Submitted by Group 8

Submitted to sir Azmat rasheedCerebral , medullary and spinal

stimulant

Group members

*M.Asad

*Ghous Jamil

*Anum Tariq

*Memona Kalsoom

*Shiza Shakoor

Presented to Sir Azmat

*

Basic Description of CNS_PNS.

Understanding of the Classification of CNS STIMULANT The Cerebral- Stimulant agents

The Medullary or M.O - Stimulant agents

The Spinal Stimulant agents

*

*The nervous system can be classified into

*The Central Nervous System (CNS)

*Brain and spinal cord

*The Peripheral Nervous System (PNS (

*The nervous system outside of the brain and spinal cord

*

*

*Drugs acting on

CNS

CNS

stimulantsCNS

depressants

*Remember CNS

depressant drugs..??

*

*Definition and introduction

are drugs which increase the muscular (motor) and the

mental (sensory) activities

Their effects vary from the increase in the alertness

and wakefulness (as with caffeine)

To the production of convulsion ( as with strychnine)

or death due to over stimulation

*

General Signs & Symptoms of CNS Stimulation

•↑ Heart rate

•↑ Respiratory rate

• Instability

•Tremors

•Hair erection

•Convulsion

*

According to:

• Structural similarities

or

• Site of therapeutic action in the central nervous

system (CNS)

or

•Major therapeutic usages

*

*1- Block neurotransmitters reuptake (Most reuptake

inhibitors affect either NE or 5- HT(Serotonin) : Cocaine

*2- Promote neurotransmitters release : Amphetamine

*3- Block Metabolism - MAO inhibitors (monoamine

5tttttoxidase):ex. Phenelzine

*4. antagonize the effect of inhibitory neurotransmitter:

Picrotoxin & Strychnine

*

*They can be divided based on their site of action:

1.Cerebral stimulants or cortical stimulant (amphetamines)

2.Medullary stimulants (picrotoxin)

3.Spinal stimulants (strychnine)

1)

*Cerebral, or psychic, stimulants act on the central nerv

ous system and provide a temporary

sense of alertness and well

being as well as relief from fatigue.

*They are further classified as

a. Psychomimetics

- Amphetamine and related drugs

- Cocaine

b. Methylxanthines

a.

*Psychomimetics includes following agents

i. Amphetamine

ii. Methylphenidate

iii. Methamphetamine

iv. Cocaine HCl

Mechanism of action of psychomimetics

They act primarily by releasing NA and DA in the brain. They block NA

reuptake, inhibits MAO and has direct effect on receptors.

I. Amphetamine

*Amphetamines are chemically related to adrenaline.They are sympathomimetic drugs which mimic the effect of stimulation on the nervous system by increasing the levels of dopamine.uses

* Amphetamines were initially used to treat narcolepsy and in WW II were used by soldiers to combat fatigue. to improve the performance of soldiers, military pilots and others who need to remain alert under extremely fatiguing conditions.

Adverse effect

*With prolonged use, they are neurotoxic, causing degeneration of amine-containing nerve terminals and eventually cell death.

• Regular use can lead to both tolerance & dependence.

II. Methylphenidate

*Methylphenidate (MPH) is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder, or ADHD.

*It is also one of the primary drugs used to treat the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome.

*The drug is seeing early use to treat cancer-related fatigue

Indications

1- ADHD

2- Narcolepsy

3- Treatment-resistant depression

4- Appetite suppressant

5- Antidepressant augmentation

Contraindication

Use of tricyclic antidepressants: (e.g. desipramine), as methylphenidate may dangerously increase their plasma concentrations, leading to potential toxic reactions (mainly, cardiovascular effects).

iii.Methamphetamine

*Methamphetamine , also known as methylamphetamine, N-

methylamphetamine or desoxyephedrine, is a psychostimulant and

sympathomimetic drug.

Clinical uses

*It is considered a second line of treatment, used when amphetamine

and methylphenidate cause the patient too many side effects. It is also

used illegally for weight loss and 11 to maintain alertness, focus,

motivation, and mental clarity for extended periods of time, and for

recreational purposes.

Side effects

*Methamphetamine has the potential to cause addiction.

*Methamphetamine is a potent neurotoxin, shown to cause

dopaminergic degeneration.

*Methamphetamine addicts may lose their teeth abnormally quickly, a

condition known as "meth mouth".

iv. Cocaine

*Cocaine increase, mental alertness & produce a feeling of wellbeing &

euphoria that is similar to that caused by amphetamine like

amphetamine cocaine can produce hallucinations, delusion & paranoia

cocaine increases motor activity & at high doses causes tremors,

convulsion & followed by respiratory & vesomotor depression.

Uses

*Cocaine has a local anesthetic action for the therapeutic use of cocaine,

cocaine is applied topically as a local anesthetic for eye, ear & nose &

throat surgery

Adverse effect

*cocaine stimulation of CNS is followed by a period of mental

depression.

*Physical dependence after only single use

b.

*Various beverages, particularly tea, coffee and cocoa, contain

methylxanthines, to which they owe their mild central stimulant

effects. (theophylline, caffeine, theobromine) are the drugs included

in metylxanthines

MOA

*methylxanthines (especially theophylline) inhibit

phosphodiesterase, which is responsible for the intracellular

metabolism of cAMP (Ch. 3). They thus increase intracellular

cAMP and produce effects that mimic those of mediators that

stimulate adenylyl cyclase. Methylxanthines also antagonise many

of the effects of adenosine, acting on both A1 and A2 receptors

*

Clinical use

*witH aspirin in some preparations for treating headaches and

other aches and pains,

*Theophylline (formulated as aminophylline) is used mainly as

a bronchodilator in treating severe asthmatic attacks

Side effects

*High doses of caffeine cause epileptiform type of convulsion

*Nervousness,insomnia, tremors

*withdrawa

2)

*They are also called as analeptics Analeptics are general CNS

stimulants; they stimulate vitally important centers (respiratory

and vasomotor) of the brain. The primary medical use of these

drugs is as an anesthetic recovery tool or to treat

emergency respiratory depression.hense they are also called as

repiratory stimulant

*Medullary stimulant includes

a. Picrotoxin

b. Doxapram

c. Pentylenetetrazole or cardiazole

a. Picrotoxin

Picrotoxin is a toxin obtained from the seeds of the shrub Anamirta

cocculus. It is used as a central nervous system stimulant, antidote,

convulsant, and GABA (gamma aminobutyric acid) antagonist.

*MOA

Picrotoxin antagonizes the GABAA receptor channel directly, which is

a ligand-gated ion channel concerned chiefly with the passing of

chloride ions across the cell membrane. Therefore picrotoxin prevents

Cl- channel permeability and thus promtes an inhibitory influence on

the target neuron.

*Uses

it is most often used as a research tool, it has been used as a CNS

stimulant and an antidote in poisoning by CNS depressants, especially

barbiturates ,for relieving respiratory distress

b.Doxapram

Doxapram hydrochloride (marketed as Dopram, Stimulex or

Respiram) is a respiratory stimulant. Administered intravenously,

doxapram stimulates an increase in tidal volume, and respiratory rate.

MOA

Doxapram stimulates chemoreceptors in the carotid bodies of the

carotid arteries, which in turn, stimulates the respiratory centre in

the brain stem.

Uses

stimulate the respiratory rate in patients with respiratory failure. It

may be useful for treating respiratory depression in patients who have

taken excessive doses of drugs such as buprenorphin, also used for

recovery after anesthesia

c. Pentylenetetrazole or cardiazole

Pentylenetetrazol, also known as pentylenetetrazole,

metrazol, pentetrazol (INN), pentamethylenetetrazol,

Corazol, Cardiazol or PTZ, is a drug formerly used as a

circulatory and respiratory stimulant

MOA

It is specifically a GABA-a receptor antagonist it acts at the

picrotoxin (PTX) site of the gamma-aminobutyric acid type A

(GABA(A)) receptor

Side effects of medullary stimulant

In large doses they cause CLONIC CONVULSION

Characteristics of clonic convulsion:

1- Asymmetric

2- Coordinated

3- Intermittent

4- Spontaneous in origin

5- It starts as clonic then converted into tonic-clonic & finally to tonic

6- Removed by decapitation

Characteristic of chronic convulsions

1- Symmetric

2- Non-coordinated

3- Continuous

4- Reflex in origin

5- Characteristic arched back (Opisthatenous posture)

6- Removed by pithing

*Treatment of Strychnine Poisoning

(1) Remove/reduce external sensory stimuli

(2)Diazepam or Clonazepam I.V. or

(3) Nitrous oxide by inhalation to depress CNS and stop convulsions which can be fatal

3.Spinal cord stimulant includes strychinne strychnine is a naturally occurring alkaloid found in seeds from the plant Strychnos nox-vumica

Site of action

*Spinal cord

Mecahnism of action

*Strychnine is an antagonist of glycine, Strychnine competitively and reversibly the inhibitory neurotransmitter glycine at postsynaptic neuronal sites in the spinal cord

*Side effects

In large doses strychnine causes TONIC CONVULSION and causes strychine poisning

*

*Katzung Basic and clinical pharmacology

*Rang and Dales pharmacology 7th edition

*Good man and Gillman manual of

pharmacology