Awatif B. Al-Backer

pharmacological experiments In vitro * Isolated tissue Allow to study the MOA & the potency of the drug * 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

Awatif B. Al-Backer Anatomical features of CNS 1.Cerebellum 2.Medulla oblengata Regulate vital visceral activities 3. Spinal cord For all reflexes Equilibrium & coordination of movement

Awatif B. Al-Backer Classification of Drugs Acting on CNS Drugs acting on CNS stimulants CNS depressants

Awatif B. Al-Backer 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.

Awatif B. Al-Backer General Signs & Symptoms of CNS Stimulation 1.↑ Heart rate 2.↑ Respiratory rate 3. Instability & restlessness 4. Muscle twitching (tremors) 5. Hair erection 6. Convulsion

Awatif B. Al-Backer Classification of CNS Stimulants According to Their Site of action 1.Cerebral stimulants 2.Brain stem ( Pons & medulla) stimulants 3.Spinal cord stimulants

Awatif B. Al-Backer Cerebral Stimulants Examples Caffeine & Cocaine MOA 1. It inhibits phosphodiesterase enz. → ↑ cAMP It inhibits phosphodiesterase enz. → ↑ cAMP 1. ↑calcium in CNS & heart 2. ↓calcium in Smooth muscles A2 receptors antagonist → CNS stimulation & smooth muscles relaxation 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

Awatif B. Al-Backer 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

Awatif B. Al-Backer Medullary Stimulants: Cont. Signs produced by medullary stimulants: 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

Awatif B. Al-Backer Spinal Cord Stimulants Ex. Strychnine MOA: It blocks postsynaptic inhibition by blocking the action of glycine in spinal cord

Awatif B. Al-Backer Signs produced by spinal cord stimulants: In large doses strychnine causes TONIC CONVULSION Characteristics of tonic convulsion: 1- Symmetric 2- Non-coordinated 3- Continuous 4- Reflex in origin 5- Characteristic arched back (Opisthatenous posture) 6- Removed by pithing Spinal Cord Stimulants: Cont.

Awatif B. Al-Backer Differences Between Clonic & Tonic Convulsions Clonic Clonic Tonic 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

Awatif B. Al-Backer Lab work Drug Drug Conc. Conc. Dose Dose ROA ROACaffeine 1% 1% 100 mg/kg 100 mg/kg IP IP Strychnine 0.1% 0.1% 5 mg/kg 5 mg/kg IP IP Picrotoxin 0.5% 0.5% 25 mg/kg 25 mg/kg IP IP

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