الادوية المؤثرة على الجهاز العصبي المركزية وكذلك مقدمة عن الجهاز والعصبي المركزي والنواقل العصبية

1. PTP 546
Module 10
Central Nervous System Pharmacology
Jayne Hansche Lobert, MS, RN, ACNS-BC, NP
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Lobert

2. CNS Pharmacology
Sedative-Hypnotic Agents
• Benzodiazepines
– Ex: Triazolam (Halcion)
– Ex: Temazepam (Restoril)
– Action: increases the inhibitory effects at CNS
synapses that use the neurotransmitter GABA
– Therapeutic Effect: decrease the level of arousal in the
individual relaxation and sleep
– Side Effects: drowsiness, dizziness, dry mouth, sore
throat, muscular incoordination, cardiovascular and
respirator depression
– Note: tolerance potential; physical and psychological
dependence abuse potential
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Lobert

3. CNS Pharmacology
Sedative-Hypnotic Agents
• Nonbenzodiazepines: Barbiturates
– Ex: Pentobarbital (Nembutal)
– Ex: Secobarbital (Seconal)
– Action: potentiates the inhibitory effects of GABA
– Therapeutic Effect: effective sedative-hypnotic
effect
– Side Effects: sedation, drowsiness, lethargy,
hangover effect
– Note: Tolerance; physical and psychological
dependence; abuse potential
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Lobert

4. CNS Pharmacology
Sedative-Hypnotic Agents
• Nonbenzodiazepine: Newer Agents
– Ex: Zolpidem (Ambien)
– Action: increased effectiveness of GABA binding
increased inhibition of GABA
– Therapeutic Effect: less CNS arousal sleep
promotion
– Side Effects: significantly less side effects of
hangover, drowsiness, fatigue
– Note: abuse potential remains
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Lobert

5. CNS Pharmacology
Antianxiety Agents
• Benzodiazepines
– Ex: Alpazolam (Xanax); Diazepam (Valium)
– Ex: Clonazepam (Klonopin); Lorazepam (Ativan)
– Action: potentiates the inhibitory effects of GABA
– Therapeutic Effect: rapid treatment of anxiety,
reduction of anxiety associated skeletal muscle
tension
– Side Effects: sedation, abuse potential,
psychomotor impairment, rebound anxiety with
abrupt withdrawal
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Lobert

6. CNS Pharmacology
Antianxiety Agents
• Non-Benzodiazepine
– Ex: Buspirone (BuSpar)
– Action: gradually increases serotonin in CNS
– Therapeutic Effect: treatment of long term &
chronic anxiety, obsessive compulsive
disorder(OCD), panic disorders
– Side Effects: less psychomotor impairment and
less sedation; less abuse potential, restlessness,
dizziness
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Lobert

7. CNS Pharmacology
Antidepressant Agents
• Monoamine Oxidase Inhibitors (MAO)
– Ex: Isocarboxazid (Marplan)
– Ex: Tranylcypromine (Parnate)
– Action: inhibits an enzyme directly increases
neurotansmitter activity at synapses
– Therapeutic Effects: treatment of major depression
that not responsive to SSRI’s and TCA’s
– Side Effects: orthostatic hypotension, various food and
drug interactions hypertensive crisis, coma, death
– Note: must avoid foods with tyramines avocado,
bananas, yogurt, red wines, pepperoni, salami; must
have an awareness of drug interactions
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Lobert

8. CNS Pharmacology
Antidepressant Agents
• Tricyclic antidepressant (TCA)
– Ex: Amitriptyline (Elavil)
– Ex: Imipramine (Tofranil)
– Action: blocks the reuptake of serotonin and
norepinephrine
– Therapeutic Effects: treatment of major
depression
– Side Effects: orthostatic hypotension,
constipation, dry mouth, urinary retention,
blurred vision, sedation, drowsiness
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Lobert

9. CNS Pharmacology
Antidepressant Agents
• Selective Serotonin Reuptake Inhibitors (SSRI)
– Ex: Sertraline (Zoloft); Citalopram (Celexa)
– Ex: Paroxetine (Paxil); Fluoxetine (Prozac)
– Action: inhibits the reuptake of serotonin
– Therapeutic Effects: treatment of depression
– Side Effects: dry mouth, nausea, headache,
fatigue, sexual dysfunction, insomnia
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Lobert

10. CNS Pharmacology
Antidepressant Agents
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
– Ex: Duloxetine (Cymbalta)
– Ex: Venlafaxine (Effexor)
– Ex: Bupropion (Wellbutrin)
– Action: primarily inhibits serotonin and
norepinephrine reuptake
– Therapeutic Effects: relief of major depressive
symptoms
– Side Effects: insomnia, tremors, hypertension or
orthostatic hypotension, agitation, blurred vision
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Lobert

11. CNS Pharmacology
Bipolar Agents
• Lithium (Eskalith)
– Action: alters cation transfer inhibits excitatory
neurotransmitters
– Therapeutic Effect: treatment, maintenance and
prophylaxis of mania; stabilization of moods
– Side Effects: headache, lethargy, fatigue, memory loss,
dry mouth, muscle weakness, tremors, leukocytosis,
ataxia, tremors
– Note: therapeutic blood level 0.6-1.5 meq/L; lithium is
now typically prescribed with antiseizure drugs and
other mood stabilizers; consistent sodium dietary
intake is necessary
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Lobert

12. CNS Pharmacology
Antipsychotic Agents
• Traditional Antipsychotics: Phenothiazines
– Ex: Chloropromazine (Clozaril;Thorazine)
– Action: blocks dopamine in CNS; has significant
anticholinergic and alpha-adrenergic blocking
activity
– Therapeutic Effect: second line treatment of
psychoses and schizophrenia
– Side Effects: sedation, extrapyramidal effects,
anticholinergic effects, neuroleptic malignant
syndrome
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Lobert

13. CNS Pharmacology
Antipsychotic Agents
• Atypical Antipsychotics: Newer Generation
– Ex: Risperidone (Risperdal);Quetiapine (Seroquel)
– Ex: Aripiprazole (Abilify); Olanzapine (Zyprexa)
– Ex: Haloperidol (Haldol)
– Action: antagonizes dopamine and serotonin; inhibits
alpha adrenergic receptors
– Therapeutic Effect: antipsychotic, mood stabilizer in
schizophrenia, bipolar
– Side Effects: orthostatic hypotension, sedation,
dizziness, weight gain, anticholinergic effects; yet less
extrapyramidal side effects; less NMS
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Lobert

14. CNS Pharmacology
Antipsychotic Agents
• Side Effects
– Acute Dystonic Reactions
• Facial grimacing, involuntary eye and muscle movements
– Akathisia
• Restlessness, difficulty sitting still, urge to move about
– Pseudo Parkinsonism
• Tremor, pill rolling, rigidity, salivation, shuffling gait, mask like face,
motor retardation
– Tardive Dyskinesia
• Protrusion of tongue, puffing of cheeks, chewing movements,
involuntary movements of extremities or trunk
– Neuroleptic Malignant Syndrome
• Fever, respiratory distress, tachycardia, convulsions, diaphoresis,
hyer or hypotension, pallor, severe muscle stiffness
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Lobert

15. CNS Pharmacology
AntiSeziure Agents
• Treatment of Seizures
– Barbiturates
• Ex: Phenobarbital (Phenobarb)
– Benzodiazepines
• Ex: Diazepam (Valium)
– Carboxylic Acids
• Ex: Valproic Acid (Depakote)
– Hydantoins
• Ex: Phenytoin (Dilantin)
– Iminostilbenes
• Ex: Carbamazepine (Tegretol)
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Lobert

16. CNS Pharmacology
AntiSeziure Agents
• Barbiturates
– Ex: Phenobarbital (Phenobarb)
– Action: potentiates the inhibitory effects of GABA
– Therapeutic Effect: all types of seizures
– Side Effects: highly sedative side effects,
drowsiness, dizziness, ataxia
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Lobert

17. CNS Pharmacology
AntiSeziure Agents
• Benzodiazepines
– Ex: Diazepam (Valium)
– Action: potentiates inhibitory effects of GABA
– Therapeutic Effect: acute treatment of status
epilepticus
– Side Effects: respiratory depression, sedation,
ataxia
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Lobert

18. CNS Pharmacology
AntiSeziure Agents
• Carboxylic Acids
– Ex: Valproic Acid (Depakote)
– Action: unclear increases CNS GABA
concentrations
– Therapeutic Effect: treatment of absence seizures,
secondary agent for tonic- clonic epilepsy
– Side Effects: gi distress, weight gain
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Lobert

19. CNS Pharmacology
AntiSeziure Agents
• Hydantoins
– Ex: Phenytoin (Dilantin)
– Action: stabilizes membrane by blocking sodium
channels in repetitive firing neurons
– Therapeutic Effect: first line treatment of epilepsy,
partial and tonic-clonic seizures
– Side Effects: gi irritation, confusion, sedation,
dizziness, headache, ataxia, gingival hyperplasia,
hirsutism
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Lobert

20. CNS Pharmacology
AntiSeziure Agents
• Iminostilbenes
– Ex: Carbamazepine (Tegretol)
– Action: stabilizes membrane by blocking sodium
channels in repetitive firing neurons
– Therapeutic Effect: epilepsy (except absence
seizures), partial and tonic-clonic seizures
– Side Effects: dizziness, drowsiness, ataxia, heart
failure related to ADH release
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Lobert

21. CNS Pharmacology
AntiSeziure Agents
• Second Generation Agents
– Ex: Lamotrigine (Lamictal)
– Ex: Levetiracetam (Keppra)
– Ex: Topiramate (Topamax)
– Ex: Gapapentin (Neurontin)
– Action: variety of mechanisms
– Therapeutic Effect: adjunct treatment of a variety of
seizure disorders
– Side Effects: dizziness, sedation, drowsiness
– Note: many other uses such as for neuropathic pain
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Lobert

22. CNS Pharmacology
Antiparkinsonian Agents
• Levodopa
– Ex: Levodopa/Carbidopa (Sinemet)
– Action: converts to dopamine after crossing blood
brain barrier resolution of dopamine deficiency
– Therapeutic Effect: decreases symptoms of
parkinsons less muscle rigidity, less bradykinesia
– Side Effects: severe nausea and vomiting with
initial administration, cardiac arrhythmias,
postural hypotension; large incidence of
dyskinesias; psychosis, depression, anxiety
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Lobert

23. CNS Pharmacology
Antiparkinsonian Agents
• Treatment Issues
– Diminished response to levodopa
– Fluctuations in response to levodopa
– Drug holidays for levodopa
– Adjunctive symptom reduction with
anticholinergic agents
• Benztropine Mesylate (Cogentin)
• Trihexphenidyl (Artane)
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Lobert

24. CNS Pharmacology
Antiparkinsonian Agents
• Dopamine Agonists
– Ex: Bromocriptine (Parlodel)
– Ex: Pramipexole (Mirapex)
– Ex: Ropinirole (Requip)
– Action: similar function to dopamine
– Therapeutic Effect: treatment of parkinsons
– Side Effects: less adverse effects dyskinesias and
motor response issues are rare; nausea, vomiting,
postural hypotension
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Lobert