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Dr Azza Presentation1

VIEWS: 11 PAGES: 48

									           BY




Department of Pharmacognosy
    Faculty of Pharmacy
     Zagazig University
The CNS is the main co-ordinator of the body functions, being
responsible for:
     Consciousness
     Behavior
     Memory
     Recognition
     Learning
The most highly developed attributes of man such as:
        Imagination- Abstract reasoning - Creative thought.
It consists of two main parts:
    1. Brain → (in the skull)
    2. Spinal cord → (in the vertebral canal)
The CNS is responsible for conveying information from the outside
world to the body and Relaying massages from one part of the body to
another. This is done by the help of neurotransmitters.
They are chemicals that carry messages to nerve cells (neurons), and
help these massages jump their signals from cell to cell across gaps called
synapses.
               OH
                                                                  H
HO                        HO                                      N



                    NH2                      NH2
                                                    HO
                          HO                                              NH2
HO

     Norepinephrine              Dopamine                  Serotonin

If there is too much or not enough of a particular neurotransmitter, the
chemistry of the brain can be disturbed. This will affect:
     Mental function and emotional balance (stimulation, depression,
    anxiety,…etc.)
     Indeed, the entire body may be affected.
They act directly on the CNS by increasing the effectiveness of
excitatory synaptic signaling… or… by reducing central inhibition.
Manifestations of CNS stimulants include:
     Mild elevation in alertness
     Increased nervousness and anxiety
     Convulsions

               Classification of CNS Stimulants
             (With a Pharmacological Background)


   Psychomotor            Psychotomimetic            Convulsants
   Stimulants               Stimulants            and respiratory
                          (Hallucinogens)            stimulants
                                                    (Analeptics)
The have marked effect on mental function and behavior,
producing:
   Excitement and euphoria
   Reduced sensation of fatigue
   Increased motor activity
This class includes:
  I. Amphetamines
  II. Methylxanthines (caffeine, theobromine,..etc)
  III.Cocaine
  IV.Nicotine
Actions: Amphetamine and related compounds stimulates the entire
axis, cortex, brain stem and medulla.
                                      CH3

                                            Amphetamine
                                NH2
Effects:
    Increased alertness
    Decreased fatigue
    Depressed appetite
    Insomnia
Excessive use → convulsions
Mode of action:
    Elevation of the catecholamines transmitters (especially
   dopamine) in synaptic spaces, by releasing the intracellular stores of
   catecholamine. And also by
    Blocking MAO enzyme → High level of transmitters in the synaptic
   spaces.
                Mechanism of action of amphetamines
Actions: Xanthines Such as caffeine and theophylline (widely
used as drinks, tea, coffee, kola, …etc.). They stimulate the cortex
and other areas of the brain.
   Increase mental alertness
   Produce anxiety and tremors

Mode of action:
    Increase in cyclic adenosine monophosphate (cAMP)and
    cyclic guanosine monophosphate (cGMP).
  [By inhibition of phosphodiestrase, and blockade of adenosine
receptors]
Cocaine is an inexpensive, widely available, and highly
addictive drug that is currently abused and is found in coca
leaves.                  COOMe
            H3C
                  N
                           O
                                          Cocaine
                                   C6H5

                               O

Actions: It is a marked psychomotor stimulant causing:
   Acute increase in mental awareness
   Feeling of well-being and euphoria
   Hallucination, delusions and paranoia
   Increased motor activity
Excessive doses →Tremors and convulsions, followed by
Respiratory and vasomotor depression.
Mode of Action:
   Blockade of norepinepherine, serotonin and dopamine re-
   uptake.         Mechanism of action of cocaine
                                                              N

Nicotine is the most important pharmacological                        CH3

constituent of tobacco. It is second only after caffeine as            N
the most widely used CNS stimulant and is the second
after alcohol as the most abused drug.

Actions:                                                     Nicotine
    Some degree of euphoria, arousal and relaxation
    Improves attention, learning, problem solving and reaction time
High doses →
    Central respiratory paralysis
    Sever hypotension
Mode of Action:
    Nicotine causes excitation followed by inhibition of all synaptic and
   parasynaptic ganglia.
       •At low doses → ganglionic stimulation by depolarization of the
       postganglionic membrane.
       •At high doses →ganglionic blockade.
They are characterized by affecting thought, perception and mood,
without causing marked psychomotor stimulation or depression.
Effects:
     Distortion of perception and thoughts (becoming dream like).
     Bright,colourful changes in environment
     Incabability of normal decision making (it interferes with rational
    thought).
Classification
2.Psychotomimetic drugs with a chemical resemblance to known
1.Psychotomimetic drugs unrelated to known neurotransmitters e.g.:
     ∆9-tetrahydrocannabinol (THC): is the main constituent of
neurotransmitters e.g.:
     LSD (chemical derivative of lysergic acid,a loss of appreciation of
    cannabis. It produces euphoria and often of ergot).
     Psilocybin (obtained from a fungus).
    time and space.
     Mescaline (obtained from of THC iscactus). clear. ???
       The mechanism of action Mexican still not
     Mode of Action:
         They have serotonin (5-HT) agonist activity at presynaptic
           receptors in the midbrain, binding to both 5-HT1 and 5-HT2
           receptors.
This class comprises a diverse chemical class of agents ranging from
natural compounds e.g. strychnine and picrotoxin, to synthetic
compounds such as doxapram.
Picrotoxin: is a plant vomica): is an convulsions by blocking the action
Strychnine (from Nux toxin, it causesanaleptic stimulant.
of GABA (γ-aminobutyric acid).the spinal cord Causing → violent extensor
     Actions: It acts through
                                                    O
                                        O
    spasms that are triggered by minor sensory stimuli. H
                   O          O    H

     In small doses:        CH3                   CH3
        •Improvement in visual and auditory acuity.→ (tonic)
                     O                    O

     Mode of action: O CO OH                 O CO OH

        •Blocking the action of glycine (The main inhibitory transmitter
        acting on motoneurons).                 N
                                           H
                     H2C    CH3            H3C        CH3
                                                 OH

                       Picrotin            Picrotoxinin
                                                H     H
                          1           :         1
                                  Picrotoxin
                                           N
                                                        O
                             Strychnine
                                           O
Scientific names: Thea sinensis, Camellia
sinensis, Thea viridis Family Theaceae.
     Green tea: Prepared from the dried leaves.
     Black tea: Prepared from fermented and
    dried leaves.
Constituents:
    Caffeine (up to 4%) and smaller amounts of
   theophylline and theobromine.
    Polyphenols (tannins and flavonoids).
    B-vitamines and ascorbic acid.
             O                          O                   O
                        CH3                                           CH3
                                              H
   H3C                        H3C
                    N                         N                   N
         N                          N                  HN


                    N                         N                   N
     O       N                 O        N          O        N

             CH3                        CH3                 CH3

         Caffeine               Theophylline           Theobromine
Actions and uses:
    The CNS stimulation is mainly due to caffeine.
    Caffeine is the world's most popular drug, and is the only
   nonprescription stimulant approved by the FDA as either food or drug
   additive.
    Phenolics → Antioxidant properties.
    Tannins → Anti-diarrheal
Dosages:
     For stimulation: Boiling water + a teaspoon of tea, allow steep to for
    2min.
     For diarrhea: Steep for 10min.
Safety issues:
     Tea is quite safe stimulant drink (in moderate amounts).
     More than 5 cups/day (more than 300mg caffeine) may cause:
        •Impaired iron absorption →microcytic anemia.
        •Premature baby delivery.
During lactation → irritability and increased bowel activity.
Caffeine should be used carefully with people suffering from →
Hypertension, depression, anxiety, gastric or duodenal ulcers, or kidney
disorders.
Scientific names: Coffea arobica, and other
spp.: C. liberica and C. canephora. ( Fam.
Rubiaceae).


The part used: the dried seeds (beans).
    Prepared coffee: is the kernel of the
   dried ripe seeds.


Constituents:
    Caffeine (1-1.3%), theophylline and theobromine.
    Tannins, Fixed oil, and nicotinic acid.
Actions and uses:
    It is a psychomotor stimulant (caffeine), similar to tea.
Scientific name: Cola acuminate (Fam. Sterculaceae).
Part used: the seeds.
Constituents:
    Caffeine (up to 2.5%) and theobromine.
    Tannins and anthocyanins.
Actions and uses: CNS stimulant as tea.
Cola preparations: Cola dry ext.; Cola fluid ext. and Cola tincture



Common names: Cacao; Cacao beans; Cacao seeds;Theobroma.
Scientific name: Theobroma cacao L. (Fam. Sterculaceae).
Constituents:
    Theobromine (0.5-2.7%); caffeine (about 0.25%)
    Trigonolline, Fixed oil, Vol. oil.
Actions and uses:
    Theobromine has CNS stimulant effect similar to caffeine. But it is
   more potent diuretic and cardiac stimulant and coronary dilator than
   caffeine.
Common names: Gaurana past or gum;
Brazilian cocoa, zoom, Pasta guarana.
Scientific name: Paulinia cupana Kunth or P.
sorbilis L. (Fam. Sapindaceae)
Gaurana: is the dried paste made from the
crushed kernels by the help of water and starch
Constituents:
    Caffeine (up to 7%), theobromine and theophylline
    Tannins and saponins.
Actions and uses:
    resembles tea and coffee in its action
    It is used in the form of syrups, extracts and distillates as a source
   of caffeine in soft drink industry.
    As ingredient in herbal weight loss preparations in combination
   with Ephedra.
Actions and uses:Ma Huang; Brigham tea; Natural Ecstasy…etc.
Common names:
    Ephedrine Ephedra sinica and to amphetamine and causes CNS
Scientific name:is structurally relatedother spp.
   stimulation in a similar way to amphetamines through increasing the
Part used: The stems
   availability of endogenous neurotransmitters.
Active constituents:
Dosage: quantity of ephedra equivalent to is theephedrine/day.
    Alkaloids (0.5-2.5%), ephedrine 24mg major one,                    beside
Preparation: Crude powdered drug, and others.
   pseudoepherdrine, norephedrine tinctures; fluid extr.
Contraindications and precautions:
                 OH                                     OH

    In pregnancy → risk 3of uterine stimulation
                      CH                                          CH3

    In diabetic patients → hypoglycemic effects.
                    NH                                       NH
    In patientsHwith cardiac arrhythmias, angina, with history of cerebral
                 3C
                                                              2



   disease.                               Norpseudoephedrine
          Ephedrine
    Concomitant use with beta blockers and MAO inhibitors →risk of GI
                                               (Cathine)
   and CNS adverse effects
Scientific name: Catha edulis Forsk. (Fam. Celastraceae).
Part used: Fresh leaves and twigs.
Constituents:
    Cathinone1%, Norepseudoephedrine;
    Ephedrine…etc.               O

    Tannins, vol. oil.                     CH3



                                      NH2         Cathinone
Actions and uses:
    The CNS stimulation of khat is manly due to cathinone and
   norepseudoephedrine.
      (It shows amphetamine –like actions).
    Khat is manly used as a social drug through chewing or taken as
   an infusion.
    Khat is used in Germany to counter obesity.
Scientific name: Erythroxylom coca, and other e. spp, (Fam.
Erythroxylaceae)
Part used: The leaves.
Constituents:
     Alkaloids cocaine (0.7-1.5%), together with cinnamyl cocaine, and
    α- and β- truxillines.
     Vol. oil, Flavonoids, Tannins, Vit. A and B2 and minerals.
Toxicity: Chronic toxicity appears as follows:
                                  COOMe
     Running or H3C  bleeding mucous membranes.
                          N
     Decreased appetite, Malnutrition.         Cocaine
                                     O
     Irritability, restlessness, and paranoia.
                                          C6H5


     Can lead to full blown psychosis. O

Actions and uses: term heart disease.
     Possible long
     It is a stimulant and local by addicts:
Current trends in cocaine use anesthetic drug (Cocaine).
     Orally:taken illegally as a narcotic, stimulant drug. (Extremely
       It is Chewing of the leaves.
     Inhalation: Inhaled into the nasal cavity.
    addictive).
     Injection: IV or hypodermic (Cocaine HCl).
     Smoking: As cigarettes.
                                                          N
Scientific name: Nicotiana tabaccum (Fam.                           CH3
Solanaceae).
The Part used: The leaves.                                         N

Constituents: Alkaloids (nicotine is the most
important)                                               Nicotine
Actions and Uses:
     It is a psychomotor CNS stimulant (some degree of euphoria, and
    arousal, as well as relaxation, and improves learning, problem
    solving and reaction time).
     It is grown mainly produce smoking or smokeless tobacco.
     Dried leaves make a good insecticide.
     It is no longer used medicinally.
Smokeless tobacco:
     Prepared from the same botanical source, and usually flavored
    with sugar or artificial sweeteners.
Common ways of consumption:
     In Europe → Snuffing.
     In USA and other countries → placing in the buccal area between
    the gum and cheek, followed by swallowing the resultant saliva.
                                                                          H
                                                                          N
Common         names:      Mexican      hallucinogenic
                                                                                 H3C
mushroom, flesh of the gods.
Scientific name: Psilocybe mexicana                          O
                                                                                       N
                                                                                            CH3

Active     constituents:    Tryptamine      derivatives HO   P
                                                                   O


psilocybin and psilocin (related to serotonin).               OH

Actions: It resembles LSD in its effects.                              Psilocybin




                                                              H3CO

Common names: Mescal; Mescal buttons,
                                                                                           NH2
Anhalonium                                                    H3CO
Scientific name: The cactus Lophophora williamsii
                                                                         OCH 3
 (Fam. Cactaceae).
Active constituents: Alkaloids; the cheive one is
mescaline.                                                             Mescaline
Actions: It resembles LSD in its effects.
Common names: Marijuana or Marihuana (leaves and flowering
tops); Kif (resinous materials and flowering tops mixed with leaves);
Bang (dried mature leaves); Banji, Hemp, Cannabis, Shisha (entire
plant); Hashish (resinous material with flowering tops).
Scientific name: Cannabis sativa (Fam. Cannabinaceae).
Constituents:
     More than 420 compounds (Alkaloids, steroids, Vol. oil).
     The most important is THC (delta 9-tetrahdrocannabinol).
     Cannabis is the only plant that contains THC (1-4%).
Actions and uses:                                          CH3

    In small doses → Euphoria; distortion of time
   and distance; and visual and auditory                                OH
                                                            H
   hallucinations
    In large doses → Impairs reaction time, motor                H
                                                     H3C
   coordination, visual perception and panic
                                                      H3C         O          C5H11
   reactions.
Other hallucinogens includes                                         THC
    The fungus Amanita muscarina and Nutmeg.
Scientific name: Strychnos nux-vomica (Fam. Loganiaceae).
Constituents:
    The seed contains alkaloids (up to 3%); Strychnine is responsible
   for the pharmacological effects.
Actions and uses:
    Strychnine is a long-lasting stimulant of the nervous system.
    Strychnine is a useful nervous system tonic.  H
                                                        N

    It is recommended as a tonic for the elderly.
    The effect of the whole drug (Nux vomica) is slower H onset than
                                                        H     in
   strychnine, but more uniform and thus minimizing induction of the
   CNS convulsions.                                N
                                                               O
Preparations:
                                                  O
    Strychnine tincture: 10-20 drops, three times a day. Strychnine
    Sample prescriptions:
        •Tinct. N. vomica 5ml + tinct. Valerian 15ml, 20 drops 3 times/day.
        •Tinct. N. vomica 10ml + tinct. Gentian 20ml, 20 drops in water
        before meals.
Common names: Fishberry; Fish killer, Indian berry.
Scientific name: Anamerita cocculus, A. Paniculata, Menispermum
cocculus, M. suberosus (Menispermaceae).
Constituents:
    Bitter toxic principle (Picrotoxin).
    Alkaloids and fixed oil.
                                      O            O                   O        H
Actions and uses: O                           H

                                                                      CH
    Picrotoxin is a stimulant for theO management of morphine
                         CH3                  3

                       O
   poisoning.                    O   CO   OH                 O    CO       OH


    In experimental models of CNS stimulation.
    Cocculus is sold commercially as a remedy for parasites, as
                           H2C        CH3              H3C            CH3
                                                                 OH
   astringent, antifungal, and anthelmintic.
                        Picrotin             Picrotoxinin
    It was considered as an official remedy for epilepsy, but no longer
                            1           :         1
   used because of sever toxicity. Picrotoxin
Depression is a pervasive mood altering illness affecting energy, sleep,
appetite, libido and the ability to function.
Signs and Symptoms:
    Intense feeling of sadness, hopelessness, and despair.
    Inability to experience pleasure in usual activities.
    Initial complains are often physical:
        •Fatigue
        •Headache.
        •Insomnia.
        •Gastrointestinal disturbance.
    Followed by:
        •Anorexia – Weight loss – Bade taste in the mouth – inactivity –
        loss of sexual desire – loss of joy in living – Guilt is a unique
        symptom
Mania is characterized by opposite behavior:
    Enthusiasm, rapid thought and speech patterns.
    Extreme self-confidence and impaired judgment.
Risk factors and causes:
    Grief (loss of a loved one through death or divorce).
    Interpersonal disputes (conflict with a family member or a
   superior).
    Serious illness.
    Lack of social support system.
    Physical, sexual, or emotional abuse.
    Family history of depression.
    Major events that occur in everyone's life, such as graduation, job
   change , getting married, retirement.
Treatment Options:
    Pharmacotherapy (modern medicines),
    Psychotherapy.
    Yoga, exercise, massages.
    Hospitalization if suicide is possible.
    Natural antidepressants (herbal treatment).
    Nutritional support
              Mechanism of Action of Antidepressants


1. Inhibition of re-uptake of               2. Inhibition of MAO.
     neurotransmitters.
Scientific name: Hypericum perforatum L., and other spp. (about 370);
Fam. Hypericaceae.
Used Part: The flowering tops.
Constituents:
    Naphthodianthrones (0.05-0.6%): Hypericin, pseudohypericin, and
   others.                                          OH O     OH

    Flavonoids (7-12%) and phenolics (Hyperforin).
    Carotenoids, vol. oil, sterols.
                    .         .
                                                      HO                              CH 2R

                                                      HO                              CH3


                O             OH
                                      .

    .                                         .
                                          .                    OH      O     OH
                                                                                  R
                    O             O
        .                                         .
                .
                        CH3                                Hypericin              H
                                      Hyperforin
            .                                              Pseudohypericin        OH
Uses and Mode of Action:
    St. John's Wort is used for mood disorders; particularly depression.
    Hypericin→ was thought to act as a MAO inhibitor.
    Hypericin→ Proved to be selective serotonin reuptake inhibitor
   (SSRI). (50% inhibition).
    Hypericin→Inhibits COMT (catechol-0-methyltransferase); an
   enzyme capable of destroying biological amines.
    Hyperforin →Potent inhibitor of serotonin, noreadrenaline and
   dopamine reuptake.
The advantage of this combination of actions is fewer side effects,
because the total response is not due to a single type of activity.
Preparations and wort formulations available in USA:
 Some St. John's Dosages:
    Extr. Of St. John's Wort is standardized to contain 0.4% hypericin.
    Tablets:
    Dried flowers : 2-4mg → Cont. stand.. extr.
       •Movana® and Kira® tpd.
    Tincture (1:5):®3-6ml tpd. + Kava kava.
       •One A Day →Hypericin
    Fluid extract (1:1):Hypericin +ginseng.
       • Harmonex®→ 1-2ml tpd.
    Standardized solid (dry powder) extr. (0.14% hypericin): 600mg tpd.
       • Sundown® Herbal→ Hypericin + ginkgo biloba + ginger.
Scientific name: Piper methysticin (Fam. Piperaceae).
Parts used: Rhizome and root.
Constituents:
    Kava lactones (3-20%): Kawain (kavain); dihydrokavain ..etc.
    Chalcones: Flavokawains A and B.
    Some minor alkaloids.
Actions and uses:
                OCH
                 3                      OCH                         OCH
                                           3                          3

    To relieve anxiety and stress.
    To exhibit sedative, analgesic and muscle relaxant effects.
    These neurologic effects of kava are attributed to the kavalactones O
                O   O
                                        O     O
                                                  O
                                                                    O

   it contains.                                   O

Traditional and current use: Dihydrokavain
  Kavain (Kawain)                                        Methysticin
    Aphrodisiac – narcotic – antiseptic – pain killer
Mode of action:
    The mechanism of CNS effects of Kava is not quite clear, however
   it is suggested that Kavalactones:
    Enhance the GABA binding to receptors.
    Inhibit uptake of noradrenaline.
Dosage and preparations:
    Kava tablets (1.2-1.8%g, stand. To contain 60mg lactones); 1 tablet
   2-4 times/day.
    Dried root and liquid extract…etc.
Side effects and toxicity:
    No side effects with stand. Kava preparations at recommended
   levels.
    Kava may interfere with dopamine and worsen Parkinson's
   patients.
    Prolonged use (months or year) → Kava dermopathy (scaly
   eruption of skin).
    Kava is contra indicated in pregnancy and nursing.
Scientific name: Ginkgo biloba (Fam. Ginkgoaceae).
Constituents:
       Flavonoids (24%), dimeric bioflavones.
       Terpenes (6%), ginkgolides.
       Small amounts of steroids and organic acids.
                                                                                           H
                                   OR 1
                                          OH                 H3C                  O                 O
                                                                       HO
 R2O                O
                                                                                      CO                     O

                                                         O
                                                                                      O
                               O                    OH
                                                                   O                                  OH
            OH      O                                                                               C(CH 3)3
                                               O                        H
                                                                                R1
                                                                                               R2
                   R3O

                         R1    R2              R3                                      R1               R2
       Bilobetin         CH3   H               H                   Ginkgolide A        H                H
       Ginkgetin         CH3   CH3             H                   Ginkgolide B        OH               H
       Isoginkgetin      CH3   H               CH3                 Ginkgolide          OH               OH
       Sciadopitysin     CH3   CH3             CH3            C
Actions and uses:
Commercial preparations:
    G. biloba ,extract tablets. is used to treat →Cognitive deficiency
    Gingoba® 40mg (GBE)
   (caused by, inadequate blood flow and nerve degeneration in the brain
    Ginkgo® 40 mg , tab.; caps.
   causing →short-term memory loss and confusion.
    Ginkai® , 50mg tab.
    GBE improves cerebral bloodand garlic) cap.
    Ginkgogin® (ginkgo, ginseng, circulation.
    GBE flavonoids, and bilobalide reduce harmful brain damage
    Bioginkgo® , 50mg tab.
   (antioxidant).
Contraindications:
    GBE ginkgolides are potent platelet activating factor (PAF) inhibitor
    Patients taking anticoagulant therapy, as it inhibits PAF.
   (prevent thrombosis).
    All these combined effects reduce brain damage and treat cognitive
   deficiency.
Toxicity:
    Ginkgolic acids cause allergic reaction and are normally removed
                                         OH
   during preparation of GBE.                           Ginkgolic acids
                                                       R= C13H27 (C13:0)
Dosages:                                       COOH
                                                       R= C15H31 (C15:0)
    Daily dose of GBE → 120-240 mg taken in 2-3 R= C15H29 (C15:1)
                                                       separate doses.
                                                R
                                                      R= C17H31 (C17:2)
Some herbs are used to treat restlessness and sleep
disturbances, and their efficacy as antidepressant is largely
unproved. They are frequently used in combination with anti-
stress drugs including:
    Valerian: sedative, tranquilizer and in insomnia.
    Ginseng: helps body to adapt to stress.
    Hops:       Sedative and relaxant.
    Passion flower: Sedative, tranquilizer and aids sleeping.
    Lavender: Calming and relaxing effects.
Nutritional treatment includes:
    1. Supplementation with amino acids.
    2. Supportive treatment with vitamins and minerals.
1.Amino acid supplements:
     L-Tyrosine and L-phenylalanine are precursors to the biogenic
    neurotransmitters. So are helpful in treating depression.
2.Vitamins: Vitamin deficiency can cause depression.
    i. Vit. B6: is a co-factor in serotonin and norepine-pherine synthesis.
    ii. Vit C: is a cofactor in serotonin synthesis.
    iii.Folic acid and/or Vit B12 deficiency cause depression, their
    administration result in dramatic improvement.
3.Minerals:
    i. Magnesium: deficiency →depression.
           •Nutritional support →improves mood in patient with depression.
    ii. Chromium: →Helps stabilize mood changes associated with
    hypoglycemia.
 "Usually a combination of
relaxation techniques,
therapeutic massage,
nutritional support, and herbs
provide the greatest relief of
depression".
I wish you all peaceful and enjoyable life




                       CNS Stimulant

                      or Antidepressant

								
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