Awatif B. Al-Backer

Awatif B. Al-Backer

pharmacological experiments

In vitro

* Isolated tissue

* Allow to study the MOA & the potency of the drug

In vivo

* Whole animal or

intact animal* Easier to study the clinical effect of drugs

Awatif B. Al-Backer

Anatomy of The Brain

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Anatomical features of CNS

1. Cerebellum

2. Medulla oblengata Regulate vital visceral

activities

3. Spinal cord For all reflexes

Equilibrium & coordination of

movement

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Classification of Drugs Acting on CNS

Drugs acting on CNS

CNS stimulants

CNSdepressants

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CNS Stimulants

They 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.

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General Signs & Symptoms of CNS Stimulation

1. ↑ Heart rate2. ↑ Respiratory rate3. Instability & restlessness4. Muscle twitching (tremors) 5. Hair erection6. Convulsion

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Classification of CNS Stimulants According to Their Site of

action

1. Cerebral stimulants2. Brain stem ( Pons & medulla)

stimulants3. Spinal cord stimulants

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Cerebral Stimulants

Examples Caffeine & Cocaine

MOA 1. It inhibits phosphodiesterase enz. → ↑ cAMP 1. ↑calcium in CNS & heart

2. ↓calcium in Smooth muscles

2. A2 receptors antagonist → CNS stimulation & smooth muscles relaxation

Signs of stimulation

1. Hair erection

2. Tail erection (onset of action)

High Dose epileptiform type of convulsion

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Medullary Stimulants

Ex. Picrotoxin

MOA: (of picrotoxin)1. It inhibits the presynaptic inhibition decrease GABA.2. Non competitive GABAA receptors blocker which is a chloride dependent no hyperpolarization excitation

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Medullary Stimulants: Cont.

Signs produced by medullary stimulants:In large doses they cause CLONIC

CONVULSION

Characteristics of clonic convulsion:1. Asymmetric 2. Coordinated 3. Intermittent4. Spontaneous in origin5. It starts as clonic then converted into

tonic-clonic & finally to tonic6. Removed by decapitation

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Spinal Cord Stimulants

Ex. Strychnine

MOA: It blocks postsynaptic inhibition by blocking the action of glycine in spinal cord

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Signs produced by spinal cord stimulants:In large doses strychnine causes TONIC CONVULSION

Characteristics of tonic convulsion:1- Symmetric2- Non-coordinated 3- Continuous 4- Reflex in origin5- Characteristic arched back (Opisthatenous posture)6- Removed by pithing

Spinal Cord Stimulants: Cont.

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Differences Between Clonic & Tonic Convulsions

Clonic Tonic

- Produced by ↑dose of medullary stimulants- Asymmetric - Coordinated - Spontaneous - Intermittent- Removed by decapitation

- Produced by ↑dose of spinal cord stimulants- Symmetric- Non-coordinated - Reflex in origin - Continuous- Removed by pithing

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Lab work

Drug Conc.

Dose ROA

Caffeine 1% 100 mg/kg

IP

Strychnine

0.1%

5 mg/kg

IP

Picrotoxin

0.5%

25 mg/kg

IP

Calculation

Wt = 30 gm Conc=0.1% Dose=100 mg/kg1- Dose in (mg) 100 mg → 1 kg i.e. 100 mg → 1000 gm x → 30 gm x = 30 * 100 = 3 mg 10002- Dose in (ml) 0.1%= 0.1 gm → 100 ml i.e. 100 mg → 100 ml 3 mg → x x = 3 * 100 = 3 ml 100