Alkaloids 1 Flashcards
What are Alkaloids?
Alkaloids are nitrogen-containing organic substances of natural origin with a greater or lesser basic structure.’
Refers to a large number of compounds occurring widely, mainly in the plant kingdom.
State characteristics of Alkaloids
Most are ____________, _______________, ______________ compounds.
They all contain at least one ____________, which in a large majority constitutes part of the ________________.
Display a wide variation in _________________, _____________, botanical sources, _____________________.
Most are crystalline, polycyclic, heterocyclic compounds.
They all contain at least one nitrogen atom, which in a large majority constitutes part of the heterocyclic ring.
Display a wide variation in chemical structure, pharmacological actions, botanical sources, and biogenetic pathways.
State the different methods to classify alkaloids:
According to biosynthetic origins – true alkaloids, proto alkaloids, and pseudo alkaloids.
According to occurrence.
According to (part of) the chemical structure (bearing the nitrogen atom).
List examples of Alkaloids that are used therapeutically
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Atropine, quinine, morphine, codeine, hyoscine, vinblastine, colchicine, cocaine, emetine, physostimine, muscarine, camptothecine, caffeine, ephedrine, etc..
State the general properties of Alkaloids
STATE SOLUBILITY WHERE POSSIBLE?
Alkaloidal salts- soluble in water/insoluble in organic solvents
Alkaloidal base- Soluble in organic solvent/ insoluble in water except;
feebly basic
Quaternary ammonium salt
Amphoteric compounds
How to detect Alkaloids
General tests, which involve _____________ of the compounds, are available (using e.g. _____________ or _________________ reagents)
Specific tests are only available for some of the alkaloids e.g. ________, ___________, and _______________.
General tests, which involve precipitation of the compounds, are available (using e.g. Dragendorff’s or Mayer’s reagents)
Specific tests are only available for some of the alkaloids e.g. atropine, quinine, and morphine.
Tropane Alkaloids are biosynthesised from……
Pyrrolidine.
A number of the plants containing medicinally important tropane alkaloids belongs to which family?
Solanaceae.
List examples of Tropane Alkaloids
deadly nightshade
thornapple
henbane
Atropa belladonna (deadly nightshade) Datura stramonium (thornapple) Hyoscyamus niger (henbane) (included in this family: tomato, potato, pepper
Pyrrolidine is converted to intermediates ……
tropine (and methylecgonine).
Intermediates tropine (and methylecgonine) are converted into pharmaceutical active compounds such as…
WHAT IS THE PRINCIPAL COMPOUND?
hyoscyamine, hyoscine and [cocaine]).
Principal alkaloid in the above plants is -hyoscyamine and small quantities of -hyoscine.
(Hyoscyamine changes to the racemic mixture (atropine) after the plant is extracted. The (+)-enantiomer is relatively less active
Facts about Atropa belladonna (deadly nightshade)
Belladonna’ is from the Italian ‘beautiful woman’. Extracts of the berry were instilled into the eyes to look beautiful. Atropos (Greek) cut thread of life.
Toxicity of this plant has been known for many centuries. Has been associated with witchcraft and related practices especially during the middle ages
Cultivation of Atropa Belladona….
Plant is cultivated in Europe and US
What part of Atropa Belladonna is used to extract alkaloids?
Mainly leaves and stems are used (belladonna herb)
______________ are also produced on the plant(A.bellodonna) and contain high levels of alkaloids
Blackberries are also produced on the plant(A.bellodonna) and contain high levels of alkaloids
Fresh leaves OF A.BELLADONNA contain __________ and small amounts of ______.
Fresh leaves contain (−)-hyoscyamine and small amounts of hyoscine.
Atropine was first isolated in what year?
1819.
State how the extract of belladonna is assayed
This involves a ________. However, also present in the extract are ___________ and related compounds. These compounds will increase the__________. Hence, the procedure requires __________.
The extract is prepared such that the alkaloids are present in their _______ form (not as a ________. The extract is then heated on a steam bath before performing the assay.
Add ________ (in excess)
Titrate with ___________
This involves a back titration. However, also present in the extract are methylpyrroline and related compounds. These compounds will increase the titration value. Hence, the procedure requires removal of these before the titration can be carried out.
The extract is prepared such that the alkaloids are present in their base form (not as a salt). The extract is then heated on a steam bath before performing the assay.
__________________________ Assume the line to be the total alkaloid content in the plant.
__________________________________ add HCl (in excess)
________ Titrate with NaOH
Brief History of Datura stramonium (thornapple, Jamestown)
Historically used by robbers in parts of India to drug travellers. This and a number of related species have been connected with crime over many centuries. The many species have long associations with both magic and medicine in many different parts of the world
State the use of Datura stramonium (thornapple, Jamestown) PART 2
Some species are used as ornamental plants - produces large trumpet shaped flowers. Also produced are capsules (fruit) that contain seeds that are known to contain high levels of alkaloids.
Why Datura stramonium (thornapple, Jamestown) is cultivated?
Cultivated (Europe and S. America) extensively for its alkaloid content (0.4 %).
Both hyoscyamine : hyoscine present, ratio 2 : 1
What is the content of alkaloid in Datura sanguine ?
Datura sanguinea (0.8% alkaloid content) mainly hyoscine
Facts about Hyoscyamus niger (henbane)
Has a long historical association with witchcraft/medicinal herb; used principally to induce hallucinations. There are a number of related species used in different parts of the world.
Leaves and flowering tops of the plant are used. Principal alkaloids are present in a 3:1 ratio
State the uses of hyoscyamine and hyoscine
-hyoscyamine and hyoscine are usually used as their salt form (sulfate and bromide).
These compounds resemble the agonist acetylcholine and act on muscarinic receptors as antagonist (anticholinergic).
State the clinical application of Atropine sulfate
Eye preparations used for ____________ and _________.
Dilation of the pupil to enable internal examination of the eye.
(Gastrointestinal antispasmodic activity)
Beta-blocker overdose; overcome ________ with atropine.
Reduce secretions during _________; Premedication before _____________.
Treat cases of _____________ in combination with other antidotes (2mg every 10 mins until skin is flushed, pupils dilate and bradycardia is reversed).
Control ____________, used to reverse neuromuscular blockade.
Control ___________ after myocardial infarction
Eye preparations used for cycloplegia and anterior uveitis.
Dilation of the pupil to enable internal examination of the eye.
(Gastrointestinal antispasmodic activity)
Beta-blocker overdose; overcome bradycardia with atropine.
Reduce secretions during surgery; Premedication before anaesthesia.
Treat cases of poisoning with organophosphate insecticides in combination with other antidotes (2mg every 10 mins until skin is flushed, pupils dilate and bradycardia is reversed).
Control muscarinic side effects of neostigmine, used to reverse neuromuscular blockade.
Control arrhythmias after myocardial infarction
State the clinical application of Atropine sulfate
Eye preparations used for cycloplegia and anterior uveitis.
Dilation of the pupil to enable internal examination of the eye.
(Gastrointestinal antispasmodic activity)
Beta-blocker overdose; overcome bradycardia with atropine.
Reduce secretions during surgery; Premedication before anaesthesia.
Treat cases of poisoning with organophosphate insecticides in combination with other antidotes (2mg every 10 mins until skin is flushed, pupils dilate and bradycardia is reversed).
Control muscarinic side effects of neostigmine, used to reverse neuromuscular blockade.
Control arrhythmias after myocardial infarction
State the clinical application of Hyoscine
5
Has been used as a ‘truth drug’ in the past. No such activity!
Formulated as a hydrobromide for treatment of motion sickness – hyoscine patches, tablets (see BNF).
Hypersalivation, excess respiratory secretion, colic problems of the bowel, and premedication SC or IM.
List examples of Synthetic/semi-synthetic drugs based on tropane alkaloids
Benzhexol (Trihexylphenidyl), Orphenadrine, and Procyclidine
Granisetron
Cyclopentolate, Homatropine, and Tropicamide
Hyoscine butylbromide
Ipratropium bromide
Tritropium bromide
Umeclidinium
What are Benzhexol (Trihexylphenidyl), Orphenadrine, and Procyclidine indicated for?
for treatment of parkinsonism; drug-induced extrapyramidal symptoms.
What is Granisetron indicated for?
5-HT3 receptor antagonist (transdermal patch) indicated for the prevention of chemotherapy-induced nausea and vomiting.
What are Cyclopentolate, Homatropine, and Tropicamide indicated for?
mydriatic, anterior uveitis.
What is Hyoscine butyl bromide indicated for?
Gastrointestinal antispasmodic
What are Ipratropium bromide, Tritropium bromide and Umeclidinium bromide indicated for?
Ipratropium bromide (c) and Tritropium bromide (maintenance, long-acting e.g. Spiolto®, Spiriva®) – both for chronic bronchitis. More recently, Umeclidinium bromide for COPD.
What is the main source of Methylecgonine alkaloids?
the coca leaves of Erythroxylum spp.
These are cultivated in parts of South America. The properties of the leaves have been known since at least 500 AD. The coca leaves were introduced to Europe by the Spanish conquerors.
Benefits of chewing coca leaves..
Chewing leaves of the plants mixed with lime - common practice amongst the local Indian tribes and still continues in the present day. The brain is stimulated producing a feeling of wellbeing and appetite is reduced. It reduces fatigue and augments physical work.
State the main constituent in coca leaves
The main compound of interest is cocaine. However, it is economical to recover the ecgonine from the other molecules and convert them to cocaine.
State the uses of cocaine
Benzocaine throat lozenges;
Lidocaine, many uses and formulated with other compounds e.g. hydrocortisone, adrenaline, etc.. see BNF;
Bupivacaine, levobupivacaine many uses depending on where anaesthesia is required
Highly limited topical local anesthetic – because of problems of toxicity and addiction, use is restricted to mucosal surfaces
It has been used as a model to prepare a range of synthetic local anesthetics (these produce reversible block of nerve conduction and prevent nerve depolarization and thus transmission across the nerves) that have fewer side effects.
The form of Cocaine that is highly addictive is called…
CRACK
The form known as ‘crack’ is the free base of the alkaloid is highly addictive since it is absorbed rapidly from the mucous membranes to the brain