19 - MIXED ORIGIN ALKALOIDS Flashcards
MIEXED ORIGIN ALKALOIDS
A.- Imidazole alkaloids: histidine derivatives • B.- Terpenoid alkaloids: Diterpenoid Steroidal • C.- Purine alkaloids
HISTIDINE-DERIVED ALKALOIDS (CHARACTERISTICS AND CRUDE DRUGS)
The amino acid L-histidine contains an imidazole ring, and a precursor of alkaloids containing this ring system.
Jeborandi, Pilocarpus
Alkaloid; policarpine
HISTIDINE-DERIVED ALKALOIDS (ALKALOIDS)
The crude drug contains 0.5–1.0% of the imidazole alkaloid pilocarpine together with small amounts of pilosine and related structures such as isopilocarpine.
PILOCARPINE
HISTIDINE-DERIVED ALKALOIDS
Pilocarpine salts are valuable in ophthalmic practice and are used in
eyedrops as miotic (cause contraction of the pupil of the eye, being
antagonistic to that of atropine) and for the treatment of glaucoma (serve
to increase the irrigation of the eye and relieve pressure).
Pilocarpine is a cholinergic agent and stimulates the muscarinic
receptors in the eye, causing constriction of the pupil and enhancement
of outflow of aqueous humour.
As antagonistic to atropine, pilocarpine relief dryness of the mouth that
results in patients treated with radiotherapy for mouth and throat
cancers.
HISTIDINE-DERIVED ALKALOIDS (SPANISH PHARMACEUTIC SPECIALITIES)
Salagen® tablets, composition per unit:
Pilocarpine hydrochloride 5 mg
Therapeutic indications: Relief of symptoms of salivary glands hypofunction
in patients with severe xerostomia (dry mouth), post-radiotherapy in head and
neck cancer. Treatment of symptoms of dry mouth and dry eyes in patients with
Sjögren’s syndrome.
Colircusí Pilocarpina® eye drops, composition: 2% solution of pilocarpine
chloride.
Therapeutic indications: glaucoma, induction of myosis.
Salagen® tablets
HISTIDINE-DERIVED ALKALOIDS (SPANISH PHARMACEUTIC SPECIALITIES)
Salagen® tablets, composition per unit:
Pilocarpine hydrochloride 5 mg
Therapeutic indications: Relief of symptoms of salivary glands hypofunction
in patients with severe xerostomia (dry mouth), post-radiotherapy in head and
neck cancer. Treatment of symptoms of dry mouth and dry eyes in patients with
Sjögren’s syndrome.
Colircusí Pilocarpina® eye drops,
HISTIDINE-DERIVED ALKALOIDS (SPANISH PHARMACEUTIC SPECIALITIES)
Colircusí Pilocarpina® eye drops, composition: 2% solution of pilocarpine
chloride.
Therapeutic indications: glaucoma, induction of myosis.
TERPENOID ALKALOIDS
Many alkaloids are synthesized primarily from non-amino acid precursors,
being the nitrogen atom inserted into the structure at a relatively late stage.
These structures are frequently based on terpenoid or steroidal skeletons,
and in most of cases the nitrogen atom is donated from an amino acid source
through a transamination reaction with a suitable aldehyde or ketone.
DITERPENOID ALKALOIDS
Aconite, Wolfsbane, Monkshood Root of Aconitum napellus L. (Ranunculaceae) The crude drug contains toxic alkaloids (0.3–1.5%) that are complex diterpene-derived esters. Aconitine (main compound, about 30%) with no therapeutic use due to its toxicity, is a diester of aconine with acetic and benzoic acids. These alkaloids appear to behave as neurotoxins by acting on sodium channels.
STEROIDEAL ALKALOIDS (CHARACTERISTICS AND CRUE DRUGS)
Steroidal alkaloids arise by the inclusion of a basic nitrogen atom at some
point in the steroid molecule.
Kurchi, Holarrhena
White Hellebore
Kurchi, Holarrhena
STEROIDEAL ALKALOIDS
Kurchi contains numerous steroidal-type alkaloids (1.8-4.5%)
including conessine used as starting material of some hormones
such as aldosterone.
Antiprotozoal activity. The drug is used as a treatment for amoebic
dysentery.
White Hellebore
STEROIDEAL ALKALOIDS
Alkaloids: jervine, protoveratrine A, protoveratrine B (protoveratrines
are medicinal alkaloids esters of protoverine)
Antihypertensive activity. Narrow therapeutic range.
Solanaceae containing steroidal alkaloids
Many plants in the Solanaceae family accumulate steroidal alkaloids based
on a C27 cholestane skeleton. They are usually present as glycosides which
have as the saponins, surface activity and hemolytic properties.
Nevertheless these compounds are also toxic by ingestion.
Since the production of medicinal steroids from steroidal saponins
requires preliminary degradation to remove the ring systems containing
the original cholesterol side-chain, it is indifferent whether these rings
contain oxygen or nitrogen.
In this sense, plants rich in solasodine or solanidine could also be
employed for commercial steroid production.
Potato and Woody Nighshade
Potato
Solanaceae containing steroidal alkaloids
Solanidine
Woody Nighshade
Solanaceae containing steroidal alkaloids
Toxicity due to soladulcidine and solasodine glycosides
PURINE ALKALOIDS
The purine-derivatives caffeine, theobromine, and theophylline are
usually referred to as purine alkaloids. As alkaloids they have a
limited distribution, but their origin is very closely linked with those of
the purine bases adenine and guanine, fundamental components of
nucleosides, nucleotides, and the nucleic acids.
So purine bases are bicyclic structures with four heterocyclic nitrogen
atoms and chemically derived from the purine ring (condensation of a
pyrimidine with an imidazole nucleus).
PURINE ALKALOIDS NAMES
Caffeine
Theophylline
Theobromine
PURINE ALKALOIDS, SPECIAL CHARACTERISTICS
They ae not derived from amino acids, and water soluble alkaloids
PURINE ALKALOIDS, SPECIFIC DETECTION
Murexide reaction (after extraction with CH2Cl2,
filtration and solvent evaporation, the dry residue is treated with hydrogen
peroxide in the presence of dilute hydrochloric acid. After evaporation to
dryness, a bright red color develops, which turns purple upon addition of
dilute aqueous ammonia).
PURINE ALKALOIDS SOME CHARACTERISTICS
The major sources of these compounds are in beverages such as tea,
coffee, cocoa, and cola, which owe their stimulant properties to these
water-soluble alkaloids. They competitively inhibit phosphodiesterase,
resulting in an increase in cyclic AMP and subsequent release of
adrenaline.
This leads to a stimulation of the CNS, a relaxation of bronchial smooth
muscle, and induction of diuresis, as main effects. These effects vary in
the three compounds. Caffeine is the best CNS stimulant, and has weak
diuretic action. Theobromine has little stimulant action, but has more
diuretic activity and also muscle relaxant properties.
Theophylline also has low stimulant action and is an effective diuretic, but
it relaxes smooth muscle better than caffeine or theobromine.
PURINE ALKALOIDS, ACTION AND EFFECTS ON THE CNS
Central Nervous System
Activation widespread, especially in case of depression.
a) Cortex
Cortical stimulant, stimulate the psychic functions and decrease the
sensation of fatigue.
Increase the capacity to maintain intellectual effort.
Very high doses can induce nervousness, insomnia and tremors.
In epilepsy, can trigger an attack
b) Bulb
Stimulate bulbar centers: the respiratory center, the vomiting center.
High doses: nausea and vomiting.
In chronic treatment: warning of toxicity.
PURINE ALKALOIDS, ACTION AND EFFECTS, RESPIRATORY SYSTEM
Respiratory system
Stimulation, due to an increase in sensitivity of carbon dioxide centers in
the brain stem, especially if the respiration is depressed.
Bronchial relaxation: anti-asthma. Theophylline is a non-specific bronchial smooth muscle relaxant.
PURINE ALKALOIDS, ACTION AND EFFECTS, GI SYSTEM, CV SYSTEM, SKELETAL MUSCLE, KIDNEY AND METABOLISM
Gastrointestinal system
Relaxation of the bile, intestinal etc., smooth muscle.
Stimulation of gastric secretion.
Cardiovascular system
a) Heart
Not very powerful cardiac stimulant. Caffeine has a positive inotropic effect
and causes in high doses tachycardia and arrhythmia.
b) Coronary vasodilation
c) Vessels: vasoconstriction
Skeletal muscle
Increase contractile response. They mask the feeling of fatigue. Increases
the capacity for muscular work.
Kidney: diuretic activity, linked to an increase in glomerular filtration. The
effect of theophylline is stronger than that of caffeine.
Metabolism: increase the basal metabolism. 0.5 g of caffeine may increase
metabolism 10-25%.
PURINE ALKALOIDS, INDICATINS
Caffeine is used medicinally as a CNS stimulant, usually combined with
another therapeutic agent in analgesic preparations.
Theobromine is of value as a diuretic and smooth muscle relaxant, but is
not now routinely used.
Theophylline is an important smooth muscle relaxant for relief of
bronchospasm, and is frequently dispensed in slow release formulations to
reduce side-effects.
Respiratory system: formulation of theophylline in acute attack of chronic
asthma, COPD (chronic obstructive pulmonary disease), and apnea of
prematurity
CNS intoxication by depressant: alcohol, barbiturates, etc.
Kidney: diuretics.
In combination with other drugs for various purposes.
ASSOCIATIONS OF CAFFEINE
Caffeine is associated with analgesics: flu remedy + analgesics;
migraine: ergotamine, dihydroergotamine;
sea sickness: H2
-antihistamine (Biodramina caffeine®
, Cinfamar caffeine®),
coronary vasodilators: nitroglycerin (Cafinitrina®).
PHARMACEUTIC SPECIALITIES WITH THEOPHYLLINE
Eufilina®
Anhydrous theophylline, 200 mg Therapeutic indications: treatment of
acute bronchial asthma and bronchospasm associated with chronic
bronchitis or pulmonary emphysema.
EPIGALLOCATEHIN-3-O-GALLATE
An infusion of tea contains in additin to caffeine a mixture of polyphenols icluding this. It possesses strong beneficial effects aganst cardiovascular disease, cancers and the ageing process.
The tea cotains 1-5% caffeine and 10-24% of condensed atannins, and small quantities of theobromine, theophylline and voltile oil. Polysaccahariedes,proteins, vitamins C and B, phenolic acids, flavonoids, proanthocyanidins, eigallocatechin gallate,etc.
Cocoa or Cacao
It has nutritive, stimulant and diuretic properties. Ccabo butter can be used as fatty excpient, it is emploed in pharmacy as suppository base. It contains glycerides of oleic (35%), palmitic (26%), and linoleic (3%) acids. Cocoa seed contain 35-50% of oil, 1-4 theobromine andd 02-05% caffeine, and also water-soluble polyphenols and volatile oils.
Kola, Cola
Kola seedds contain caffeine and small amount of theobromine. Also contain about 5-10% of tannins partly bound to purine alkaloids. Fresh cola seed are chewd in troical countires as stimulant, and vast quantities of dried seeds are processed in the manufacturate of carbonated, no- alcoholic beverages. Several formulations are used in functiona asthenia.
Mate, Praguay Tea
The dried leaf contains 0.8-1,7% caffeine and smaller amouns of theobromine (0.3-9.9%) . Considerable amouns (10-16%) of chlorogenic acid and litter amount of volatile oil are also present.
Guarana, Brazillian Cocoa
The curde drug, has no marked odour but an astringer bitter taste is noted.
Guaeana, Brazillian Cocoa paste
It is prepared from the seed. Paste obtained by the indigenous people of the Amazon with roasted and crushed Paullinia cupana seeds. t is used for the preparation of stimulants and energetic drinks. In the west it is a popuar remedy for comating fatigue, for slimming and for the treatment of diarrhea.
Guaranine
Guarana contains guaranine (matine, tein, caffeine), in a large proportion (3.5-5&), and ther methyl xanthines such as thebromine and theophylline. It also has a high tannin content (12%), flavonoids, resin, saponins, essential oil and mucilages.
Guarana, medicinal properties
Guarana seed etractsave antioidant and antimicrobial roperties that make them powerfu preservatives. Guarana is widely available as tablets and casules, or as extracts , in health food shops where it is promoted to relieve mental and physical fatigue.
