hypokalemia;
- Hypotension;
- Cardiogenic shock;
- Bilateral renal artery stenosis or stenosis of the artery of a single kidney;
- Heart failure, poor hemodynamics after myocardial infarction;
- Pregnancy and its planning period;
- Breastfeeding period;
- Severe renal failure (creatinine clearance <30 ml/min);
- Moderate renal failure (creatinine clearance <60 ml/min);
- The drug is contraindicated in children and patients on hemodialysis.
Pharmacodynamics and pharmacokinetics
Adelfan Esidrex is a combination of 3 antihypertensive components that differ in the point of action, while mutually complementing the antihypertensive effect of each other:
- Reserpine is known as a sympatholytic , capable of leading to a fairly long-term depletion of the catecholamine at the endings of the postganglionic fibers of the sympathetic part of the central nervous system and, as a consequence, disruption of impulse transmission and a decrease in tone in the sympathetic part (without changes in activity in the parasympathetic part). Reserpine is also capable of depleting other neurotransmitters, including serotonin , dopamine , and neuropeptides in both central and peripheral neurons. As a result, there is a decrease in elevated blood pressure and heart rate , and a sedative effect is observed. The therapeutic effect develops slowly and can reach its maximum after 2–3 weeks and persist for a long time.
- Dihydralazine is an arterial vasodilator that reduces the tone of the smooth muscles of centripetal vessels (mostly arterioles, which reduces the severity of orthostatic hypotension and helps to increase cardiac output) and reduces peripheral vascular resistance mainly in the vessels of the heart, brain, internal organs, as well as skin and skeletal muscles. When the antihypertensive effect is not pronounced, the strength of blood flow in the dilated bed generally increases.
- The reflex increase in heart rate due to vasodilation and a decrease in blood pressure is neutralized by the complex influence of dihydralazine and reserpine , which suppress the sympathetic part of the nervous system.
- Hydrochlorothiazide is a thiazide diuretic that acts on the cortical segment of the loop of Henle and the distal renal tubules. Inhibition of the reabsorption of sodium and chlorine ions occurs due to antagonistic mutual influence with transport enzymes, which increases the reabsorption of calcium ions, and also leads to increased secretion and excretion of hydrogen and potassium ions. Due to diuresis caused by thiazides , blood volume, cardiac output and systemic blood pressure first decrease, and there is a possibility of activation of the renin-angiotensin-aldosterone system . Long-term therapy with hydrochlorothiazide leads to the maintenance of the hypotensive effect, probably by reducing the peripheral vascular resistance.
Pharmacokinetics of the absorption process of the active components
- reserpine is absorbed quickly after oral administration, with systemic bioavailability up to 50%;
- absorption of dihydralazine in the human body occurs quickly, entering the bloodstream in the unchanged form of dihydralazine and hydrazone metabolites (up to 10%);
- As a result of oral administration of hydrochlorothiazide, approximately 60–80% is absorbed and gives maximum concentration in the bloodstream after 1.5–3 hours.
Distribution
- the relative steady-state volume of distribution for reserpine ranges from 6.4-1.8 l/kg (average value - 9.1 l/kg), binds to albumin and blood lipoproteins by 96%;
- hydrochlorothiazide can accumulate in erythrocytes (during excretion there can be up to 3–9 times more hydrochlorothiazide in erythrocytes than in the blood), and also bind to plasma proteins by 40–70%; the indicator of the steady-state volume of distribution of the final phase of excretion is 3–6 l/kg.
Metabolism information
- Metabolism of reserpine occurs in the liver and intestines to metabolites - methyl reserpate and trimethoxybenzoic acid ;
- Dihydralazine metabolism is largely carried out along the path of oxidation (to hydrazones ), as well as acetylation;
- the level of metabolism of hydrochlorothiazide is very low - it can only be found in trace amounts in the form of 2-amino-4-chloro-M-benzene disulfonamide .
Hatch Characteristics
- Reserpine elimination has two phases: the half-life of phase I is 4.5 hours; II - 271 hours. Up to 8% of the dose taken is excreted through the kidneys mainly in the form of metabolites, 62% of the unchanged substance is excreted by the intestines;
- T1/2 for unchanged dihydralazine is 4 hours: approximately 46% of the orally administered dose is excreted in the form of metabolites by the intestines, 0.5% of the dose is unchanged substance that is excreted in the urine;
- elimination of hydrochlorothiazide is also two-phase: the half-life of the initial phase is 2 hours, the final phase is 10 hours. 50–75% of the dose taken orally is removed from the body in the urine.
Changes in pharmacokinetics in certain groups of patients
- for elderly patients, as well as patients with functional renal impairment: it is recommended to reduce the average therapeutic dose due to a significant decrease in the clearance of hydrochlorothiazide and an increase in its concentration in the blood;
- impaired renal and liver function can lead to the accumulation of dihydralazine ;
- in case of renal failure, the process of excretion of reserpine , which is compensated by increased excretion through the intestines. However, in order to avoid the accumulation of reserpine, a single dose is adjusted or the time between doses is increased, monitoring the dynamics of blood pressure and tolerability.
Side effects
In general, the components in Adelfan Esidrex tablets are contained in smaller quantities than those used individually for arterial hypertension , but there is a possibility of adverse events occurring under the influence of each of the active components of the drug.
- Therapy with Adelfan Esidrex can lead to the following digestive system symptoms: diarrhea, dry mouth, increased secretion of gastric juice, increased salivation, nausea and vomiting, increased appetite, pancreatitis , ulcer formation, gastrointestinal bleeding.
- Liver disorders: Less than 1% of subjects experienced jaundice , liver dysfunction, or hepatitis .
- CVS: developing sinus bradycardia , tachycardia , angina , heart failure, swelling, arrhythmias , chest pain, orthostatic hypotension , fainting, hot flashes , cerebral circulatory disorders.
- Respiratory organs: swelling of the nasal mucosa or lungs, shortness of breath, nosebleeds, pneumonitis .
- Central nervous system: depression , dizziness, headache, irritability, increased anxiety, nightmares, fatigue, agitation, anorexia , extrapyramidal disorders (for example: parkinsonism ), peripheral neuritis , paresthesia , impaired attention and orientation, possible stupor , as well as cerebral edema .
- Sense organs: blurred vision, lacrimation, conjunctival hyperemia; hearing impairment.
- Genitourinary system: disturbances of potency and the ejaculation process, development of dysuria , glomerulonephritis .
- Endocrine system and metabolism: weight gain, increased secretion of prolactin , swelling or spontaneous leakage of milk from the mammary glands, gynecomastia .
- Disturbances of water-electrolyte balance: hyperuricemia , hypokalemia , hyponatremia , hypomagnesemia , hypercalcemia , increased concentration of lipids in the blood, glycosuria , hypochloremic alkalosis .
- Epidermis: urticaria , eczema , itching, skin rash, photosensitivity , necrotizing vasculitis , Lyell's syndrome , lupus-like syndrome .
- Other reactions: arthralgia , decreased libido, fever , anemia , thrombocytopenia , leukopenia , agranulocytosis , purpura , hypersensitivity reactions.
Analogs
Level 4 ATC code matches:
Brinerdine
Trirezide K
Normatens
Adelfan
There is no complete coincidence in the composition of the active substances, but there are analogues according to the ATC code, where the active substance is the same - reserpine and the drugs are supplemented with the active dihydroergocristine and clopamide :
- Kristepin (producer Czech Republic);
- Normatens (manufacturer: Poland/Germany).
