MP and MPM containing MP and MPM containing cardiac glycosidescardiac glycosides

Cardiac glycosidesCardiac glycosides are a big group of are a big group of substances, derivatives of substances, derivatives of

cyclopenthaneperhydropenantrene, cyclopenthaneperhydropenantrene, which selectively affect the heart which selectively affect the heart

muscle.muscle. The introduction of the foxglove into British The introduction of the foxglove into British

medicine for treatment of dropsy by the medicine for treatment of dropsy by the Birmingham physician and botanist William Birmingham physician and botanist William Whithering, in 1785, constitutes one of medicine. Whithering, in 1785, constitutes one of medicine. It was not realised at that time, however, that It was not realised at that time, however, that dropsy could be the result of a heart condition. dropsy could be the result of a heart condition. Before the introduction of digitalis it was treated Before the introduction of digitalis it was treated by the oral administration of dried and powdered by the oral administration of dried and powdered toad-skinstoad-skins; later investigations were to show that ; later investigations were to show that this treatment too, did not lack a pharmacological this treatment too, did not lack a pharmacological basis.basis.

The clinical effect in cases of congestive heart The clinical effect in cases of congestive heart failure is to increase the force of myocardial failure is to increase the force of myocardial contraction (the positive inotropic effect) contraction (the positive inotropic effect) resulting in a complete emptying of the resulting in a complete emptying of the ventricles. As a result of depression of ventricles. As a result of depression of conduction in the bundle of His, the conduction in the bundle of His, the atrioventicular conduction time is increased, atrioventicular conduction time is increased, resulting in an extended P-R interval on the resulting in an extended P-R interval on the electrocardiogram. Arising from their vagus electrocardiogram. Arising from their vagus effects, the digitalis glycosides are also used effects, the digitalis glycosides are also used to control supraventicular (atrial) cardiac to control supraventicular (atrial) cardiac arrhythmias. The diuretic action of digitalis, arrhythmias. The diuretic action of digitalis, important in the treatment of dropsy, arises important in the treatment of dropsy, arises from the improved circulatory effect.from the improved circulatory effect.

cyclopentane perhydro phenanthrene

Cardenolide Bufadienolide

D-digitoxose D-Cymarose L-Oleandrose

Cardenolides with methyl radical inCardenolides with methyl radical in С-10С-10 position belong to Digitalis position belong to Digitalis groupgroup, , and cardenolids with and cardenolids with aldehides radical in aldehides radical in С-10 – С-10 – Strophanthus group.Strophanthus group.

Сировину зберігають за списком Б; Сировину зберігають за списком Б; насіння строфанта, серцеві насіння строфанта, серцеві глікозиди та більшість їх глікозиди та більшість їх препаратів – списком А. препаратів – списком А.

CollectionCollectionEither first- or second-year digitalis leavesare Either first- or second-year digitalis leavesare

permitted by pharmacopoeias. permitted by pharmacopoeias. There has been a long-standing general belief that There has been a long-standing general belief that

the pharmacological activity of leaves increases the pharmacological activity of leaves increases during the course of a day to reach a maximum in during the course of a day to reach a maximum in the early afternoon. the early afternoon.

After collection the leaves should be dried as rapidly After collection the leaves should be dried as rapidly as possible at a temperature of about 60 degree as possible at a temperature of about 60 degree and subsequently stored in airtight containers and subsequently stored in airtight containers protected from the light. Their moisture content protected from the light. Their moisture content should not be more than about 60 %should not be more than about 60 %

Distribution in natureDistribution in nature

In plants cardiac glycosides appear to be In plants cardiac glycosides appear to be confined to the Angiosperms. confined to the Angiosperms. Cardenolides are the most common and Cardenolides are the most common and are particularly abundant in the are particularly abundant in the Apocyanaceae and Asclepidiaceae, but Apocyanaceae and Asclepidiaceae, but are also found in some Liliaceae, are also found in some Liliaceae, Ranunculaceae, Moraceae, Cruciferae, Ranunculaceae, Moraceae, Cruciferae, Euphorbiaceae, Tiliaceae, Leguminosae Euphorbiaceae, Tiliaceae, Leguminosae and Scrophulariaceae.and Scrophulariaceae.

Physicochemical properties Physicochemical properties

Cardiac glycosides are colourless or white Cardiac glycosides are colourless or white crystals, or amorphous substances, without crystals, or amorphous substances, without odour, taste is bitter, they have melting odour, taste is bitter, they have melting temperature (100-270ºC), optically active, temperature (100-270ºC), optically active, many of them have fluorescence in UV-light. many of them have fluorescence in UV-light. Many of them are bad soluble in water, good Many of them are bad soluble in water, good soluble in water solutions of methyl and ethyl soluble in water solutions of methyl and ethyl alcohols. Glycosides with long carbon chain alcohols. Glycosides with long carbon chain are better soluble in water and water-alcohol are better soluble in water and water-alcohol solutions, aglycones- in organic solvents. solutions, aglycones- in organic solvents. They can hydrolyse. They can hydrolyse.

Methods of obtaining Methods of obtaining and testsand tests

The main method of obtaining of The main method of obtaining of cardiac glycosides is extraction.cardiac glycosides is extraction.

For the identification of CG 3 types For the identification of CG 3 types of reaction are usually used: for of reaction are usually used: for steroid ring, for lactone ring and steroid ring, for lactone ring and for hydrocarbon ring.for hydrocarbon ring.

Biological actionBiological action

The pharmacological effectiveness of The pharmacological effectiveness of the cardioactive glycosides is the cardioactive glycosides is dependent on both the aglycones dependent on both the aglycones and the sugar attachments; the and the sugar attachments; the inherent activity resides in the inherent activity resides in the aglycone, but the sugars render the aglycone, but the sugars render the compounds more soluble and compounds more soluble and increase the power of fixation of the increase the power of fixation of the glycosides to the heart muscle. glycosides to the heart muscle.

The overall action of the digitalis The overall action of the digitalis glycosides is complicated by the number glycosides is complicated by the number of different effects produced, and their of different effects produced, and their exact mode of action on myocardial exact mode of action on myocardial muscle in relation to current views on muscle in relation to current views on cardiac muscle physiology is still an area cardiac muscle physiology is still an area of investigation. Digitalis is probably acts of investigation. Digitalis is probably acts in competition with K+ions for specific in competition with K+ions for specific receptor enzyme (ATPase) sites in the receptor enzyme (ATPase) sites in the cell membranes of cardiac muscle and is cell membranes of cardiac muscle and is particularly successful during the particularly successful during the depolarization phase of the muscle when depolarization phase of the muscle when there is an influs of Na+ ions. there is an influs of Na+ ions.

MP and MPM containing MP and MPM containing cardiac glycosidescardiac glycosides

Folia DigitalisFolia DigitalisDigitalis purpurea- Purple Digitalis purpurea- Purple FoxgloveFoxgloveScrophulariaceaeScrophulariaceae Constituents. Constituents. Purple Foxglove contains Purple Foxglove contains the glycosides glucogitaloxine, the glycosides glucogitaloxine, purpureaglycoside A and B; the saponins purpureaglycoside A and B; the saponins digitonin, digitsaponin and gitin, volatile digitonin, digitsaponin and gitin, volatile oil containing digitalosmin; tannin, an oil containing digitalosmin; tannin, an irritant resin termed digitalic acid, a irritant resin termed digitalic acid, a yellow colouring substance termed yellow colouring substance termed digitoflavone or luteolin, an oxydase, etc. digitoflavone or luteolin, an oxydase, etc.

Digitalis is extensively used as a cardiac Digitalis is extensively used as a cardiac stimulant and tonic and as a diuretic. stimulant and tonic and as a diuretic. Digitoxin, gitoxin and cordigitDigitoxin, gitoxin and cordigit are used in are used in treatment of chronic (or less often acute) treatment of chronic (or less often acute) heart failure of II and III levels. The heart failure of II and III levels. The action of these medicines begins in 30-60 action of these medicines begins in 30-60 min, and lasts from 8 to 24 hours. The min, and lasts from 8 to 24 hours. The medicines from Digitalis can accumulate medicines from Digitalis can accumulate in the body and thus they must be in the body and thus they must be combined with other medicines, which do combined with other medicines, which do not accumulate.not accumulate.

Folia Digitalis lanataeFolia Digitalis lanataeDigitalis lanata- Grecian Digitalis lanata- Grecian FoxgloveFoxgloveScrophulariaceaeScrophulariaceae

Constituents. Constituents. The leaves contain the The leaves contain the crystalline glycosides digitoxin, crystalline glycosides digitoxin, gitoxin and digoxin each occurring gitoxin and digoxin each occurring free as well as combined with an free as well as combined with an acetyl group and a molecule of acetyl group and a molecule of dextrose. In the combined form, dextrose. In the combined form, these substances are known these substances are known respectively as lanatosides A, B and respectively as lanatosides A, B and C. C.

Uses. Uses. Medicines from Digitalis lanata Medicines from Digitalis lanata have more benefits than medicines have more benefits than medicines from Digitalis purpurea: they less from Digitalis purpurea: they less accumulate in body, have faster accumulate in body, have faster action on heart, more compatible.action on heart, more compatible.

In medicine In medicine digixin, celanid, isolanid, digixin, celanid, isolanid, lanicor, lanatosidlanicor, lanatosid and and lanatosid Clanatosid C are are widely used.widely used.

Semina StrophantiSemina StrophantiStrophantus Kombe- Strophantus Kombe- Strophantus Strophantus ApocynaceaeApocynaceae Constituents. Constituents. Up to 3% of a bitter Up to 3% of a bitter

glycoside known as a strophantin glycoside known as a strophantin and A-strophantin, about 30% of and A-strophantin, about 30% of fixed oil, kombic acid, strophantic fixed oil, kombic acid, strophantic acid, the alkaloids trigonelline and acid, the alkaloids trigonelline and choline, etc. choline, etc.

Uses. Uses. Cardiac stimulant (of Cardiac stimulant (of strophant group) and diuretic. For strophant group) and diuretic. For treatment treatment Strophantin-KStrophantin-K (in (in ampoules) is widely used. ampoules) is widely used. Strophantin-GStrophantin-G is used as a is used as a standard in biological assessment standard in biological assessment of medicines.of medicines.

Herba Adonidis vernalisHerba Adonidis vernalisAdonis vernalis- Pheasant’s Adonis vernalis- Pheasant’s Eye, False Hellebore, Eye, False Hellebore, Spring AdonisSpring AdonisRanunculaceaeRanunculaceae

Constituents. Constituents. The amorphous The amorphous cardiac glycosides, adonidoside and cardiac glycosides, adonidoside and adonivernoside; adonidic acid; adonivernoside; adonidic acid; adonitol, choline, resin, etc. Adonidin adonitol, choline, resin, etc. Adonidin is a mixture of the glycosides with is a mixture of the glycosides with adonidic acid. adonidic acid.

Uses. Uses. Together with cardiotonic Together with cardiotonic action, which is lower than action, which is lower than strophantus and foxglove have, strophantus and foxglove have, medicines from Adonis have sedative medicines from Adonis have sedative action on CNS. Infusion is part of action on CNS. Infusion is part of Behterev’s mixtureBehterev’s mixture, which also , which also contains sodium bromide and codein. contains sodium bromide and codein. Dry extract of adonisDry extract of adonis (1:1 or 2:1) is (1:1 or 2:1) is used for the production of tablets used for the production of tablets and infusions. Tablets and infusions. Tablets adonis-bromadonis-brom are used as sedative agent. Adonisid are used as sedative agent. Adonisid is part of is part of cardiovalen, cardiofit, dry cardiovalen, cardiofit, dry adonisidadonisid..

Herba ConvallariaeHerba ConvallariaeFolia ConvallariaeFolia ConvallariaeFlores ConvallariaeFlores ConvallariaeConvallaria majalis- Lily-of-Convallaria majalis- Lily-of-the-Valleythe-ValleyConvallariaceaeConvallariaceae

Constituents. Constituents. The cardiac The cardiac tonic glycoside convallatoxin tonic glycoside convallatoxin occurring in needle-like occurring in needle-like crystals only slightly soluble crystals only slightly soluble in water; the glycoside in water; the glycoside convallamarin, soluble in convallamarin, soluble in water, to which is ascribed water, to which is ascribed cardiac stimulant properties; cardiac stimulant properties; another glycoside convallarin another glycoside convallarin (insoluble in water) which is (insoluble in water) which is emetic and cathartic; starch; emetic and cathartic; starch; calcium oxalate, etc. calcium oxalate, etc.

Uses. Uses. TinctureTincture (1:10), (1:10), corglicon, Zelenin drops, corglicon, Zelenin drops, convaflavinconvaflavin is used as is used as cholagogue medicine and cholagogue medicine and part of part of marelinmarelin..

Herba Erysimi canescentis Herba Erysimi canescentis recensrecensErysimum canescens- Erysimum canescens- ErysimumErysimumBrassicaceaeBrassicaceae

Constituents.Constituents. The cardiac The cardiac tonic glycoside (up to 6% in tonic glycoside (up to 6% in seeds and 1 to 1.5% in seeds and 1 to 1.5% in leaves). The main glycosides leaves). The main glycosides are erysimin and are erysimin and erysimoside.erysimoside.

Uses. Uses. Employed as cardiac Employed as cardiac stimulant. Pharmacological stimulant. Pharmacological action is similar to action is similar to Strophantus preparations. Strophantus preparations. Erysimin has cardiotonic, Erysimin has cardiotonic, sedative and diuretic action. sedative and diuretic action. Juice is part of Juice is part of cardiovalencardiovalen..