a) Atropine

• Atropine is commonly used in ophthalmological eyedrops to enlarge pupils, paralyze the accommodation reflex, and enable the ophthalmic examination.

• It is a tropane Alkaloid extracted from Deadly Nightshade (Atropa Belladonna), jimsonweed (Daturastramonium), Mandrake (Mandragoraofficinarum) and other plants of the family Solanaceae/Nightshades.

• It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects.

• Solanaceae/Nightshades plants biologically active Alkaloids (including tropane Alkaloids) is a competitive antagonist for the muscarinic acetylcholine receptor.

• It is classified as an anti- Cholinergic drug.

• The racemic mixture of (-)-Hyoscyamine and (+)-Hyoscyamine is called atropine (EFSA Journal, 2013).

Uses of Atropine

• Ophthalmic use – Topical atropine is used as a cycloplegic, to temporarily paralyzethe accommodation reflex, and as a mydriatic, to dilate the pupils. Atropine degrades slowly (typically wearing off in 7-14 days) so it is generally used as a therapeutic mydriatic, where it induces mydriasis by blocking contraction of the circular-pupillary sphincter muscle, which is normally stimulated byacetylcholine release, thereby allowing the radial pupillary dilatormuscle to contract and dilate the pupil.

• Resuscitation – Injections of atropine are used in the treatment of bradycardia (anextremely low heart rate), asystole and pulse-less electrical activity (PEA) in cardiac arrest, because the main action of thevagus nerve of the parasympathetic system on The Heart is to decrease heart rate (also useful in treating second degree heart block).

• Secretions and broncho constriction – Atropine action on the parasympathetic Nervous System inhibits salivary, Sweat, and mucus glands, which can be useful in treating hyperhidrosis, and can prevent the death rattle of dying patients.

• Treatment for organo-phosphate poisoning – Atropine is not an actual antidote for organo-phosphate Poisoning, however by blocking the action of acetylcholine at muscarinic receptors (also serves as a treatment for Poisoning by organo-phosphate insecticides and nerve gases), given as a treatment for SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis, Gastro-intestinal motility, Emesis) symptoms caused by organo-phosphate Poisoning.

• Optical penalization – In refractive and accommodative amblyopia, when occlusion is not appropriate sometimes atropine is given to induce blur in the good Eye.

Adverse Effects and Overdose of Atropine

• Adverse reactions to atropine (include ventricular fibrillation, supra ventricular or ventricular tachycardia, Dizziness, Nausea, blurred vision, loss of balance, dilated pupils, photophobia, and, possibly, notably in the Elderly, extreme confusion, extreme dissociative hallucinations, and excitation).

• In overdoses, atropine is Poisonous.

• Atropine is sometimes added to other potentially addictive drugs, particularly Anti-diarrhea opioid drugs.

• Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical heart rate slowing when given at very low doses).

Oral Administration of Atropine (in single doses)

• 0.5–1 mg up to three (3) times daily is used to treat smooth muscle spasms in the gastro-intestinal tract, which causes side effects (including slight cardiac slowing and dryness of mouth).

• 2–5 mg is associated with rapid heart rate, dilated pupils, blurring of vision, difficulties of speaking and swallowing, and dry and hot Skin.

• 10 mg or more atropine lead to rapid and weak pulse, ataxia, restlessness, excitement, hallucinations, delirium, and coma.

b) Hyoscyamine ([-]-Hyoscyamine, [+]-Hyoscyamine)

• Hyoscyamine is used in the treatment of visceral spasm in oral single doses of 0.15–0.3 mg up to four (4) times daily, showing the same adverse effects as atropine.

c) Scopolamine (scopolamine[[-]-hyoscine)

• Scopolamine is administered orally in single doses of 0.15–0.3 mg up to four times daily in the prevention of postoperative Dizziness and Motion Sickness.

d) Cocaine

• Cocaine is the second most popular psycho-Stimulant (after cannabis), temporarily improving mental and physical functions.

• Cocaine inhibits serotonin, norepinephrine, and dopamine reuptake.

• In higher doses, cocaine may evoke the blockage of Sodium channels resulting in cardiac death.

• Chronic intake may cause serious transmitter level disorders leading to Depressions, suicide attempts, Insomnia, or psychomotor retardation.

• It (benzoyl methyl ecgonine) is a crystalline tropane Alkaloid that is obtained from the leaves of the coca plant(Erythroxylon coca).

• The name comes from “coca” in addition to the Alkaloid suffix-ine, forming cocaine.

• It is a Stimulant of the central Nervous System and an appetite suppressant.

• Its possession, cultivation, and distribution are illegal for non-medicinal and non-government sanctioned purposes in virtually all parts of the world.

• The cocaine Alkaloid was First isolated by the German chemist Friedrich Gaedcke in 1855.

• Cocaine use can lead to severe mental, physical and social problems, where its addiction/dependence is physical and psychological on the regular use, resulting in physiological damage, lethargy, psychosis, Depression, or apotentially fatal overdose.

Two (2) Primary Forms of Cocaine

1) Cocaine Hydrochloride is an odourless white powder, usually snorted (intra-nasal use) or injected (intra-venous use). Crack cocaine is a flaky, hard Material obtained by adding ammonia or Sodium bicarbonate (baking soda) and Water to cocaine hydroChloride and heating the resulting precipitated powder.

2) Cocaine Alkaloid is made into freebase or crack (not Water soluble) and smoked, resulting in a faster, more intense high than injecting or snorting.

Acute Effects & Health Issues of Cocaine

• Cocaine is a potent central Nervous System Stimulant, where its effects can last from 20 minutes to several hours, depending upon the Dosage of cocaine taken, purity, and method of administration.

• The initial signs of stimulation are hyper-activity, restlessness, increased blood pressure, increased heart rate and euphoria.

• The euphoria is sometimes followed by feelings of discomfort, Depression and a craving to experience the drug again.

• Side effects can include twitching, paranoia, and Sexual Impotence, which usually increase with frequent usage.

• With excessive or prolonged use, the drug can cause itching, tachycardia, hallucinations, and paranoid delusions.

• Overdoses cause tachyArrhythmias and a marked elevation of blood pressure.

• Cocaine may lead to death from Respiratory failure, Stroke, cerebral hemorrhage, or heart-failure.

• The “crash” is accompanied with jitters (muscle spasms throughout the body), muscle weakness, Headaches, Dizziness, and suicidal thoughts.

Chronic Effects & Health issues of Cocaine

• Chronic cocaine intake causes brain cells to adapt functionally to strong imbalances of transmitter levels in order to compensate extremes, therefore the receptors disappear from the cell surface (or re-appear on it), resulting more or less in an “off” or “working mode” respectively, or they change their down/upregulation (susceptibility for binding partners/ligands mechanisms).

• Physical side effects from chronic Smoking of cocaine include hemoptysis, bronchospasm, pruritus, Fever, diffuse alveolar infiltrates without effusions, pulmonary and systemic eosinophilia, chest pain, lung Trauma, sore throat, Asthma, hoarse voice, Dyspnea (shortness of breath), and an aching, Colds (Flu)-like syndrome.

• Tooth enamel and lead to Gingivitis (Periodontitis): Chronic intra-nasal usage can degrade the cartilage separating the nostrils (the septum nasi), leading eventually to its complete disappearance.

e) Tigloidine

Tropane Alkaloids Details

• Tropane Alkaloids are synthesized ultimately from the Amino Acids ornithine, putrescine (decarboxylated ornithine), or Proline.
• They contain a pyrrolidine and piperidine ring meshed together, and are largely confined to the Solanaceae family, though some are found sprinkled through other families.
• The most well known tropane Alkaloids are atropine, Hyoscyamine and scopolamine, found exclusively in Solanaceae family plants.
• These Alkaloids are all anti-cholinergic and are used to decrease smooth muscle spasms and reduce secretions, particularly in the Digestive tract.
• Scopolamine is also used to prevent Motion Sickness and as presurgical medication because of its unique central Nervous System depressing effects, not seen with Hyoscyamine.
• Higher doses of Hyoscyamine are hallucinogenic, and these plants have historically been used for ritual purposes. Ipratropium (an important bronchodilator drug) is a synthetic derivative of Hyoscyamine.

• Tropane Alkaloids are a class of Bicyclic Alkaloids and secondary metabolites that contain a tropane ring in their chemical structure.
• Most Tropane Alkaloids are toxic to humans with characterized effects such as dryness of the mucosa of the upper Digestive and Respiratory tract, Constipation, pupil dilatation, disturbance of vision, photophobia, dose-dependent occurrence of hyper-tension (or hypo-tension), bradycardia, tachycardia, Arrhythmias, Nervousness, restlessness, irritability, disorientation, ataxia, seizures, and Respiratory Depression.
• Typical adverse effects for anti-Cholinergic drugs such as dryness of the mouth, changes in heart rate, and disturbance of vision are reported within the range of the therapeutically Dosage.
• Tropane Alkaloids should be avoided in patients with Glaucoma, prostatic hypertrophy, and Urinary Tract System diseases and also during Pregnancy.
• Tropane Alkaloids intoxications for humans result mainly from abuse (because of the hallucinogenic effects), consumption with Tropane Alkaloids containing plants, or accidental exposure.

• Tropane Alkaloids are found in plants of numerous families (especially Solanaceae, Erythroxylaceae, Convolvulaceae, Brassicaceae, and Euphorbiaceae, and they comprise mono-esters, di-esters, and tri-esters and carboxylated and benzoylated tropanes).
• Several of these Alkaloids occur as chiral structures due to the presence of a tropic acid residue attached to the ecgonine nucleus as an ester.
• The former occurs naturally in its R form; however, racemic mixtures may appear, especially during alkaline extraction (e.g., the formation of (+)-atropine from (-)-Hyoscyamine).
• Several acids are distinguished as being present in the tropane Alkaloids (including tropic, tiglic, acetic, isovaleric, isobutyric, benzoic, or anisic acids).