MEDICINAL PLANTS - O.O. Annamuhammedova - 2014

I. Theoretical Part

Topic: Physiological Effects of Herbal Medicinal Products

Objective: to familiarize students with the Physiological Effects of plant-derived medicines on body systems

Outline

1. Plant-derived medicines affecting The Nervous system.

2. Plant-derived medicines affecting respiratory function.

3. Plant-derived medicines affecting The Cardiovascular system.

4. Plant-derived medicines regulating Digestive System function.

5. Plant-derived medicines affecting the Urinary System.

6. Plant-derived medicines as regulators of the hematopoietic system.

Key terms and concepts of the topic: local anesthetics, cholinergic synapses, cholinergic agents, adrenergic agents, analeptics, narcotic and non-narcotic analgesics, M-cholinomimetics (muscarinic), N-cholinomimetics (nicotinic), M-cholinoblockers (atropine group), antitussives, bronchodilators.

Questions for independent preparation:

1. Plant-derived medicines affecting the hormonal system.

2. Plant-derived medicines used for Skin conditions. Bactericidal action.

3. Plant-derived medicines affecting The Musculoskeletal System.

QUESTIONS FOR SELF-analysis and self-testing:

1. MECHANISM OF ACTION of local anesthetics.

2. Effects of medicinal products acting in the area of efferent nerves.

3. Mechanism of the reflex action of expectorants.

4. Effects of cardiac Glycosides on the cardiovascular system.

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1. a) Local anesthetics are a group of substances that reduce the sensitivity of nerve endings upon direct contact with them.

To understand The Mechanism of action of substances that affect the nervous system, one should recall the functioning of Neurons in the nervous system. A nerve Cell consists of a cell body (soma), several dendrites that conduct signals from receptors to The Cell body, and an axon that conducts impulses away from the cell body.

An essential function of the cell is the generation of an Action Potential, the conduction of excitation along nerve fibers, and its transmission to another nerve cell. At rest, a nerve cell maintains a Resting Potential, whereas in an excited state, it generates an action potential. One of the purposes of METABOLISM in a nerve cell is to establish an asymmetric distribution of ions across The cell membrane, which determines this potential. The concentration of ions, primarily Na⁺ and K⁺, is crucial for the GENERATION AND PROPAGATION of a Nerve Impulse along the axon. Because the membrane effectively insulates the cell interior, the concentration and Chemical composition of substances inside differ significantly from those in the extracellular fluid. The extracellular fluid is rich in Na⁺ and Cl^- ions, whereas the cell interior contains high levels of K⁺ and negatively charged organic ions. No matter how robust the cell membrane is, owing to its semi-permeability, it cannot entirely prevent the passive diffusion of K⁺ out of the cell, as potassium ions penetrate membrane pores most readily. Consequently, the net internal charge of the cell decreases, while the external charge increases. A potential difference (70 мВ) arises between the cell and its surrounding environment. However, free ion penetration does not lead to complete concentration equalization because, for instance, Cl^- ions are retained outside the cell by sodium, which cannot freely cross inward, while the efflux of K⁺ is restrained by large organic anions. This state is known as the resting state, and the established potential is the resting potential.

Nerve cell excitation, triggered by electrical or chemical stimuli that lower the cell's resting potential, leads to The Development of an action potential.

The underlying mechanism is as follows: the permeability of the cell membrane changes abruptly as specialized pathways, known as sodium channels, open. A rush of positively charged Na⁺ ions enters the cell via passive transport down their concentration gradient and Electrochemical Potential. The electrical environment inside the cell alters dramatically. As a result, the membrane depolarizes and its charge is reversed; the sodium channels then close while potassium channels open, allowing an outward flow of K⁺ ions that restores a negative internal environment. Thus, the resting state is restored. These Ion Channels are voltage-gated, and their opening in adjacent Cells is triggered by the Propagation of Excitation.

Nerve fibers, although they transmit electrical impulses over considerable distances, bear only a very distant resemblance to electrical wires. While the Cytoplasm filling neuronal processes is capable of conducting electric current, these processes are extremely thin and therefore possess immense electrical resistance. A nerve fiber 1 m long and 1 µm in diameter has a resistance equivalent to that of a copper wire 1 mm in diameter and 40,000 times the distance from the Earth to the Moon. Consequently, nerve fibers cannot function as simple electrical conductors. Instead, they generate a nerve impulse along every segment of their membrane—a process comparable to a flame traveling along a fuse. This represents one of the two mechanisms by which myelinated fibers conduct impulses.

Once a nerve impulse generated in the neuron's soma reaches the axon terminal, what happens next? How does it cross over to the next nerve cell? The junction where the axon of one neuron meets the dendrites of another is called a synapse. The axon branches into tiny twigs ending in flattened synaptic knobs, separated from the target by a synaptic cleft. In addition to these, there are dendrodendritic, axo-axonal, axosomatic, and dendrosomatic synapses.

Recall that the propagation of excitation must begin with the opening of channels situated from the inside toward the presynaptic cleft; directly opposite the synaptic knobs, sodium channels open from the outside.

To unlock these cellular gates, the nervous system uses a set of "keys" known as Neurotransmitters. There are some 20 to 30 types of them, with acetylcholine, norepinephrine, and other catecholamines being the most widespread. All of these are packaged inside vesicles. Within the synaptic cleft, these vesicles rupture, and their empty shells are subsequently recycled. Ca²⁺ ions play a crucial role in this process. Because sensitive structures are phylogenetically older than motor structures, parabiosis occurs earlier and develops more profoundly in them.

The local anesthetic cation binds to sodium-potassium channels, competing with Ca²⁺. At THE MOLECULAR LEVEL, an electron-donating interaction takes place between the anesthetic molecules and the anionic complexes of the membrane, with the carbonyl group playing a decisive role in the anesthetic-receptor complex.

Thus, local anesthetics suppress the excitation of nerve fiber membranes, reduce the amplitude of the action potential, and elevate the membrane depolarization threshold.

Cocaine is the prototype of local anesthetics. For medical purposes, cocaine is extracted from coca leaves because chemical synthesis is exceedingly complex. Early travelers to South America observed that the indigenous population had a longstanding tradition of chewing these leaves to suppress pain and hunger and to induce vitality. It was not until 1859 that Niemann and Wöhler isolated the alkaloid cocaine from coca leaves. Over time, numerous physicians investigated its physiological properties. The elucidation of cocaine's chemical Structure enabled Einhorn to synthesize the well-known novocaine in 1905. Even in small doses, cocaine causes a total loss of all types of sensation. It acts as a vasoconstrictor, causing tissue blanching; side effects include dryness of the mucous membranes, cornea, and conjunctiva. Up to 95% of the drug is degraded in the Liver within an hour, with the remainder excreted by the Kidneys. Upon entering the bloodstream, it stimulates the nervous system and induces euphoria, which is subsequently followed by depression. Death results from paralysis of the respiratory center, making it a highly toxic substance. The Discovery of the anesthesiophorous group led to the development of simpler analogs—esters of p-aminobenzoic acid—which exhibit lower toxicity and the distinct advantage of not causing dependence.

b) nerve endings that transmit information as signals toward nerve centers are called afferent, whereas those conducting impulses from nerve centers to effector Organs are called efferent.

Efferent nerves are subdivided into somatic nerves, which innervate skeletal Muscles, and autonomic nerves.

With the advancement of neurotransmitter research, a Functional Classification of efferent nerves emerged into cholinergic and adrenergic types, categorized According to the specific mediator that transmits the nerve impulse.

Principles of cholinergic synapse function. Acetylcholine is synthesized from Choline and acetic acid. This process is reversible; once Acetylcholine is released from the vesicles, it is broken down into its constituent derivatives. Storage within vesicles protects acetylcholine from degradation by the enzyme acetylcholinesterase. Its release alters membrane permeability to Na⁺, triggering depolarization in Nerve Cells and generating an action potential. In Muscle or secretory cells, the action potential prompts the release of Ca²⁺, resulting in contraction or secretion.

Cholinergic receptors across different cells are not identical. Research has shown that cholinergic receptors in certain organs are activated not only by acetylcholine, but also by muscarinic toxins from the fly agaric mushroom, while in other organs they respond to small doses of the tobacco alkaloid nicotine.

Substances that act directly on cholinergic synapses include choline esters, whereas indirect action involves the inhibition of the enzyme cholinesterase.

When these receptors are blocked, the neurotransmitter is not degraded, and its physiological effect is prolonged. Such compounds are termed anticholinesterase agents. They include salts of the alkaloid physostigmine (eserine), extracted from the calabar bean, which comes from the African plant Physostigma venenosum.

Anticholinesterase agents increase the tone of smooth muscle in the Bronchi, Stomach, and intestines, as well as the secretion of salivary and Sweat Glands. Their visible effects include miosis (pupillary constriction) and bradycardia (resulting from vagal center stimulation).

Nicotinic (N-) cholinomimetics (nicotine-like agents). In addition to nicotine, this group includes the alkaloid lobeline, isolated from the plant Lobelia inflata, and cytisine, found in the seeds of laburnum and broom grasses.

A key effect of these agents is The stimulation of the respiratory center, leading to faster, deeper breathing and increased pulmonary ventilation—properties that characterize them as respiratory analeptics. Simultaneously, by acting on the Adrenal Glands, they enhance the release of adrenaline and elevate Blood pressure. However, in high doses, they block N-cholinergic receptors. They stimulate the nervous system, provoke vomiting, induce convulsions, and cause bradycardia.

These exact symptoms are observed in individuals who are just beginning to smoke. With regular smoking, however, the body adapts to nicotine, and the predominant effects shift toward N-cholinergic receptor activation, respiratory stimulation, and elevated blood pressure. Because nicotine acts on the Brain, users experience a subjective sense of heightened focus and productivity, alongside a temporary suppression of hunger and thirst and reduced drowsiness.

Long-term smoking leads to psychological dependence, meaning that quitting requires a conscious act of willpower. Furthermore, it contributes to Hypertension, atherosclerosis, Chronic Bronchitis, and peptic ulcers. N-cholinomimetics are clinically utilized in cases of Carbon monoxide poisoning, brain trauma, and Neonatal Asphyxia.

Muscarinic (M-) cholinomimetics (muscarine-like agents) are substances that mimic the effects of muscarine. Among them is pilocarpine hydrochloride, a salt of the alkaloid pilocarpine found in the leaves of the South American plant Pilocarpus jaborandi. Even in small doses, pilocarpine sharply increases The activity of secretory cells, enhancing The production of bronchial mucus and stimulating lacrimation, salivation, sweating, and digestive juice secretion. Over a 3–4 hour period of drug action, up to 3 liters of sweat may be produced, bringing the total fluid output of the body to 5–6 liters. This medication is used in the Treatment of uremia (reduced urine output). By inducing the contraction of the ciliary muscle and the sphincter pupillae, pilocarpine reduces intraocular pressure and relieves accommodation spasms (by relaxing the muscle that alters the shape of the lens, focusing Vision on the far point).

M-cholinomimetics (the atropine group). This group includes natural substances, specifically Alkaloids such as hyoscyamine and scopolamine (extracted from thornapple), as well as platyphylline. A characteristic feature of atropine is its ability to reduce the tone of smooth muscles, particularly those in a resting state.

It dilates the bronchi, which is beneficial in Bronchial Asthma. Atropine decreases the tone of the Urinary Bladder, Gallbladder, and Bile ducts; this property is utilized in treating renal and biliary colic. Additionally, it causes relaxation of the ciliary muscle, pupil dilation, and an increase in intraocular pressure. In toxic doses, it induces acute psychosis and severe excitation of the nervous system.

Mechanisms of action in adrenergic synapses. The neurotransmitter is stored in synaptic vesicles and released into the synaptic cleft upon the arrival of a nerve impulse. Unlike cholinergic synapses, these synapses doann't contain a hydrolyzing enzyme. Impulse transmission is completed by the reuptake of the neurotransmitter, where it is repackaged into vesicles.

Drugs acting on adrenergic synapses. Direct action occurs through the stimulation of adrenergic receptors by norepinephrine and other catecholamines, which facilitate the release of norepinephrine.

Adrenaline leads to an increase in blood pressure, stimulates cardiac Blood Vessels, and enhances Glycogenolysis.

An important indirect-acting adrenomimetic is ephedrine. It is used in the form of ephedrine alkaloid hydrochloride, which is found in Ephedra equisetina. It has a prolonged duration of action (4–6 hours), causes vasoconstriction and bronchodilation, and, by penetrating the blood-brain barrier, exhibits psychostimulatory effects.

Substances that block adrenoceptors and disrupt the synthesis, storage, and release of norepinephrine are called antiadrenergic agents.

These include, in particular, the ergot alkaloid (ergotamine).

Reserpine is an alkaloid derived from Rauwolfia serpentina, which grows in Southeast Asia and India. It depletes the stores of the neurotransmitter in the vesicles by disrupting the permeability of their membranes to its precursor, dopamine.

Agents acting on the Central Nervous System. Among them is a large group of drugs known as analgesics ("an" – meaning negation, "algos" – pain). These are substances that reduce or eliminate pain. They are classified into narcotic and non-narcotic analgesics.

Among narcotic analgesics, morphine holds a special place. Morphine is an alkaloid derived from the opium poppy and possesses potent pain-relieving properties.

The effects of morphine depend on the dose and manifest in two phases: 1) euphoria (from the Greek eu – good, phoria – feeling). During this phase, unpleasant physical sensations and distressing memories vanish, and mental activity increases. Although the perception of the pain signal remains, the subjective evaluation changes: "I feel the pain, but I pay no attention to it." This effect is associated with the enhancement of inhibitory influences on afferent impulses within subcortical centers.

In the body, particularly in specific structures of the central nervous system, there are so-called opioid receptors that bind to morphine. The endogenous ligands for these receptors are brain Peptides known as enkephalins and endorphins. It has been established that they act as potent natural analgesics. Enkephalins are released during acupuncture and under The Influence of various emotional states.

There is a strong structural similarity between morphine and enkephalins. Therefore, one of the causes of dependency and withdrawal symptoms may be a reduction in enkephalin levels within the brain. Through a negative feedback mechanism, enkephalins, acting as natural neurotransmitters, disappear from the synaptic cleft. Consequently, upon the cessation of morphine use, the central nervous system experiences a deficit of its own analgesics. The symptoms of the condition (morphinism) subside once the natural neurotransmitter levels are restored. Morphine is indicated for severe pain and is used for anesthesia in inoperable oncological tumors.

Heroin is a synthetic analog obtained by the Acetylation of morphine and exhibits twice the analgesic potency. Acute morphine poisoning manifests as deep coma, respiratory depression, lowered blood pressure, bradycardia, and anuria. A characteristic sign of morphine and analog use is marked miosis (pinpoint pupils).

First aid: gastric lavage with 0.05% KMnO4 (which oxidizes morphine). Administration of respiratory stimulants (oxygen inhalation, artificial pulmonary ventilation). Rubbing and cold douches act as reflex stimulants.

Morphine is a traditional antidyspeptic agent; it decreases the motility of The Stomach and duodenum and reduces bile secretion.

Non-narcotic analgesics include antipyretics and anti-inflammatory drugs, specifically salicylic acid derivatives. Unlike narcotic analgesics, they are more effective when inflammation is present. Therefore, they are particularly useful for toothaches, joint pain, and headaches. They do not cause euphoria or alterations in mental state, though they exert a mild depressant effect on the CNS. Their antipyretic action is due to their influence on thermoregulation processes during fever.

Salicylates accelerate The excretion of uric acid, exhibit choleretic properties, reduce blood clotting, and suppress plasma fibrinolytic activity. Consequently, they are contraindicated in patients with hypocoagulation, bleeding disorders, gastritis, PEPTIC ULCER DISEASE, bronchial asthma, and other allergic conditions.

Agents that reduce central nervous system excitation. This group includes tranquilizers. Herbal tranquilizers possess a general sedative effect, such as preparations derived from valerian ROOT and rhizomes, or motherwort. The Site of Action for valerian is the sensitive elements of the activating system in the Diencephalon. As a result, the excitation threshold of neurons is raised, and afferent impulses reaching the Cerebral Cortex are restricted. Emotional and motor calmness ensues. Additionally, valerian is capable of dilating cerebral and coronary vessels, leading to improved metabolism within them.

Analeptic agents. Analeptics (from the Greek analepsis – recovery) are drugs that, in therapeutic doses, restore the function of vital centers in the Medulla Oblongata—specifically the respiratory and vasomotor centers. They also exert a stimulating effect on the cerebral cortex, subcortical centers, and the Spinal Cord.

A crucial property of these agents is their stimulatory effect, which becomes particularly pronounced against the Background of life-threatening CNS depression. For this reason, they are also referred to as revitalizing agents. Physiologically, they act as antagonists to general anesthetics, narcotic analgesics, hypnotics, and alcohol, possessing arousal properties. However, as antinarcotic agents, analeptics are effective only in large doses that significantly exceed therapeutic levels. Therefore, they are utilized in situations such as drug overdoses, in doses sufficient solely to restore Respiration and Blood Circulation.

Herbal agents of this type include the caffeine group of alkaloids (caffeine, theobromine, theophylline), which are found in tea leaves, coffee beans, cocoa pods, and kola nuts. They have been used since ancient times to prepare stimulating beverages. The primary source for the manufacture of medicinal preparations is plant raw material waste.

They are purine derivatives closely related to certain products of its metabolism. This accounts for the wide therapeutic breadth of their action, characterized by low toxicity and minimal accumulation in the body.

Caffeine possesses the most pronounced arousal effect and acts as a CNS stimulant antagonist. It has long been known that tea, coffee, and other caffeine-containing beverages alleviate sleepiness and fatigue, enhance mental performance, and induce a sense of freshness and vigor. Other related compounds exhibit slightly lesser effects. Interestingly, all of them display a diuretic effect associated with the reduced reabsorption of electrolytes and Water in the renal tubules. At the biochemical level, their mechanism of action involves the activation of glycogenolysis.

Sedatives (from Lat. sedare — to calm) belong to a group of agents that depress the central nervous system. By enhancing inhibitory processes or suppressing excitation, drugs of this group exert a regulatory influence on central nervous system Functions. In terms of potency, sedatives are significantly inferior to neuroleptics and tranquilizers. They do not cause lethargy, drowsiness, or dependency, and are widely used for therapeutic purposes. Sedatives facilitate the effects of hypnotics, non-narcotic analgesics, and tranquilizers, and help induce Sleep, particularly in neurotic disorders.

These include preparations of valerian (Valeriana officinalis), motherwort (Leonurus), bogbean (Menyanthes trifoliata), passionflower, peony, and various combination products based on them.

Adaptogens are agents, predominantly of plant origin, that exert a general tonic effect on major bodily functions and systems while increasing the body's resistance to adverse environmental factors. Typical representatives of this group include tinctures and fluid extracts of lemongrass, ginseng, high zammanicha, rhodiola rosea (golden root), eleutherococcus, leuzea, and echinacea, which have long been widely used in traditional medicine.

Adaptogens enhance physical and mental performance, help reduce fatigue and appetite disturbances, and increase the body's resilience to harmful factors, high ambient temperatures, hypothermia, intoxications by industrial poisons, ionizing radiation, and more. They improve blood circulation and possess cardioprotective and hepatoprotective properties.

2. Respiratory stimulants (reflex, direct, and mixed-action stimulants).

One of the most life-threatening situations is a sudden and sharp depression or cessation of respiration. This may be caused by poisoning with certain substances, particularly in the event of a drug overdose. Stimulation of the respiratory center can be induced reflexively by acting on Skin Receptors, such as through massage or cold-water dousing. Plant-based preparations—specifically cytiton, lobeline, Terpenes, and aromatic oils—are used for this purpose. However, it should be emphasized that excessive doses of these substances can actually cause respiratory arrest. If these measures prove insufficient, mixed-action stimulants are employed, which affect the respiratory center via chemoreceptors. In particularly severe cases, direct-acting stimulants are used, such as strychnine or caffeine preparations.

Agents affecting the Functions of the respiratory organs. This category includes agents that influence the tone of the respiratory center, the lumen of the Upper Respiratory Tract, alveolar gas exchange, and the condition of the respiratory mucous membranes.

The function of external respiration is primarily associated with maintaining the Homeostasis of the internal environment of the body, a key parameter of which is the pH level. It characterizes the acid-base balance and gas COMPOSITION OF THE blood. Specifically, the functional state of the respiratory center depends on blood hydrogen ion concentration and neuro-reflex regulation.

The bronchial lumen and the secretory activity of the glandular apparatus (whose glands secrete fluids containing Proteolytic Enzymes) are regulated by the Autonomic nervous system. An increase in sympathetic tone elevates the respiratory rate and causes bronchodilation. The parasympathetic (vagus) nerve causes a slowing of respiration, a decrease in the bronchiolar lumen, and increased glandular secretion.

Expectorants. Under normal physiological conditions, the upper respiratory tract is continuously cleared of foreign elements through the constant action of the ciliated epithelium and the peristalsis of the bronchioles.

During respiratory inflammation, secretions accumulate, and the cleansing process is impaired. Agents that assist in such cases act through various mechanisms:

a) Agents with a direct effect on the inflammatory process, administered via the respiratory tract. These include Essential Oils and enzymes (Chymotrypsin). They liquefy secretions, exhibit bactericidal action, and stimulate peristalsis by acting on receptors.

b) Agents with a reflex effect on bronchial glandular secretion and peristalsis: ipecac root, marshmallow, bugloss, thyme, and thermopsis.

Ipecac root extract can serve as a model preparation for understanding the mechanism of reflex expectorant action. Its active ingredient is the alkaloid emetin. Upon entering the stomach, emetin irritates the receptors of the gastric mucosa, from which impulses travel via sensory fibers to the nuclei of the Vagus nerve. The excitation is then transmitted along efferent pathways (secretory and motor) to the glands and smooth Muscles of the bronchioles. As a result, secretion and peristalsis are enhanced, facilitating the liquefaction of mucus and its upward propulsion. When a large dose is administered, the reflex arc closes at the gastrointestinal mucosa, triggering the mechanisms of the vomiting act.

c) Agents that stimulate the secretory function of the mucous membrane during the elimination of secretions via the Lungs.

Antitussives. When sputum reaches the bronchial bifurcation during coughing, a cough reflex is triggered. Sometimes the cough becomes prolonged and distressing. Furthermore, this leads to increased intrathoracic pressure and exhaustion of the cough center. Antitussives can reduce the frequency or intensity of coughing fits. In such cases, narcotic analgesics (alkaloids) or non-narcotic agents like libexin are used.

Bronchodilators. These are particularly essential during asthma attacks. Bronchial asthma is characterized by an imbalance in the Divisions of the autonomic nervous system—specifically, a decrease in sympathetic tone and an increase in the tone of nerves innervating the circular muscle layer and Glands of the bronchi. The result is a narrowing of the bronchiolar lumen. In such cases, anticholinergics or adrenomimetics are used, which increase the tone of the medulla oblongata; these include isoprenaline and ephedrine preparations. Anticholinergics include atropine, platyphylline, and scopolamine preparations. Antispasmodics include papaverine, theophylline, and theobromine preparations.

3. Agents affecting the cardiovascular system. These include agents that lower or raise blood pressure (antihypertensives, hypertensives) and agents that influence cardiac function (cardiotonics), notably cardiac glycosides. THE SPECTRUM OF action of cardiac glycosides is quite broad.

In the action of glycosides on the cardiovascular system, The most significant is the systolic effect, which manifests as an increase in the force and speed of cardiac contractions. Under their influence during systole, the absolute force of ventricular and atrial contractions increases, blood ejection becomes more complete, and stroke volume and Cardiac Output rise. This is the so-called cardiotonic effect, which results from the direct action of glycosides combined with a reflex action (via the carotid sinus and aortic arch zones) on the vagus nerve (n. Vagus).

Mechanism of action:

1. Myocardial contraction — ionized Ca²⁺ plays one of the primary roles. Glycosides promote its release in the myocardium and delay its inactivation.

2. They impede the return of K⁺ into myocardial cells and the efflux of Na⁺; by blocking The sulfhydryl groups of the Na⁺-K⁺-ATPase enzyme, they disrupt the function of the ion pump. This creates favorable conditions for the enhanced release of Ca²⁺ from its bound state. Consequently, an increase in myocardial contractility is observed under the influence of glycosides.

3. The realization of the systolic (positive inotropic) effect involves the influence of cardiac glycosides on myocardial Protein metabolism. The levels of actinomyosin and other Proteins are elevated.

An important property of glycosides is their ability to prolong diastole. The Heart relaxes more quickly, diastolic blood volume increases, and more favorable conditions are created for the rest of the heart muscle. Consequently, on the one hand, slowed heart contractions and an increased blood volume filling the heart chambers during diastole, and on the other hand, their more complete emptying during systole, lead to an increase in stroke volume and cardiac output.

Bradycardia (slowing of the heart rate) is caused by the inhibition of impulse conduction through the cardiac conduction system; stimulation of the carotid sinus receptors leads to an increased tone of the vagus nerve center (n. vagi). Glycosides increase the sensitivity of the myocardium in the conduction nodes to acetylcholine. Overdose of glycosides disrupts "subordination" within the cardiac conduction system, which in turn can lead to asystole.

Cardiac glycosides have a very peculiar effect on blood pressure. In circulatory decompensation and low blood pressure, cardiac glycosides help normalize it due to their systolic effect. In hypertension, they lower blood pressure through the stimulation of the vasomotor center. At normal pressure, glycosides do not alter it.

BIOCHEMICAL BASIS OF the mechanism of action of cardiac glycosides, especially in heart failure. In heart failure, when Glycogen and ATP levels are reduced, and the retention of lactic acid in the myocardium is replaced by its release into the blood, glycosides increase glycogen and ATP levels and restore lactate levels.

Increased diuresis (diuretic effect) is enhanced by improved blood circulation. Due to a direct effect on the renal parenchyma, the reabsorption of salts is inhibited.

Symptoms of cardiac glycoside overdose.

1. Cardiac symptoms (90% of cases): bradycardia, followed by tachycardia, and arrhythmias up to atrioventricular block.

2. Gastrointestinal symptoms (50%): loss of appetite, nausea, vomiting, abdominal pain.

3. Visual impairments (95%): objects appear yellowish or greenish, magnified or reduced in size; rings or spheres appear before the eyes (due to retrobulbar optic neuritis).

4. Neuropsychiatric symptoms: headache, insomnia, confusion.

5. Altered renal function: decreased daily urine output.

In terms of their pharmacological properties, glycosides are similar either to digitalis or to strophanthus. In order of decreasing digitalis-like properties and increasing strophanthus-like properties:

digitoxin → digoxin → acedoxin → celanide → pheasant's eye glycosides → convallatoxin.

Elevated blood pressure—arterial hypertension—is one of the leading causes of mortality and disability due to its high prevalence. Arterial hypertension is diagnosed in 10–30% of the adult population in many industrialized countries, and in more than 40% of elderly and senile individuals. Arterial hypertension is a major risk factor for stroke, myocardial infarction, heart failure, and renal failure.

Antihypertensive agents cause a decrease in blood pressure (BP). The level of BP depends on the stroke volume and cardiac output, which in turn depend on the strength of cardiac contractions and venous return; peripheral resistance, determined by the lumen of capillaries and arterioles; blood viscosity; electrolyte balance; and the elasticity of arterial walls.

Humoral factors with vasodilating and vasoconstricting effects play a significant role in BP regulation. A correlation has been established between blood pressure levels and age, gender, racial and ethnic characteristics, heredity, metabolic features, psychosocial factors, and physical activity.

As noted above, one of the causes of arterial hypertension is the narrowing of the lumen of capillaries and arterioles. This occurs during the sclerosis of blood vessels, specifically through the deposition of Cholesterol "plaques" in the vessel walls. The development of atherosclerosis is based on Lipid Metabolism disorders, primarily involving cholesterol. In Blood Plasma, Lipids form complexes with proteins—Lipoproteins—which can penetrate the inner lining of the arterial wall. The following types of lipoproteins are distinguished:

1) chylomicrons, which transport dietary triglycerides to sites of utilization;

2) very low-density lipoproteins (VLDL, or pre-β-lipoproteins), which contain predominantly endogenous triglycerides;

3) intermediate-density lipoproteins (IDL), which contain roughly equal amounts of triglycerides and cholesterol;

4) low-density lipoproteins (LDL, or β-lipoproteins), which contain a significant amount of cholesterol;

5) high-density lipoproteins (HDL, or α-lipoproteins), which contain more protein (about 50%) and less phospholipid (about 30%). The density of lipoproteins depends on their lipid component: the higher the lipid content, the lower the density.

Agents that lower triglyceride levels enhance metabolic processes in the liver, including the biotransformation of cholesterol and triglycerides. These agents also reduce the release of free Fatty acids from adipose depots, potentiate the action of anticoagulants, and promote the excretion of uric acid.

VLDL, IDL, and LDL have an atherogenic effect due to their high triglyceride and cholesterol content. When interacting with hepatic and vascular lipoprotein receptors, cholesterol is cleaved from these atherogenic lipoproteins. As complex esters, it deposits in the inner lining of blood vessels, thereby promoting atherogenesis. Conversely, elevated levels of HDL (a-lipoproteins) prevent atherosclerotic vascular lesions by extracting cholesterol from arterial walls. An essential component of lipoproteins is apolipoproteins, which preserve lipoprotein structure and ensure their interaction with cell Membrane Receptors. The primary target for atherogenic lipids is the vascular wall. Therefore, agents for atherosclerosis Prevention (hypolipidemic drugs) must protect the vascular wall, acting as angioprotectors. Angioprotectors are agents that improve microcirculation, reduce vascular wall permeability, diminish vascular edema, and enhance metabolic processes within the vascular wall. Depending on their influence on various Links of the atherosclerotic process, they can lower cholesterol levels, inhibit its synthesis or absorption, activate Cholesterol Metabolism and elimination from the body, decrease blood triglyceride levels as a source of cholesterol, and reduce blood viscosity (acting as anticoagulants). Antioxidants also protect blood vessel walls by neutralizing the harmful effects of free radicals—products of impaired tissue respiration. Free radicals attack the membranes of cells and cellular Organelles, including Mitochondria, where ATP is generated and accumulated. Membrane blockade leads to even greater impairments in tissue respiration. Antioxidants are of plant origin and serve as sources of Vitamins C, P, and A, as well as the Amino Acids Cysteine, Methionine, and glutamic acid.

Low blood pressure is referred to as hypotension. Hypertensive agents are drugs that cause an increase in blood pressure. Hypertensive agents include substances of diverse origin, chemical structure, and mechanisms of action. In particular, agents that tone the central nervous and cardiovascular systems include so-called adaptogens—predominantly of plant or animal (pantocrine) origin—which maintain vascular tone by supplying physiologically active substances and normalizing blood supply. They also help preserve cell Membrane Structure and normalize calcium, energy, and NUCLEIC ACID METABOLISM. Herbal preparations include liquid extracts of Siberian ginseng (Eleutherococcus), golden root (Rhodiola rosea), Manchurian snakeroot (Aralia mandshurica), high zamaniha, Schisandra chinensis, Sterculia platanifolia, leuzea extract, schisandra, and others.

Agents regulating the function of the digestive system. Effect on appetite. Human diseases are frequently accompanied by decreased appetite and digestive disorders. Appetite is an emotional sensation associated with a person's desire to consume specific food. Unlike the feeling of hunger—an Organism's need for food, which is usually a subjectively unpleasant phenomenon—appetite is based on a desire connected with the expectation of consuming food that should be, and is, a pleasant sensation. Appetite is enhanced by thoughts of the appearance, smell, and taste of food, the environment in which it is consumed, and so on.

The Emergence of appetite is driven by the specific impact of "hungry" blood on the hunger center, the excitation of limbic structures (septum pellucidum, amygdala, hippocampus, cingulate gyrus, etc.), and the cerebral cortex. Ascending activating influences from the hypothalamic initiation centers spread to the cortex. During the first few minutes of eating, appetite increases, especially when the food matches one's preferences. This helps activate the functions of digestive organs: gastric juice secretion increases, the motility of the digestive tract is enhanced ("hunger peristalsis"), and so forth.

Appetite disorders occur in Diseases of the digestive system (peptic ulcer disease of the stomach and duodenum, gastritis, hepatitis, liver cirrhosis, etc.) and frequently develop in neuropsychiatric disorders (Brain Tumors, encephalitis, hysteria, psychosis, etc.), endocrine gland disorders (Diabetes Mellitus, hyperinsulinism, thyrotoxicosis, hypothyroidism), blood system disorders (anemia, leukemia), malignant neoplasms, infectious diseases, and Pregnancy. There are Three types of appetite disorders: a decrease leading to complete loss (anorexia), an increase—sometimes quite drastic (bulimia), and qualitative distortions of appetite involving the desire to consume non-food substances such as chalk, lime, ash, or soil.

Plant-based substances that increase appetite include bitters. The action of plant-derived bitters is associated with the reflex enhancement of digestive juice secretion upon stimulation of taste receptors. This excitation is transmitted to the taste center.

Pure bitters include dandelion root, bog bean leaf, and common centaury herb, while aromatic bitters include calamus rhizome and wormwood herb. Spices, grapes, wine, and beer are also classified among them.

Agents affecting the exocrine function of the liver. Liver diseases impair the formation and excretion of bile.

Choleretic agents are subdivided into those that enhance bile release into the duodenum and those that increase its production. This classification is quite relative.

There are over 100 plants whose preparations can be used as choleretics. The active ingredients in herbal choleretic preparations include essential oils, phytosterols, Flavonoids, and resins. Among essential oils, peppermint, Bulgarian rose, and dill weed oils exhibit choleretic effects. The most valuable agents in this group include preparations derived from everlasting (Helichrysum arenarium), rose hips, corn silk, common barberry, and golden crownbeard. Some herbal choleretic preparations possess spasmolytic, analgesic, and secretin-like activities. Rose hips contain vitamins (ascorbic acid, riboflavin, phylloquinone, tocopherol), carotene, significant amounts of CARBOHYDRATES, citric acid, pectin and tannin substances, as well as macro- and microelements. In terms of ascorbic acid content, rose hips have no equal among plants; the concentration of this vitamin in the fruit can reach 20% or more, increasing as the fruit ripens. Extracts, syrups, tablets, and dragees are prepared from dried rose hips. Rose hip preparations are widely prescribed for hypovitaminosis and avitaminosis. As choleretic and spasmolytic agents, they are active in diseases of the liver, biliary tract, gallbladder, and digestive tract. These preparations help increase the secretory function of The Liver and stomach. A well-known rose hip preparation is cholosas—a thick, dark brown liquid with a characteristic odor and a sweet taste, which exerts choleretic and cholespasmolytic effects.

A well-known preparation, Allochol, is a mixture of dry bile, garlic extract, nettle, and activated charcoal. In addition to affecting liver function, it suppresses putrefactive and fermentative processes in the intestines and enhances gastrointestinal motility.

Cholinokinetic agents (those that enhance bile release) include the alcohols sorbitol and xylitol. Cholespasmolytic agents, which relieve spasms of the biliary tract observed in cholelithiasis and acute cholecystitis, include plant alkaloid preparations such as atropine, platifylline, and papaverine.

Liver diseases and Disorders of Other digestive organs may impair not only exocrine function but also other hepatic functions. Consequently, there is a need for agents that stimulate liver function—hepatoprotectors. In recent years, plant-derived flavonoid and vitamin preparations (tocopherol acetate, ascorbic acid, multivitamins) and glutamic acid have frequently been used as hepatoprotectors. Flavonoids are found in vegetables, fruits, nuts, seeds, Yeast, flowers, and tree bark. They participate in redox reactions, serve as a component of the antioxidant system, and exhibit anti-inflammatory, choleretic, antiviral, antiulcer, and analgesic activities. Plant flavonoids exert a spasmolytic effect on blood vessels, normalize increased Capillary Wall permeability, and inhibit the development of edema. Herbal flavonoid preparations act as natural regulators of gastric mucosal resistance and immunological processes, possessing hepatoprotective and antioxidant activities. The dietary use of natural sources, as well as herbal flavonoid preparations, serves as a prophylaxis for Diseases of the stomach, liver, and cardiovascular system. Herbal flavonoid preparations are mixtures of flavonoids derived from milk thistle fruits, dwarf everlast, fumitory, greater celandine, and dandelion.

Plant-based preparations to enhance intestinal secretory and digestive activity (laxatives): castor oil; anthroglycosides found in the roots of rhubarb, glossy buckthorn, and purging buckthorn.

Plant-based preparations to suppress intestinal secretory and digestive activity (antidiarrheals). Diarrhea is a symptom of numerous pathological conditions and intoxications (dysentery, cholera, sometimes tuberculosis, septic processes, heavy metal poisoning, etc.). Its cause is frequently an inadequate function of the stomach (achylia) and Pancreas, or endocrine gland disorders.

To eliminate diarrhea, astringent, adsorbing, and enveloping agents are used. Additionally, these agents possess non-specific anti-inflammatory action.

Astringents react with tissue proteins to form albuminates in the form of a film that coats The surface of the gastric and intestinal mucosa. This film protects it from mechanical, thermal, and chemical irritations, thereby reducing the flow of pathological impulses from the injury zone, inhibiting the absorption of various substances (including toxic ones). As a result, the inflammatory response in the injury zone disappears, intestinal motility decreases, and the healing of ulcers is accelerated.

Among the group of astringents used to treat diarrhea are plant-based preparations. Tanalbin is the product of the interaction between Tannins and proteins (casein). Unlike tannin, it has no astringent effect on the mucosa of the Oral Cavity, Esophagus, and stomach. Only in the intestines, due to the Digestion of the protein component, is tannin released, which then produces the astringent effect. By protecting receptors from irritation and reducing inflammation, tannin decreases intestinal motility and eliminates diarrhea. Furthermore, due to the constriction of the intestinal mucosal blood vessels, the secretion of intestinal glands is reduced. Infusions and decoctions of St. John's wort herb, blueberries, bird cherry fruits, and tormentil rhizomes are also used as antidiarrheal agents.

Enveloping agents, being high-molecular-weight substances that form colloidal solutions with water, mechanically protect the mucous membrane of the digestive tract from irritation. Consequently, reflex reactions are reduced, intestinal motility is inhibited, and the absorption of substances—including medicinal and toxic ones—in the stomach and intestines is slowed down, creating favorable conditions for resolving the inflammatory process.

Enveloping properties are exhibited by starch, gum arabic, preparations from marsh-mallow root, salep tubers, and flaxseed. Starch (wheat, corn, rice, potato) is used in the form of a colloidal solution obtained by dissolving it in hot water; it is applied topically, internally, and via enemas. Salep tubers and gum arabic are also used to prepare colloidal solutions (mucilages). Marsh-mallow root is used in the form of powder, infusion, dry extract, and syrup as an expectorant, anti-inflammatory, and enveloping agent. Flaxseed is utilized as a decoction and emulsion.

In flatulence, carminative agents derived from peppermint leaves, chamomile flowers, and other plants are also effective. Owing to the essential oils they contain, they reflexively improve the secretory-motor and resorptive functions of the digestive tract and exhibit antimicrobial action.

The primary active ingredient of peppermint essential oil is menthol. When applied to the mucous membrane or rubbed into the skin, it irritates nerve endings, producing a sensation of cold and tingling. The excitation of cold receptors causes superficial blood vessels to constrict and reflexively dilates the Blood vessels of Internal Organs, which presumably explains the reduction of pain sensations in angina pectoris. Menthol also possesses a mild local anesthetic effect. By irritating the receptors of the gastric and intestinal mucosa, menthol enhances the peristalsis and secretion of digestive organs. It also exhibits antiseptic properties, thereby limiting putrefactive and fermentative processes. Peppermint preparations stimulate bile secretion.

Peppermint is used to produce galenicals—infusions and tinctures. They are used as agents that reflexively improve Blood Circulation in the cerebral and cardiac vessels, and as spasmolytics for spastic conditions in the digestive tract, biliary pathways, and pancreatic ducts.

Agents altering renal blood circulation. The increase in diuresis is associated with elevated Glomerular Filtration achieved by dilating renal blood vessels and reducing their vascular resistance. The primary cause is an increase in renal blood flow.

Diuretics are pharmaceutical agents of diverse chemical structure that promote increased urine excretion and a reduction of fluid volume in the body. Because the diuretic action of most drugs is primarily driven by enhanced excretion of salts from the body, this group of agents is also referred to as saluretics.

The primary mechanism of action of diuretics involves their effect on the kidneys, specifically on the Structural and functional unit—the nephron—and the processes occurring within it (glomerular filtration, tubular reabsorption, and secretion).

To understand how diuretics work, let us briefly review The process of Urine Formation.

In the renal glomeruli, hydrostatic pressure drives the filtration of fluid, which contains all blood serum components except for proteins (which cannot pass through the glomerular filter) and lipids. Renal filtration requires the arterial pressure in the glomerular capillaries to exceed the oncotic pressure of blood Serum proteins. A drop in arterial pressure decreases glomerular filtration, whereas an increase enhances it. The rate of glomerular filtration depends not only on renal blood supply, but also on the number of functioning nephrons.

Glomerular filtration in an adult averages 100 mL/min. Over the course of a day, the kidneys filter 150–200 L of fluid, yet only 1.5–2 L of urine is excreted, meaning that 99% of the primary urine is reabsorbed. Reabsorption processes occur throughout the entire length of the nephron: in the proximal tubules, the nephron loop (Loop of Henle), distal tubules, and collecting ducts. The most substantial changes in urine formation can be achieved by targeting tubular reabsorption. In doing so, it must be taken into account that sodium reabsorption in the tubules must be altered first, with water following passively behind it. Sodium ions enter the wall Cells of the tubule from the lumen through the apical membrane. The transport of Na⁺ into the cell is mediated by a specific carrier protein,

Sodium that has entered the tubular cell establishes a sodium pool, which subsequently undergoes active reabsorption. The latter is carried out by specialized pumps located on the basolateral membrane of the tubular wall cells. Several types of such pumps are known; one of them transports Na⁺ in exchange for K⁺. Others mediate the reabsorption of Na⁺ along with Cl^- or HCO₃^-. This constitutes active Na⁺ transport.

About 70–80% of the total filtered Na⁺ is reabsorbed in the proximal tubules, accompanied by the passive reabsorption of water and Cl^-. The proximal segment of the nephron can be a site of diuretic action, though its effect is relatively minor because decreased reabsorption in the proximal tubule triggers a compensatory increase in the nephron loop and distal tubule.

Active Transport of Na⁺ and Cl^- takes place in the nephron loop, and its wall is impermeable to water. Diuretics that act primarily in this section of the nephron are called loop diuretics. Urine formation is completed in the distal segment of the nephron and the collecting ducts. Transport processes here are subject to hormonal regulation, exhibiting the sodium-retaining effect of the mineralocorticoid aldosterone and the water-retaining effect of the antidiuretic hormone vasopressin. Passive secretion of K⁺ from the nephron cells occurs across the apical membrane down an electrochemical gradient. The distal tubule and collecting ducts can also serve as sites of action for diuretics.

Sodium transport in the kidneys is also regulated by other factors (such as estrogens, somatotropic Hormones, Insulin, and Glucagon).

A large group of medicinal plants is used as diuretics. They are best taken for chronic conditions. These include infusions and decoctions of field horsetail, pheasant's eye, bearberry leaves, birch buds, lingonberry leaves, wild strawberry berries, and Kidney tea.

Agents used to stop uterine bleeding. Upon delivery of the fetus and detachment of the Placenta, a portion of the inner uterine mucous membrane separates, accompanied by the rupture of numerous blood vessels. Normally, bleeding is not massive because the tone of the uterine smooth muscle increases, and bundles of muscle fibers constrict the lumina of the blood vessels. When muscle tone is insufficient, a life-threatening condition arises.

Since ancient times, ergot preparations have been used in such cases. Ergot contains 12 alkaloids, among which ergotamine and ergocristine are utilized. In addition, there are herbal preparations—minor hemostatic agents—such as extracts of shepherd's purse, snowball tree (viburnum), nettle, yarrow, barberry, and water pepper. These agents tone the uterine musculature and enhance Blood Coagulation.

6. Agents affecting hematopoiesis. This group includes a variety of substances that either stimulate or suppress the hematopoietic system.

Erythropoiesis (hematopoiesis) stimulants promote Hemoglobin synthesis and red blood cell production, increasing their count per unit volume of blood. Herbal hematopoietic stimulants include wild strawberry fruits, which contain ascorbic and folic acids, Pectins, carbohydrates, and salts of iron, cobalt, calcium, manganese, phosphorus, and others.

Herbal remedies in this group include the fruits of black currant and dog rose, which contain BIOLOGICALLY ACTIVE SUBSTANCES such as Vitamin C, Vitamin P ( rutin), vitamin B₁ (thiamine), provitamin A (carotene), vitamin E (tocopherol), vitamin K (phylloquinone), pectins, flavonoid glycosides, and salts of iron, manganese, and magnesium. For bleeding caused by compromised blood vessel integrity, increased capillary permeability, or insufficient activity of the BLOOD COAGULATION SYSTEM, so-called coagulants—agents that enhance blood clotting—are employed.

Natural antihemorrhagic factors include vitamins K₁ (phylloquinone) and K₂. Vitamin K enhances blood coagulation by increasing the synthesis of prothrombin and other clotting factors (VI, VII, IX, X), primarily in the liver.

Herbal preparations are used as a source of vitamins. They act in concert because they contain other vitamins, bioflavonoids, and various substances that can promote blood clotting. These include preparations of stinging nettle, water pepper, and shepherd's purse.

Anticoagulants are agents that reduce blood clotting. They can be either direct-acting (such as heparin) or indirect-acting. Plant-based indirect anticoagulants act as vitamin K antagonists. They displace vitamin K from the enzyme systems involved in the production of prothrombin and other coagulation factors. Such agents include coumarin derivatives. Coumarin was discovered in 1922–1924 while investigating the causes of decreased clotting and bleeding in cattle in Canada and the USA that had been fed spoiled, decaying clover. Subsequently, dicoumarol—which is formed from coumarin under the action of Fungi—was isolated from spoiled clover. Once its chemical structure was determined, dicoumarol was synthesized artificially.