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

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 2Lobert

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 3Lobert

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 4Lobert

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 5Lobert

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 6Lobert

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 7Lobert

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 8Lobert

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 9Lobert

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 10Lobert

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 meq/L; lithium is now typically prescribed with antiseizure drugs and other mood stabilizers; consistent sodium dietary intake is necessary 11Lobert

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 12Lobert

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 13Lobert

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 14Lobert

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) 15Lobert

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 16Lobert

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 17Lobert

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 18Lobert

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 19Lobert

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 20Lobert

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 21Lobert

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 22Lobert

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) 23Lobert

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 24Lobert