Alkaloids 1

Question 1

What are Alkaloids?

Answer 1

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.

Question 2

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, _____________________.

Answer 2

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.

Question 3

State the different methods to classify alkaloids:

Answer 3

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).

Question 4

List examples of Alkaloids that are used therapeutically

14

Answer 4

Atropine, quinine, morphine, codeine, hyoscine, vinblastine, colchicine, cocaine, emetine, physostimine, muscarine, camptothecine, caffeine, ephedrine, etc..

Question 5

State the general properties of Alkaloids

STATE SOLUBILITY WHERE POSSIBLE?

Answer 5

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

Question 6

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 _______________.

Answer 6

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.

Question 7

Tropane Alkaloids are biosynthesised from……

Answer 7

Pyrrolidine.

Question 8

A number of the plants containing medicinally important tropane alkaloids belongs to which family?

Answer 8

Solanaceae.

Question 9

List examples of Tropane Alkaloids

deadly nightshade
thornapple
henbane

Answer 9

Atropa belladonna (deadly nightshade)    
   Datura stramonium (thornapple)
       Hyoscyamus niger (henbane)                                                 (included in this family: tomato, potato, pepper

Question 10

Pyrrolidine is converted to intermediates ……

Answer 10

tropine (and methylecgonine).

Question 11

Intermediates tropine (and methylecgonine) are converted into pharmaceutical active compounds such as…

WHAT IS THE PRINCIPAL COMPOUND?

Answer 11

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

Question 12

Facts about Atropa belladonna (deadly nightshade)

Answer 12

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

Question 13

Cultivation of Atropa Belladona….

Answer 13

Plant is cultivated in Europe and US

Question 14

What part of Atropa Belladonna is used to extract alkaloids?

Answer 14

Mainly leaves and stems are used (belladonna herb)

Question 15

______________ are also produced on the plant(A.bellodonna) and contain high levels of alkaloids

Answer 15

Blackberries are also produced on the plant(A.bellodonna) and contain high levels of alkaloids

Question 16

Fresh leaves OF A.BELLADONNA contain __________ and small amounts of ______.

Answer 16

Fresh leaves contain (−)-hyoscyamine and small amounts of hyoscine.

Question 17

Atropine was first isolated in what year?

Answer 17

1819.

Question 18

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 ___________

Answer 18

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

Question 19

Brief History of Datura stramonium (thornapple, Jamestown)

Answer 19

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

Question 20

State the use of Datura stramonium (thornapple, Jamestown) PART 2

Answer 20

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.

Question 21

Why Datura stramonium (thornapple, Jamestown) is cultivated?

Answer 21

Cultivated (Europe and S. America) extensively for its alkaloid content (0.4 %).
Both hyoscyamine : hyoscine present, ratio 2 : 1

Question 22

What is the content of alkaloid in Datura sanguine ?

Answer 22

Datura sanguinea (0.8% alkaloid content) mainly hyoscine

Question 23

Facts about Hyoscyamus niger (henbane)

Answer 23

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

Question 24

State the uses of hyoscyamine and hyoscine

Answer 24

-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).

Question 25

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

Answer 25

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

Question 25

State the clinical application of Atropine sulfate

Answer 25

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

Question 26

State the clinical application of Hyoscine

5

Answer 26

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.

Question 27

List examples of Synthetic/semi-synthetic drugs based on tropane alkaloids

Answer 27

Benzhexol (Trihexylphenidyl), Orphenadrine, and Procyclidine
Granisetron
Cyclopentolate, Homatropine, and Tropicamide
Hyoscine butylbromide
Ipratropium bromide
Tritropium bromide
Umeclidinium

Question 28

What are Benzhexol (Trihexylphenidyl), Orphenadrine, and Procyclidine indicated for?

Answer 28

for treatment of parkinsonism; drug-induced extrapyramidal symptoms.

Question 29

What is Granisetron indicated for?

Answer 29

5-HT3 receptor antagonist (transdermal patch) indicated for the prevention of chemotherapy-induced nausea and vomiting.

Question 30

What are Cyclopentolate, Homatropine, and Tropicamide indicated for?

Answer 30

mydriatic, anterior uveitis.

Question 31

What is Hyoscine butyl bromide indicated for?

Answer 31

Gastrointestinal antispasmodic

Question 32

What are Ipratropium bromide, Tritropium bromide and Umeclidinium bromide indicated for?

Answer 32

Ipratropium bromide (c) and Tritropium bromide (maintenance, long-acting e.g. Spiolto®, Spiriva®) – both for chronic bronchitis. More recently, Umeclidinium bromide for COPD.

Question 33

What is the main source of Methylecgonine alkaloids?

Answer 33

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.

Question 34

Benefits of chewing coca leaves..

Answer 34

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.

Question 35

State the main constituent in coca leaves

Answer 35

The main compound of interest is cocaine. However, it is economical to recover the ecgonine from the other molecules and convert them to cocaine.

Question 36

State the uses of cocaine

Answer 36

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.

Question 37

The form of Cocaine that is highly addictive is called…

Answer 37

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