Drugs Affecting the Central Nervous System PDF

NCMA 216: Pharmacology DRUGS AFFECTING THE BODY SYSTEM & NURSING CONSIDERATIONS CENTRAL NERVOUS SYSTEM Abigael Comson-De Mesa, RN Learning Objectives At the end of the discussion, students will be able to: Review the anatomy and physiology of the Central Nervous 1 System (...

NCMA 216: Pharmacology DRUGS AFFECTING THE BODY SYSTEM & NURSING CONSIDERATIONS CENTRAL NERVOUS SYSTEM Abigael Comson-De Mesa, RN Learning Objectives At the end of the discussion, students will be able to: Review the anatomy and physiology of the Central Nervous 1 System (CNS). 2 Understand the basic concept of the diseases affecting the CNS. 3 Identify classifications of drugs affecting the CNS. 4 Describe the specific actions of the drugs and its adverse effects. Understand the pharmacokinetics of drugs affecting the 5 nervous system. Determine the specific nursing considerations of precautions in 6 safe drug administration. 01 Review of the Anatomy and Physiology of the CNS Central Nervous System ▪ Brain and Spinal Cord (+) vast majority of nerves ▪ Skull – bones protect the brain. ▪ Vertebrae – bones protect the spinal cord. ▪ Meninges – cover the nerves in the brain and spine. Central Nervous System ▪ Blood Brain Barrier ✓ brain defense ✓ keep toxins, proteins, and other structures out of the brain. ✓ facilitates a chemically stable environment. ✓ Lipid-soluble substances – able to cross the blood-brain barrier. Ex: Alcohol, Nicotine, ,and Heroin Water-soluble substances – unable to cross, high ionic charge. Central Nervous System ▪ Circle of Willis ✓ distributes the blood to the brain. ✓ protects the neuron from lack of oxygen and glucose. ✓ (2) Carotid Arteries (both sides of the brain) – front of the head. ✓ (2) Vertebral Arteries – from the back of the head, form the Basilar Arteries. Central Nervous System ▪ Brain ▪ Hindbrain – top of the spinal cord into the midbrain. – brainstem (pons and medulla oblongata) ✓ respiratory center – controls breathing ✓ cardiovascular center – regulate blood pressure ✓ CTZ and emetic center – controls vomiting ✓ swallowing center – coordinates complex swallowing reflex. – cerebellum ✓ coordinates motor function that regulates posture, balance, and voluntary muscle activity. Central Nervous System ▪ Brain ▪ Midbrain – small area above the hindbrain. – cranial nerves ✓ Senses – sight, smell, hearing, balance, taste ✓ Motor – head and neck movement – reticular activating system (RAS) ✓ information transmitter ✓ filters the incoming message – significant only ✓ sleep-wake cycle Central Nervous System ▪ Brain ▪ Forebrain – thalamus ✓ sends direct information into the cerebrum to transfer sensation (cold, heat, pain, touch, muscle sense) – hypothalamus ✓ major sensor for activities in the body. ✓ responsible for temperature control, water balance, appetite, and fluid balance. ✓ central role in endocrine system and autonomic nervous system. Central Nervous System ▪ Brain ▪ Forebrain – limbic system ✓ High levels of (3) neurotransmitters (epinephrine, norepinephrine, serotonin) ✓ Expression of emotions (anger, pleasure, motivation, stress) – (2) cerebral hemispheres ✓ corpus callosum – joined the hemispheres. ✓ sensory neurons – receive nerve impulse. ✓ motor neurons – send nerve impulse. ✓ coordinate speech and communication ✓ learning Central Nervous System ▪ Brain ▪ Basal ganglia – Bottom of the brain. – Make up the extra pyramidal motor system. – Coordinates motor activity – unconscious activities (posture and gait) Central Nervous System ▪ Spinal Cord – 31 pairs of spinal nerves. – 2 components (roots) ▪ Dorsal Root – Spinal Sensory fiber – Brings information into the CNS from the periphery ▪ Ventral Root – Spinal Motor fiber – Carry the information away from CNS to cause movement or reaction.  CENTRAL NERVOUS SYSTEM ***31 pairs of SPINAL NERVES BRAIN SPINAL CORD FOREBRAIN MIDBRAIN HINDBRAIN DORSAL ROOT VENTRAL ROOT SENSORY FIBERS MOTOR FIBERS ❑ Cerebral Cortex ❑ Cranial Nerves ❑ Pons 2 Hemispheres ❑ Medulla Oblongata ❑ Thalamus ❑ Cerebellum ❑ Hypothalamus ❑ Limbic System Sensory Motor Sense of Sight, Head and Neck Hearing, Smell, Movement Taste, and Balance Central Nervous System Controlling the Analyzing Integrating functions of incoming internal and human body. stimuli. external responses. 02 Drugs affecting the CNS  Drugs Affecting the Central Nervous System ANXIOLYTIC ANTI- ANTI- ANTI- ANTI- DRUGS DEPRESSANTS PSYCHOTIC SEIZURE PARKINSON’S ❑ Barbiturates DRUGS DRUGS DRUGS DRUGS ❑ Benzodiazepines ❑ Tricyclic ❑ Typical ❑ Hydantoins ❑ Dopaminergic ❑ Other Anxiolytic Antidepressants Antipsychotic ❑ Barbiturates Drugs and Hypnotic (TCA) Drugs ❑ Benzodiazepines ❑ Anticholinergic Drugs ❑ Mono Amine ❑ Atypical ❑ Succinimides Drugs Oxidase Antipsychotic ❑ Valproate or Inhibitors (MAOI) Drugs Valproic Acid ❑ Selective ❑ Drugs for Bipolar ❑ Other Anti- Serotonin Disorder (Anti- seizure Drugs Reuptake mania) Inhibitors (SSRI) ❑ Drugs for ADHD and Narcolepsy Anxiety CNS Condition Affected by Anxiolytic and Hypnotic Drugs Anxiety ▪ Feeling of tension, nervousness, apprehension, or fear. ▪ Involves unpleasant reactions to stimulus – actual or unknown. ▪ Sympathetic stress reaction. Signs and Symptoms: ✓ Increased heart rate ✓ Rapid breathing ✓ Elevated blood pressure ✓ Sweating Anxiety Levels of Anxiety ▪ Mild Anxiety ✓ Normal body response to a stimulus. ✓ Helps an individual for a wider perspective and focus on certain activities. ▪ Moderate Anxiety ✓ Restlessness and increased sympathetic stress reaction. ✓ Perceptual field narrows. ✓ Need for a drug treatment. ▪ Severe Anxiety ✓ Perceptual field is greatly reduced and focus on particular or scattered details. Anxiety Classification of Anxiety Based on situation, symptoms, and characteristics of the stimuli. ▪ Panic Disorder ✓ Most common form ✓ Markedly disturbed behavior ▪ Generalized Anxiety Disorder ▪ Obsessive-Compulsive Disorder ▪ Social Anxiety Disorder ▪ Post-Traumatic Stress Disorder Anxiolytic Drugs Drugs Affecting Anxiety Disorder Anxiolytic Drugs ▪ Drugs that depress the central nervous system (CNS) ▪ Stops anxiety ▪ Other medications: ✓ Antidepressants – SSRI ❑ First-line treatment for Chronic Generalized Anxiety ✓ Anticonvulsants ✓ Antipsychotics ✓ Antihistamines ✓ Selected drugs act on ANS – controls the sympathetic signs and symptoms Anxiolytics SEDATION ▪ Loss of awareness of and reaction to environmental stimuli. SEDATIVES ✓ Drug that depresses the CNS ✓ Produce loss of awareness of and reaction to environment. ✓ Lead to drowsiness HYPNOSIS ▪ Extreme sedation ▪ Further CNS depression HYPNOTICS ✓ Help people fall asleep ✓ Act on Reticular Activating System (RAS) ✓ Block the brain’s response to incoming stimuli  ▪ Commonly used CNS depressant. ALCOHOL ▪ Enhances the inhibitory neurotransmitter - GABA (Gamma- aminobutyric Acid) ▪ Inhibits the excitatory amino acid – Glutamate ▪ Alcohol Withdrawal Signs and Symptoms: ✓ Nausea and Vomiting ✓ Tonic-Clonic Seizure ✓ Delirium ✓ Tremors ✓ Restlessness ✓ Irritability ✓ Variability in vital signs ✓ Cardiac arrhythmias Treatment: ✓ Benzodiazepines – acute treatment of alcohol withdraw ✓ Antiseizure medications ✓ Naltrexone – suppress alcohol cravings and opioid withdrawal Benzodiazepines ▪ Most frequently used anxiolytic drugs. ▪ Relieve anxiety quickly. ▪ Controlled substance ▪ Recommended for short-term use – potential for dependence Indication: ✓ Anxiety disorders ✓ Alcohol withdrawal ✓ Hyperexcitability and Agitation ✓ Seizure disorders ✓ Insomnia ✓ Preoperative relief of anxiety and tension Mechanism of Action: ✓ Act in the limbic system and RAS – enhance GABA ✓ Interfere with neuron firing, stabilize postsynaptic cell Benzodiazepines Pharmacokinetics: Contraindications: ✓ Absorbed from the gastrointestinal ✓ Allergy tract ✓ Psychosis ✓ Peak levels – 30 mins to 2 hours ✓ Acute narrow-angle glaucoma ✓ Lipid soluble – crosses the placenta, ✓ Shock mammary ✓ Coma ✓ Well-distributed throughout the body ✓ Acute alcoholic intoxication ✓ Metabolize in the liver ✓ Pregnancy – cleft lip or palate, *** Liver Disorders – give small doses inguinal hernia, cardiac – monitor closely defect, microcephaly or ✓ Excretion through the urine pyloric stenosis ✓ Breastfeeding ✓ Opioids – respiratory depression, coma, or death Benzodiazepines Adverse Effects: Drug-to-Drug Interaction: ✓ Nervous system effects ✓ Alcohol and other CNS depressants ✓ Mild paradoxical excitatory reactions Increases risk of CNS depression ✓ Gastrointestinal condition ✓ Cardiovascular problems ✓ Cimetidine ✓ Hematological conditions ✓ Oral contraceptive ✓ Genitourinary effects ✓ Disulfiram ✓ Abrupt cessation Increases effects of benzodiapines ✓ Theophylline Decreases effects of benzodiapines Benzodiazepines DRUG NAME DOSAGE/ ROUTE SPECIAL CONSIDERATIONS Alprazolam 0.25-0.5mg PO t.i.d up to 1-10mg/d PO (Xanax) Reduced dosage in older adults. Clonazepam Adult: 0.25mg PO b.i.d Monitor for suicidal ideation, (Klonopin) Pedia: 0.01-0.03 mg/kg/d PO given 2-3 doses liver function, and blood Do not exceed 0.05mg/kg/d counts with long-term therapy. Diazepam Adult: 2-10mg PO b.i.d to q.i.d. Taper dose after long-term (Valium) 2-2.5mg PO b.i.d. – older adults therapy. 2-10mg IV/ IM Pedia: *varies based on route, indication, and age. Weight-based dosing is common. Lorazepam 2-6mg/d PO in divided doses Monitor injection sites (Ativan) 0.5mg/kg IM and IV to max of 4mg Reduce dosage of narcotics given with this drug Benzodiazepines SPECIAL DRUG NAME DOSAGE/ ROUTE CONSIDERATIONS Midazolam Adult: 5mg IM – sedation Do not administer intra- 1-2.5mg IV – conscious sedation for short arterially procedures Keep resuscitation 10-50mcg/kg IV – sedation in critical care equipment nearby Pedia: 0.1-0.015mg/ kg IM or PO – conscious Be prepared to breathe for sedation for the patient as needed. short procedures 50-100mcg/kg IV – sedation in critical care Benzodiazepines Benzodiazepine Toxicity Treatment: ✓ Flumazenil – benzodiazepine receptor antagonists – reverse sedation and other adverse effects Nursing Considerations: ✓ Do not administer intra-arterially – serious arteriospasm and gangrene ✓ Monitor injection sites – local reactions ✓ Do not mix IV drugs in solution with any other drugs – avoid drug incompatibility ✓ Give IV slowly – prevent hypotension, bradycardia, and cardiac arrest. ✓ Reduce dose of narcotic analgesic – decrease effects and sedation ✓ Be prepared to administer Flumazenil – benzodiazepine toxicity ✓ Maintain patients in bed or advise for precautionary measures, ensure patient safety. ✓ Taper dose gradually after long-term therapy. Barbiturates ▪ Anxiolytic-hypnotics ▪ * No longer considered the mainstay for the treatment of anxiety Indication: Parental form – faster peak levels ✓ Relief of signs and symptoms of anxiety ✓ Acute manic reactions ✓ For sedation ✓ Seizures ✓ For insomnia ✓ Pre-anesthetic ✓ Antiseizure Mechanism of Action: ✓ General CNS depressants ✓ Inhibit neuronal impulse conduction in the ascending RAS ✓ Depress the cerebral cortex ✓ Alter cerebellar function ✓ Depress motor output Barbiturates Pharmacokinetics: Contraindications: ✓ Peak levels – 20 to 60 mins ✓ Allergy ✓ Lipid soluble – crosses the placenta ✓ History of addiction to sedative- and enters human milk hypnotic drugs ✓ Metabolize in the liver ✓ Hepatic impairment *** Liver Disorders – lower doses ✓ Nephritis – monitor closely ✓ Respiratory distress ✓ Excretion through the urine ✓ Severe respiratory dysfunction ✓ Pregnancy ✓ Patients with acute or chronic pain ✓ Seizure disorders Barbiturates Adverse Effects: ✓ CNS depressions ✓ Hypersensitivity reactions ✓ drowsiness ✓ rash ✓ lethargy ✓ Stevens-Johnson syndrome ✓ ataxia ✓ Cardiovascular effects ✓ bradycardia ✓ vertigo ✓ syncope ✓ feeling of a “hangover” ✓ thinking abnormalities IV Administration: ✓ hypotension ✓ paradoxical excitement ✓ hypoventilation ✓ anxiety ✓ respiratory depression ✓ hallucinations ✓ Gastrointestinal effects ✓ laryngospasm ✓ nausea and vomiting ✓ constipation ✓ diarrhea Barbiturates Drug-to-Drug Interaction: ✓ Alcohol, antihistamines, tranquilizers, and other CNS depressants – Increases risk of CNS depression ✓ Phenytoin – Altered response – Evaluate the patient frequently if this combination cannot be avoided ✓ Monoamine oxidase inhibitors – Increased serum levels and effects – Monitor patient closely and adjust doses. ✓ Enzyme Induction Effect – Decreases therapeutic effect ✓ Oral anticoagulant Estrogen ✓ Digoxin Acetaminophen ✓ Tricyclic antidepressants Metronidazole ✓ Corticosteroids Carbamazepine ✓ Oral contraceptives Beta Blockers ✓ Doxycycline Barbiturates DRUG NAME DOSAGE/ ROUTE SPECIAL CONSIDERATIONS Phenobarbital Adult: 30-120mg/d PO IM or IV Taper gradually after long-term Reduced dosage in older adults. use Give IV slowly Pedia: 1-3mg/kg IV or IM Monitor injection sites Barbiturates Nursing Considerations: ✓ Do not administer intra-arterially – serious arteriospasm and gangrene ✓ Monitor injection sites – local reactions ✓ Do not mix IV drugs in solution with any other drugs – avoid drug incompatibility ✓ Give parenteral forms only if oral forms are not feasible or available, switch to oral form as soon as possible – to avoid adverse effects ✓ Give IV slowly – to prevent cardiac problems ✓ Standby life support facilities ✓ Taper dose gradually. ✓ Provide comfort measures. ✓ Patient teaching. ✓ Offer support and encouragement. Other Anxiolytic and Hypnotic Drugs DRUG NAME SPECIAL CONSIDERATIONS Antihistamine ▪ Sedation Diphenhydramine Indications: Promethazine ✓ Preoperative and postoperative medications – decrease use of narcotics ✓ Short-term treatment of insomnia (1 week) ✓ Allergic rhinitis ▪ Drying effects common – monitor patients with thickened respiratory secretions and breathing difficulties Buspirone ▪ Bind to both serotonin and dopamine receptors ▪ NO sedative, anticonvulsant or muscle relaxant properties ▪ Reduces signs and symptoms of anxiety without CNS effects Indication: ✓ Anxiety ▪ Full effect – 1 to 4 weeks Adverse Effects: ✓ Dizziness, Nausea, Headache, Agitation, Constipation, Dry mouth * Small meals – to prevent nausea. Other Anxiolytic and Hypnotic Drugs DRUG NAME SPECIAL CONSIDERATIONS Dexmedetomidine ▪ Alpha 2 adrenergic agonist Precedex ▪ Administered IV Indications: ✓ Sedation – Intubated and Ventilated patients (ICU) ▪ Do not use longer than 24h. ▪ Monitor patients continually. Eszopiclone ▪ React with GABA sites near benzodiazepines receptors Lunesta ▪ Prolonged sleep and decreases awakenings ▪ Adverse effects enhanced if taken with CNS depressants Indication: ✓ Insomnia Nursing considerations: ✓ Take the medication at night ✓ Allow 8 hours sleep Other Anxiolytic and Hypnotic Drugs DRUG NAME SPECIAL CONSIDERATIONS Meprobamate ▪ Acute anxiety ▪ Treatment for up to 4 months ▪ Works in the limbic system and thalamus ▪ Anticonvulsant properties ▪ CNS muscle-relaxing effects Ramelteon ▪ Melatonin receptor agonist ▪ Stimulates melatonin receptors – involved sleep-wake cycle ▪ Treatment of Insomnia – difficulty with sleep onset Side Effects: ✓ Hormonal effects – increase prolactin, decrease testosterone ✓ Worsening sleep apnea ✓ Abnormal thoughts and behaviors ✓ Depression ✓ Impaired mental alertness  Anxiolytic and Hypnotic Drugs Benzodiazepines Barbiturates Other Anxiolytic and Hypnotic Drugs ▪ Alprazolam ▪ Phenobarbital ▪ Antihistamine ▪ Clonazepam ▪ Buspirone ▪ Diazepam ▪ Dexmedetomidine ▪ Lorazepam ▪ Eszopiclone ▪ Midazolam ▪ Meprobamate ▪ Ramelteon Depression CNS Condition Affected by Antidepressant Drugs Depression ▪ Common affective disorder involving feelings of sadness – severe and longer-lasting ▪ Intense moods ▪ Overwhelming feelings of despair, hopelessness, and disorganization. Signs and Symptoms: ✓ little energy ✓ sleep disturbances ✓ altered appetite ✓ altered libido ✓ reduced ability to do activities of daily living Depression Types of Depression Based on DSM-5 Multiple Depressive Disorders Specific criteria for the diagnosis of each type of disorder ▪ Major Depressive Disorder ▪ Persistent Depressive Disorder ▪ Premenstrual Dysphoric Disorder (PMDD) ▪ Disruptive Mood Dysregulation Disorder Depression Biogenic Theory of Depression ▪ Deficiency of the biogenic amines in the key areas of the brain. ▪ Biogenic Amines: ▪ Norepinephrine ▪ Dopamine ▪ Serotonin Depression Nerve Impulse Limbic System: PRE-SYNAPTIC ✓ Norepinephrine (NE) ✓ Serotonin (5HT) ✓ Dopamine Firing of Neurotransmitters To Regulate arousal, alertness, (Synapse) attention, moods, appetite, and sensory processing. POST-SYNAPTIC Binds with the Neurotransmitters Receptors Neurotransmitters are removed by an go back to the pre- enzyme synaptic neuron MONO AMINE REUPTAKE OXIDASE Antidepressant Drugs Drugs Affecting Depression Antidepressants ▪ Alter the concentration of neurotransmitters in the brain – most effective treatment for depression 3 Counteract Ways: ✓ Inhibit the effects of monoamine oxidase (MAO) ⇧neurotransmitters levels from the neuron synaptic cleft ✓ Block the reuptake of the neurotransmitters by the releasing nerve. ⇧neurotransmitters levels in the synaptic cleft ✓Regulate receptor sites and the breakdown of neurotransmitters. Accumulation of neurotransmitters in the synaptic cleft Tricyclic Antidepressants (TCA) ▪ Reduces the reuptake of norepinephrine and the serotonin ▪ Anticholinergic Indication: ✓ Relief of signs and symptoms of depression ✓ Anxiety ✓ Sleep disturbances ✓ Enuresis (bed wetting) – kids older than 6 years old ✓ Chronic and intractable pain – neuropathy and fibromyalgia Mechanism of Action: ✓ Inhibit presynaptic reuptake – Norepinephrine (NE) and Serotonin (5HT) ✓ Accumulation of neurotransmitters in the synaptic cleft ✓ Increase stimulation of post-synaptic receptors. ✓ ⇧ NE and 5HT levels Tricyclic Antidepressants (TCA) Pharmacokinetics: Cautions: ✓ Absorbed in GIT ✓ Preexisting cardiovascular ✓ Peak levels: 2 to 4 hrs disorders ✓ Lipid soluble ✓ Conditions exacerbated by ✓ Metabolized in the liver anticholinergic effects ✓ Excreted in the urine ✓ Psychosis ✓ Cross the placenta and human milk ✓ Paranoia ✓ Manic-depression Contraindications: ✓ History of seizures ✓ Allergy – hypersensitivity reactions ✓ Hepatic failure ✓ Myocardial Infarction – potential ✓ Renal dysfunction reinfarction ✓ Myelography procedure – drug-to-drug interaction in the dye ✓ MAOI – serious adverse effects and toxic reactions ✓ Pregnancy ✓ Lactation Tricyclic Antidepressants (TCA) Adverse Effects: ✓ CNS ✓ GUT ✓ Sedation ✓ Urinary retention ✓ Sleep disturbances ✓ Loss of libido ✓ Hallucinations ✓ Changes in sexual functioning ✓ Disorientation ✓ CVS ✓ Difficulty concentrating Orthostatic hypotension ✓ ✓ Weakness ✓ Hypertension ✓ Tremors ✓ Tachycardia ✓ GIT ✓ Arrhythmias ✓ Dry mouth ✓ Myocardial Infarction ✓ Constipation ✓ Anticholinergic ✓ Nausea and Vomiting ✓ Blurred vision ✓ Decreased salivation ✓ Photophobia ✓ Anorexia Tricyclic Antidepressants (TCA) Drug-to-drug interactions: ✓ Cimetidine, Fluoxetine, Ranitidine ▪ Increases therapeutic and adverse effects ▪ Close patient monitoring ▪ Appropriate dose reductions ✓ Oral Anticoagulants ▪ High serum levels of anticoagulants ▪ Increase risk of bleeding ▪ Frequent blood tests ✓ Sympathomimetic Drugs (Clonidine) ▪ Increase risk of arrhythmia and hypertension ✓ MAOI ▪ Risk for severe serotonin syndrome ▪ Risk for hyperpyretic symptoms – convulsions, hypertension, death Tricyclic Antidepressants (TCA) Nursing Considerations: DRUG NAME ✓ Warn patient and family members about risk of worsening depression and suicidal thoughts. Amitriptyline ✓ Maintain initial dose for 4 to 8 weeks to evaluate the Amoxapine therapeutic effect. Clomipramine ✓Administer parenteral forms of the drug only if oral forms Imipramine are not feasible or available. ✓ Administer the dose at bedtime if drowsiness and anticholinergic effects are severe. Avoid hazardous activities. ✓ Reduce dose if minor adverse effects occur. Discontinue if major or potentially life-threatening adverse effects. ✓ Provide comfort measures. ✓ Provide thorough patient teaching. ✓ Offer support and encouragement. Monoamine Oxidase Inhibitors (MAOI) ▪ Inhibit MAO – enzyme that breaksdown the biogenic amines norepinephrine, dopamine, and serotonin. Indication: ✓ Treatment of the signs and symptoms of depression in patients who cannot tolerate or do not respond to other safer antidepressants. Mechanism of Action: ✓ Blocking the breakdown of biogenic amines – NE, Dopamine and 5HT. ✓ Increases stimulation of the postsynaptic receptors. ✓ Relief of depression Monoamine Oxidase Inhibitors (MAOI) Pharmacokinetics: Contraindications: ✓ Absorbed in GIT ✓ Allergy – hypersensitivity reactions ✓ Peak levels: 2 to 3 hrs ✓ Pheochromocytoma – tumor in the adrenal ✓ Metabolized in the liver glands ✓ Excreted in the urine (Increase NE levels – severe HPN) ✓ Cross the placenta and human ✓ Hypertension milk ✓ Coronary Artery Diseases – Angina ✓ Congestive Heart Failure ✓ CNS vessels abnormalities ✓ Hepatic Failure ✓ Renal Impairment ✓ Bipolar Disorder – overstimulated ✓ Seizure Disorder ✓ Patients who will undergo elective surgery ✓ Pregnant ✓ Lactating mothers Monoamine Oxidase Inhibitors (MAOI) ***accumulatio of norepinephrine in the ✓ GUT synaptic cleft ✓ Urinary retention Adverse Effects: ✓ Dysuria ✓ Dizziness ✓ Incontinence ✓ Excitement ✓ Changes in sexual functioning ✓ Nervousness ✓ CVS ✓ Mania ✓ Orthostatic hypotension ✓ Hyperflexia and Tremors ✓ Arrhythmias ✓ GIT ✓ Palpitations ✓ Dry mouth ✓ Hypertensive Crisis ✓ Diarrhea or Constipation Signs and Symptoms: ✓ Abdominal pain - Occipital Headache ✓ Nausea and Vomiting - Neck stiffness ✓ Weight gain - Nausea and Vomiting ✓ Anorexia Monoamine Oxidase Inhibitors (MAOI) Drug-to-drug interactions: ✓ Other antidepressants ▪ Increases risk of hypertensive crisis ▪ Coma ▪ Severe convulsions with TCAs ✓ SSRI ▪ Life-threatening serotonin syndrome ▪ 6 weeks – before starting MAOI therapy ✓ Sympathomimetic Drugs – Methyldopa ▪ Increases sympathomimetic effect ✓ Insulin (Oral Antidiabetics) ▪ Additive hypoglycemic effects Monoamine Oxidase Inhibitors (MAOI) Drug-to-food interactions: TYRAMINE CONTAINING ✓ Tyramine FOODS ▪ Breakdown of tyrosine ▪ Normally broken down by MAO Cheddar cheese Beef liver/ Chicken pate enzymes in the GI tract Fermented meats ▪ Absorbed in high concentrations Corned beef in the presence of MAOIs – Sausage, Pepperoni, Salami resulting in increased blood Avocados pressure Beer ▪ Causes release of stored NE from Distilled liquors – vodka, gin nerve terminals – contributes to Chocolate Fruits – figs, raisins, grapes, high blood pressure and pineapple, oranges hypertensive crisis. Sour cream Yogurt Monoamine Oxidase Inhibitors (MAOI) Nursing Considerations: DRUG NAME ✓ Limit drug access to potentially suicidal patient to Isocarboxazid decrease the risk of self-harm. ✓ Monitor the patient for 2-12 weeks to ascertain the onset Phenelzine of the full therapeutic effect. Tranylcypromine ✓ Monitor blood pressure and orthostatic blood pressure carefully to arrange for a slower increase in dose. ✓ Discontinue drug and monitor the patient carefully – severe headache to decrease the risk of severe hypertension and cerebrovascular effects. ✓ Phentolamine – standby treatment for Hypertensive Crisis. ✓ Provide comfort measures. ✓ Avoid tyramine containing foods. ✓ Provide thorough patient teaching. ✓ Offer support and encouragement to help patient cope. Selective Serotonin Reuptake Inhibitors (SSRI) ▪ Block the reuptake of 5HT with little to no known effect on norepinephrine. ▪ Better choice for many patients – prescribed first before TCA and MAOI. ▪ First-line therapy for both depression and anxiety disorders Indication: ✓ Treatment of the signs and symptoms of depression in patients who cannot tolerate or do not respond to other safer antidepressants. Mechanism of Action: ✓ Blocking the breakdown of biogenic amines – NE, Dopamine and 5HT. ✓ Increases stimulation of the postsynaptic receptors. ✓ Relief of depression Selective Serotonin Reuptake Inhibitors (SSRI) Pharmacokinetics: Contraindications: ✓ Absorbed in GIT ✓ Allergy – hypersensitivity reactions ✓ Peak levels: 2 to 3 hrs ✓ Hepatic Failure ✓ Excreted in the urine and feces ✓ Renal Impairment ✓ Diabetes – exacerbated by the stimulating effects of these drugs. ✓ Severely depressed or suicidal patients ✓ Pregnant – pulmonary and cardiac problems in the newborn ✓ Lactating mothers – adverse effects in the baby Selective Serotonin Reuptake Inhibitors (SSRI) Adverse Effects: ✓ Respiratory Effects ✓ CNS Effects ✓ Dyspnea ✓ Headache ✓ Cough ✓ Drowsiness ✓ Upper Respiratory Infection ✓ Dizziness ✓ Pharyngitis ✓ Insomnia ✓ Serious Intraocular Pressure Changes ✓ Anxiety ✓ Sweating ✓ Agitation ✓ Rash ✓ GI Effects ✓ Fever ✓ Nausea and Vomiting ✓ Pruritus ✓ Diarrhea or Constipation ✓ Suicidal Ideation ✓ Anorexia ✓ Serotonin Syndrome ✓ Dry Mouth ✓ Confusion, Agitation, Disorientation, Hallucination ✓ GU Effects ✓ Seizure, Tachycardia, Labile blood pressure ✓ Painful menstruation ✓ Fever, Hyperreflexia, Tremors, ✓ Cystitis ✓ Abdominal pain ✓ Coma ✓ Sexual Dysfunction Selective Serotonin Reuptake Inhibitors (SSRI) Drug-to-drug interactions: ✓ MAOI ▪ Increase risk of serotonin syndrome ✓ TCA ▪ Increase therapeutic and toxic effects ✓ Substances that increases 5HT (SNRIs, St. John’s wort, Triptans, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone, Ampethamines) ▪ Increase risk of serotonin syndrome ✓ Aspirin, NSAIDs, Antiplatelet Drugs ▪ Increase risk of bleeding Selective Serotonin Reuptake Inhibitors (SSRI) Nursing Considerations: DRUG NAME ✓ Administer the drug in morning, divide doses if GI upset Fluoxetine occurs. ✓ Provide comfort, safety measures Paroxetine ✓ Small meals Sertraline ✓ Void before dosing Citalopram ✓ Side rails – to prevent fall and protect from dizziness Escitalopram ✓ Limit dosage – to prevent suicidal attempt. ✓ Lower dose – hepatic impairment ✓ Provide support and reassurance ✓ Provide patient teaching Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) ▪ Decrease neuronal uptake of both serotonin and norepinephrine. ▪ More weakly inhibit dopamine. ▪ Do not inhibit MAO. Indication: ✓ Treatment of Major Depressive Disorder Mechanism of Action: ✓ Increasing the levels of both serotonin and norepinephrine in the synaptic cleft. Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) Pharmacokinetics: Contraindications: ✓ Absorbed in GIT ✓ Allergy – hypersensitivity reactions ✓ Metabolized in the liver ✓ Hepatic Failure ✓ Excreted in the urine ✓ Renal Impairment ✓ MAOI ✓ Severely depressed or suicidal patients ✓ Bipolar disorder ✓ Patients risk of seizure ✓ Pregnant – pulmonary and cardiac problems in the newborn ✓ Lactating mothers – adverse effects in the baby Serotonin Norepinephrine Reuptake Inhibitors (SNRI) Side Effects: Adverse Effects: ✓ Nausea and Vomiting ✓ Serotonin syndrome ✓ Constipation ✓ Hypertension ✓ Dizziness ✓ Abnormal bleeding ✓ Headache ✓ Angle closure glaucoma ✓ Increased heart rate ✓ Urinary retention ✓ Hyperhidrosis ✓ Erectile Dysfunction ✓ Decreased libido ✓ Tachycardia ✓ Palpitations Serotonin Norepinephrine Reuptake Inhibitors (SNRI) Drug-to-drug interactions: ✓ MAOI ▪ Increase risk of serotonin syndrome ✓ TCA or SSRI ▪ Increase risk of side effects ✓ Serotonergic substances (Tricyclic, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone, Amphetamines, and St. John’s wort) ▪ Increase risk of serotonin syndrome ✓ Aspirin, NSAIDs Antiplatelet drug, Drugs affecting Coagulation ▪ Increase risk of bleeding Serotonin Norepinephrine Reuptake Inhibitors (SNRI) DRUG NAME Nursing Considerations: ✓ Consider lower dose in older adult patients and Duloxetine patients with hepatic impairment. Levomilnacipran ✓ Monitor patients for up to 4 weeks – full therapeutic effects. Veniafaxine ✓ Establish suicide precautions – severely depressed Desveniafexine patients. Milnacipran – fibromyalgia ✓ Administer drug once a day in the morning – optimal therapeutic effect. ✓ Discuss potential decreased sexual function and strategies for coping. ✓ Provide comfort measures. ✓ Provide patient teaching. ✓ Offer support and encouragement. Other Antidepressants ▪ Effective in treating depression in patients who do not respond to other antidepressants. DRUG NAME SPECIAL CONSIDERATIONS Bupropion ▪ Weakly blocks reuptake of NE and 5HT ▪ Effective for smoking cessation ▪ Available in sustained release formulation ▪ More convenient Mirtazapine ▪ Ability to antagonize alpha 2 receptors – increases NE and 5HT ▪ Antagonize histamine receptors – drowsiness effect Indication: ✓ Major Depression - adult Adverse Effects: ✓ Orthostatic Hypotension Other Antidepressants ▪ Effective in treating depression in patients who do not respond to other antidepressants. DRUG NAME SPECIAL CONSIDERATIONS Nefazodone ▪ Short half-life ▪ Associated with liver toxicity Trazodone ▪ Blocks 5HT ▪ Effective in some forms of depression but has many adverse effects.  Antidepressant Drugs TCA MAOI SSRI SNRI ▪ Amitriptyline ▪ Isocarboxazid ▪ Amitriptyline ▪ Duloxetine ▪ Amoxapine ▪ Phenelzine ▪ Amoxapine ▪ Levomilnacipran ▪ Clomipramine ▪ Clomipramine ▪ Veniafaxine ▪ Tranylcypromine ▪ Desveniafaxine ▪ Imipramine ▪ Imipramine ▪ Milnacipran Other Antidepressants ▪ Bupropion ▪ Mirtazapine ▪ Nefazodone ▪ Trazodone Mental Disorders CNS Condition Affected by Psychotherapeutic Drugs Mental Disorders ▪ Inherent dysfunction within the brain ▪ Abnormal thought processes and responses. ▪ Chemical imbalance in the specific areas of the neurological system. SCHIZOPHRENIA ▪ Most common type of psychosis. ▪ Positive Symptoms ▪ Dysregulation of Dopamine and ▪ Hallucinations Serotonin ▪ Paranoia ▪ Deficient GABA ▪ Delusions ▪ Disorganized Speech ▪ Disorganized Behavior ▪ Negative Symptoms ▪ Apathy ▪ Lack of Emotional Expression ▪ Anhedonia ▪ Mismatched Affect Mental Disorders BIPOLAR ▪ Extremes of depression alternating with hyperactivity, euphoria, and excitement. ▪ Bipolar I ✓ One or more manic episodes alternating with major depression episodes. ▪ Bipolar II ✓ Major depressive episode alternated with at least one hypomanic or less severe manic episode. ▪ Cyclothymia ✓ Similar to Bipolar I, less severe symptoms ▪ Rapid Cycling Type ✓ Four or more manic episodes ✓ Biochemical imbalance, overcompensation on the part of the neurons Mental Disorders NARCOLEPSY ▪ Daytime sleepiness and sudden periods of loss of wakefulness. ▪ Disorder reflect problems with rapid eye movement (REM) sleep regulation. ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD) ▪ Persistent behavior demonstrating inattention, hyperactivity, impulsivity emerge during childhood. ▪ Alterations in the dopaminergic, serotonergic, and glutamatergic neurotransmitter. ▪ Inflammatory component – reduction in cortical gray matter volume in specific areas of the brain. Antipsychotic Drugs Drugs Affecting Mental Disorders Antipsychotic ▪ Dopamine receptor blockers ▪ Treat disorders involve thought processes – organize their thoughts and respond appropriately to stimuli. ▪ Neuroleptic Drugs – neurological adverse effects ▪ Major Tranquilizers ▪ Change in neuron stimulation and response. Typical Antipsychotic Drugs ▪ Block dopamine receptors ▪ Anticholinergic effects ▪ Antihistamine effects ▪ Alpha adrenergic blocking effects ▪ Prevent stimulation of the post-synaptic neurons by dopamine ▪ Depress the reticular activating system (RAS) – limiting the stimuli coming into brain. Atypical Antipsychotic ▪Drugs Block both the dopamine and serotonin receptors ▪ Help alleviate unpleasant neurological effects and depression Typical Antipsychosis Drugs DRUG NAME SPECIAL CONSIDERATIONS Chlorpromazine ▪ Older antipsychotics. ▪ Used to decrease preoperative restlessness and apprehension. ▪ Adjunct treatment of tetanus. ▪ To control nausea and vomiting, and intractable hiccups. Haloperidol ▪ Treat acute psychiatric situations ▪ Intravenous (IV) – prolonged parenteral therapy Prochlorperazine ▪ To control severe nausea and vomiting associated with surgery and chemotherapy. ▪ Oral, Rectal, and Parenteral Forms Atypical Antipsychosis Drugs DRUG NAME SPECIAL CONSIDERATIONS Aripiprazole ▪ Treatment for schizophrenia, major depressive disorder, bipolar disorders, irritability associated with autism spectrum disorder ▪ Parenteral form – agitation with schizophrenia or bipolar mania Lurasidone ▪ Treatment for schizophrenia in adults Lumateperone Olanzapine ▪ Treatment for bipolar disorders Ziprasidone ▪ Parenteral form – acute agitation Quetiapine ▪ Short-term treatment for acute manic episodes associated with bipolar disorders Risperidone ▪ Treatment for irritability and aggression – Autism in children and adolescents ▪ Acute manic episodes and bipolar disorders. Atypical Antipsychosis Drugs DRUG NAME SPECIAL CONSIDERATIONS Paliperidone ▪ Treatment for schizoaffective disorder. Brexpiprazole ▪ Treatment for schizophrenia. ▪ Adjunctive therapy with antidepressants – major depressive disorder Cariprazine ▪ Treatment for schizophrenia – adults ▪ Acute treatment – bipolar I disorder Antipsychotic Drugs Pharmacokinetics: ✓ Absorbed in GIT (depends on the preparation of the drug) * IM administration - 4x active dose than PO * Caution when switching between routes of administration. ✓ Widely distributed in tissues * Stored and released – 6 months after the drug is stopped. ✓ Metabolized in the liver * Children metabolize faster than adults * Older adults metabolize more slower. * Clinical effects not seen for several weeks, advise to continue taking the drugs. ✓ Excreted in the urine Antipsychotic Drugs Contraindications: ▪ Diseases that could exacerbated by dopaminergic blocking effects ✓ Parkinson’s Disease * Prolong QTc Interval * Increase risk of Torsade de Point ✓ Dementia * Increase risk of cardiovascular disease * Death ▪ Diseases that could exacerbated by anticholinergic effects ✓ Glaucoma ✓ Peptic Ulcer ✓ Urinary or Intestinal Obstruction ▪ Seizure disorders ▪ Active alcohol use disorders * CNS Depression Antipsychotic Drugs Contraindications: ▪ Pregnancy ✓ 3RD Trimester * Extrapyramidal effects * Withdrawal symptoms ▪ Children younger than 12 years old with CNS infection and chicken pox * Dystonia ▪ Immunosuppressed and cancer patients * Bone marrow suppression * Blood dyscrasia Antipsychotic Drugs Adverse Effects: ▪ CNS Effects ✓ Sedation ✓ Weakness ✓ Tremor ✓ Drowsiness ✓ Extrapyramidal Side Effects o Pseudoparkinsonism – muscle tremors, rigidity, shuffling gait o Dystonia – spasms of tongue, neck, back, and legs o Akathisia – continuous restlessness o Tardive Dyskinesia – lip smacking, sticking out of the tongue Treatment: * Deutetrabenazine * Valbenazine Antipsychotic Drugs Adverse Effects: ▪ CNS Effects ✓ Neuroleptic Malignant Syndrome o High grade fever o Blood pressure fluctuations o Dysrhythmia – extreme tachycardia o Muscle Rigidity Treatment: * Stop the medication that triggered the syndrome. * Cooling the patient – ice packs, cool fluids, antipyretic drugs * Dantrolene – decrease muscle rigidity * Antiarrhythmic drugs – dysrhythmia ▪ Anticholinergic Effects ▪ Cardiovascular Effects * Baseline ECG during therapy Antipsychotic Drugs Adverse Effects: ▪ Diabetes Mellitus and Weight Gain ▪ Fatal skin reactions and Drug Reaction with Eosinophilia and System Symptoms Ziprasidone * Increase levels of eosinophils – immune response ▪ Respiratory Effects ✓ Laryngospasm ✓ Dyspnea ✓ Bronchospasm ▪ Bone Marrow Suppression ▪ Urine discoloration ✓ Pink to Reddish Brown Urine Color ✓ NO CLINICAL SIGNIFICANCE Phenothiazines – Chlorpromazine, Fluophenazine, Promethazine Antipsychotic Drugs Drug-to-Drug Interactions: ▪ Antipsychotic – Alcohol * Increase CNS depression ▪ Antipsychotic – Anticholinergic * Increase anticholinergic effects ▪ Thioridazine or Ziprasidone * Prolongation of QTc interval – arrhythmia Antipsychotic Drugs Nursing Considerations: ✓ Do not allow the patient to crush or chew sustained-release capsules. * Avoid speeding the absorption * Prevent toxicity ✓ Parental administration – keep the patient in recumbent position 30 mins. * Reduce orthostatic hypotension ✓ Warning the patient about adverse effects: * Tardive Dyskinesia * Extrapyramidal Syndrome ✓ Teach comfort strategies for coping. ✓ Monitor CBC to arrange to discontinue the drug at signs of Bone Marrow Suppression. ✓ Monitor blood glucose levels – long-term therapy ✓ Arrange for gradual dose reduction after long-term use. * Prevent withdrawal symptoms ✓ Provide positioning of legs and arms. * Decrease discomfort of dyskinesia Antipsychotic Drugs Nursing Considerations: ✓ Offer sugarless candy and ice chips * Increase secretions ✓ Give frequent mouth care * Prevent dry mouth ✓ Ensure safety measures – side rails and assistance in ambulation * Prevent falls and other injuries ✓ Patient teaching: * Urine discoloration * Therapeutic effect will take several weeks * Adverse effects Mania ▪ State of hyperexcitability at the opposite pole from depression. ▪ Bipolar disorder ▪ Instability of certain neurons in the brain. Anti-manic Drugs ▪ Treat manic episodes. ▪ Atypical antipsychotic drugs ▪ Antiepileptic agents DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts ▪ Traditional treatment of mania. (Lithobid) ▪ Administer PO – management of manic episodes and prevention of future manic episodes. ▪ Therapeutic Serum Levels: 0.6 to 1.2 mEq/ L  DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts Therapeutic actions: (Lithobid) ▪ Alters sodium transport in nerve and muscle cells. ▪ Inhibits the release of norepinephrine and dopamine. ▪ Selectively modulate the responsiveness of hyperactivity. Pharmacokinetics: ▪ Absorbed GI tract ▪ Peak levels: 30mins to 3 hrs ▪ Same distribution pattern in the body as water ▪ Excreted from the kidney – 80% reabsorbed * Sodium depletion/ dehydration – kidney reabsorbs more lithium into the serum. * Toxicity Contraindication: ▪ Hypersensitivity ▪ Renal or Cardiac diseases ▪ Metabolic disorders  DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts Contraindication: (Lithobid) ▪ Patients using diuretics – severe hyponatremia ▪ Pregnancy * Advise to use birth control pills while on therapy ▪ Lactation Caution: ▪ Protracted diarrhea – 4x or more passage of watery stools/ day ▪ Excessive sweating * alter sodium levels ▪ Suicidal or impulsive patients ▪ Infection with fever * toxic effects Adverse effects: ▪ Weight gain ▪ Renal toxicity ▪ Goiter – irregular growth of thyroid gland ▪ Hypothyroidism  DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts ❑ Serum levels – less than 1.5 mEq/L (Lithobid) CNS problems related to renal toxicity, beginning of gastric toxicity ❑ Serum levels – 1.5 to 2 mEq/L Intensification of all foregoing reactions Brugada’s syndrome ❑ Serum levels – 2 to 2.5 mEq/L Progression of CNS effects and cardiovascular effects Large output of dilute urine – renal toxicity Fatalities – pulmonary toxicity ❑ Serum levels – greater than 2.5 mEq/L Complex multiorgan toxicity Death Drug-to-Drug Interactions: ▪ Lithium – Haloperidol * Encephalopathic syndrome  DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts Drug-to-Drug Interactions: (Lithobid) ▪ Neuromuscular Blocking Agents * Prolonged effects ▪ Serotonergic Drugs * Trigger Serotonin Syndrome ▪ Lithium – Herbal Substance: Psyllium * Blocks absorption of lithium ▪ Lithium – Carbamazepine * Increases CNS toxicity ▪ Lithium – Iodide Salt * Increases risk of hypothyroidism ▪ Lithium – Thiazide Diuretics * Increases lithium toxicity * Decreases sodium levels and increases lithium retention ▪ Lithium – Urine Alkalinizing Drugs: Antacids and Tromethamine * Decreases effectiveness of lithium ▪ Lithium - Indomethacin and NSAIDs * Increases plasma levels of lithium  DRUG NAME SPECIAL CONSIDERATIONS Lithium Salts Nursing Considerations: (Lithobid) ✓ Administer drug cautiously – frequent monitoring of serum lithium levels. ✓ Administer drug with food or milk – to alleviate GI upset ✓ Arrange decrease dose after treatment of acute manic episode ✓ Ensure adequate intake of salt and fluids * Dehydration ✓ Monitor clinical status * Hemodialysis ✓ Arrange small, frequent meals, give sugarless lozenges, offer mouth care ✓ Provide safety measures ✓ Patient teaching ✓ Offer support and encouragement CNS Stimulants ▪ Treatment for ADHD and Narcolepsy ▪ Calm hyperactive children ▪ Help focus on one activity in longer periods ▪ Redirect and excite the arousal stimuli from the RAS Indication: ✓ ADHD ✓ Narcolepsy ✓ Improvement of wakefulness – sleep disorders Mechanism of Action: ✓ Increasing the release of catecholamines from presynaptic neurons. * Blockage of norepinephrine and dopamine reuptake ✓ Increasing the stimulation of postsynaptic neurons. CNS Stimulants DRUG NAME SPECIAL CONSIDERATIONS Methamphetamine HCl ▪ Treatment of ADHD Methylphenidate Dexmethylphenidate ▪ Lower doses than methylphenidate Dextroamphetamine ▪ Treatment of narcolepsy Lisdexamfetamine ▪ Treatment of ADHD ▪ Treatment of binge-eating disorders Armodafinil ▪ Dopaminergic mechanism ▪ Not associated with cardiac and systemic stimulatory effects ▪ Management for Obstructive Sleep Disorders – Sleep Apnea CNS Stimulants DRUG NAME SPECIAL CONSIDERATIONS Atomoxetine ▪ Selective Norepinephrine Reuptake Inhibitor ▪ Anticholinergic effects ▪ No cardiovascular and stimulatory effects ▪ Preferable treatment ADHD Alpha 2 Adrenergic Agonists Clonidine ▪ Treatment for ADHD Guanfacine ▪ Treatment for ADHD in extended-release tab form ▪ Attention and impulsivity  Antipsychotic Drugs Typical Atypical Anti-mania CNS Antipsychotic Antipsychotic Drugs Stimulants Drugs Drugs ▪ Lithium Salts ▪ Amphetamine ▪ Haloperidol ▪ Aripiprazole ▪ Armodafinil ▪ Chlorpromazine ▪ Cariprazine ▪ Atomoxetine ▪ Prochlorperazine ▪ Lurasidone ▪ Clonidine Quetiapine ▪ Dexmethylphenidate ▪ Fluphenazine ▪ ▪ Dextroamphetamine ▪ Olanzapine ▪ Guanfacine ▪ Ziprasidone ▪ Methamphetamine ▪ Risperidone ▪ Methylphenidate ▪ Paliperidone Seizure Disorders CNS Condition Affected by Antiseizure Drugs Seizure ▪ Sudden abnormal discharge of excessive electrical energy from neurons in the brain. ▪ Associated with signs and symptoms based on the affected area of the brain. ▪ Tonic-clonic muscle contractions ✓ Tonic – Stiffening ✓ Clonic – Jerking ▪ Sympathetic reactions ▪ Electroencephalogram (EEG) – examines brain wave patterns. Seizure ▪ Theories of Seizure Etiology: ❑ Impairment of the cell membrane of certain neurons that changes membrane permeability or distribution of ions. ❑ Structural differences in the cortical or thalamic nerves that result in decreased inhibition. ❑ Higher amounts of neurotransmitter acetylcholine ❑ Deficiency of GABA ❑ Genetic mutations – Ion channel defects ❑ Abnormal neurons – sensitive to stimulation (overrespond) Seizure Classification of Seizures Primary Seizures ▪ International League Against Epilepsy 2017 ▪ Caused by abnormal cells ▪ No underlying cause ▪ Epilepsy Secondary Seizures ▪ Caused by neurological disease/ injury: ▪ Head injury ▪ Drug overdose ▪ Electrolyte alterations ▪ Environmental exposure Generalized Seizure TYPE CHARACTERISTICS Tonic-Clonic Seizure ▪ Motor type of seizure ▪ Grand mal seizure ▪ Incontinence of bladder and bowel ▪ Unconsciousness, confusion, and lethargy – Postictal Phase (Recovery) Absence Seizure ▪ Nonmotor generalized seizure ▪ Abrupt and brief loss of consciousness (3 to 5 sec) ▪ Common in children: 3 years old ▪ Do not involve with muscle contractions ▪ Blank stare, Motionless, Unresponsive ▪ EEG – diagnostic test Myoclonic Seizure ▪ Either motor or nonmotor ▪ Short, sporadic periods of muscle contractions – face, trunk, or one or bilateral extremity ▪ Cerebral stimuli ▪ Rare ▪ Secondary seizure Generalized Seizure TYPE CHARACTERISTICS Febrile Seizure ▪ Very high fever ▪ Tonic-clonic seizure ▪ Common in children: 3 months to 6 years old ▪ DO NOT REQUIRE DAILY ANTISEIZURE DRUG ▪ Self-limiting ▪ Do not appear once temperature decrease. Atonic Seizure ▪ Generalized or Focal ▪ Sudden loss of muscle tone – Limp extremities and facial muscles ▪ Drop attacks Status Epilepticus ▪ Medical emergency ▪ Seizure rapidly recur without cognitive recovery in between. ▪ Most severe form of generalized seizure. Focal Seizure ▪ Partial Seizure ▪ Involve one area of the brain – originate from one site and do not spread throughout the entire organ. ▪ Signs and symptoms – depend on the area ▪ Classification: ▪ Retain awareness ▪ Impaired awareness ▪ Motor ▪ Nonmotor Antiseizure Drugs Drugs Affecting Seizure Disorders Antiseizure Drugs ▪ Treat generalized seizures stabilize the nerve membranes by blocking channels in the cell membrane or alternating receptor sites. ▪ Sedation ▪ CNS depression Generalized Seizure ▪ Drugs affect the entire brain ▪ Reduce the chance of sudden electrical outburst Classification of Antiseizure Drugs ▪ Hydantoins ▪ Barbiturates ▪ Benzodiazepines ▪ Succinimides Antiseizure Drugs Generalized Seizure ▪ Absence Seizure ▪ Succinimides ▪ Drugs modulate the inhibitory neurotransmitter - GABA Antiseizure Drugs GENERALIZED SEIZURE DRUG SPECIAL CONSIDERATIONS HYDANTOINS ▪ Older medication ▪ Phenytoin ▪ Less sedating and less dependency forming ▪ Fosphenytoin Mechanism of Action: ▪ Stabilize nerve membranes throughout CNS directly influencing ionic channels in the cell membrane ▪ Decreasing excitability and hyperexcitability to stimulation ▪ Reduce tonic-clonic, muscular, and emotional responses to stimulation. Therapeutic Serum Levels: Phenytoin – 10 to 20 mcg/ ml Route of Administration: Fosphenytoin – IM/ IV Phenytoin – PO/ Parenteral Antiseizure Drugs GENERALIZED SEIZURE DRUG SPECIAL CONSIDERATIONS HYDANTOINS ▪ Do not discontinue the drug on pregnant patients – status epilepticus ▪ Phenytoin ▪ Patients on Fosphenytoin IV – require careful monitoring for ▪ Fosphenytoin cardiovascular status during infusion period. BARBITURATES ▪ Inhibit impulse conduction ▪ Phenobarbital ▪ Depress cerebral cortex, alter cerebral function, and depress motor nerve output. ▪ Long-term treatment of generalized tonic-clonic seizure ▪ Emergency cases – Acute convulsive episodes and Status epilepticus ▪ PO/ Parenteral forms ▪ Very low lipid solubility – slow onset and very long duration ▪ Therapeutic Serum Levels: 10 to 40 mcg/ ml Drug-to-drug Interaction: ▪ Vitamin K and D – decrease synthesis ▪ Warfarin – decrease effectiveness Antiseizure Drugs GENERALIZED SEIZURE DRUG SPECIAL CONSIDERATIONS BENZODIAZIPINES ▪ Potentiate effects of GABA, stabilizes nerve cell membrane. ▪ Diazepam ▪ Act on limbic system and RAS – muscle relaxation and relieve anxiety ▪ Clonazepam ▪ Limited toxicity and tolerated by patients Route of Administration: Diazepam – PO/ Rectal Clonazepam – Oral disintegrating tablet *Good for patients difficulty swallowing capsules and tablets SUCCINIMIDES ▪ Treatment for Absence seizure ▪ Ethosuximide ▪ Suppress abnormal electrical activity in the brain – inhibitory pathways ▪ Methsuximide in the brain. ▪ Ethosuximide – first tried ▪ Methsuximide – reserved, more adverse effects Drug-to-drug Interactions: ▪ Primidone – first generation barbiturate Antiseizure Drugs GENERALIZED SEIZURE DRUG SPECIAL CONSIDERATIONS Drugs modulate Valproic Acid GABA ▪ Treatment for myoclonic seizure ▪ Valproic Acid ▪ Treatment for absence seizure ▪ Divalproex ▪ Effective in mania, migraine headaches, and complex focal seizures. ▪ Sulfonamide ▪ Reduces abnormal electrical activity in the brain – increases GABA ▪ Acetazolamide activity at inhibitory receptors ▪ Zonisamide Divalproex ▪ Treatment of manic episodes ▪ Treatment of absence and focal seizures ▪ Prevention of migraine headaches ▪ Increase GABA levels in the brain Acetazolamide ▪ Alters electrolyte movement, stabilizing nerve cell membranes ▪ Rarely used to seizure ▪ PO/ IM/ IV Antiseizure Drugs GENERALIZED SEIZURE DRUG SPECIAL CONSIDERATIONS Drugs modulate Zonisamide GABA ▪ Inhibit voltage-sensitive sodium and calcium channels. ▪ Valproic Acid ▪ Stabilizing nerve cell membranes and modulating calcium-dependent ▪ Divalproex presynaptic release of excitatory neurotransmitters. ▪ Sulfonamide ▪ Acetazolamide ▪ Zonisamide Other Medications ▪ Blocking sodium channels Used to Treat ▪ Prevent formation of repetitive action potentials in the abnormal Generalized Seizures functions. ▪ Carbamazepine ▪ Lamotrigine ▪ Levetiracetam ▪ Topiramate Antiseizure Drugs Focal Seizure ▪ Simple or complex FOCAL SEIZURE DRUG SPECIAL CONSIDERATIONS ▪ Clorazepate ▪ Altering sodium or calcium channels ▪ Gabapentin ▪ Increasing activity of GABA – decrease excessive ▪ Felbamate activity ▪ Pregabalin ▪ Lacosamide ▪ Esclicarbazepine ▪ Oxcarbazepine ▪ Rufinamide Antiseizure Drugs Nursing Considerations: ✓ Administer the drug with food to alleviate GI irritation. ✓ Monitor CBC before and periodically during the therapy – to detect and prevent serious bone marrow suppression. ✓ Protect patient from exposure to infection. ✓ Discontinue the drug if patient suffer from adverse effects. ✓ Discontinue the drug slowly, refrain from withdrawing the drug quickly. ✓ Arrange for counseling for patients who become pregnant. ✓ Provide safety measures. ✓ Provide patient teaching. ✓ Suggest patient to wear or carry Medic Alert Band or Bracelet. ✓ Offer support and encouragement to help patient cope with the drug regimen.  Antiseizure Drugs Drugs to treat Generalized Seizure Drugs to treat Focal Seizure Gabapentin Other drugs Felbamate Barbiturates Succinimides Pregabalin Hydantoins Benzodiazepines Drugs Carbamazepine modulate Phenytoin GABA Fosphenytoin Diazepam Clonazepam Valproic Acid Phenobarbital Diazepam Clonazepam Parkinson’s Disease CNS Condition Affected by Antiparkinson’s Drugs Parkinson’s Disease ▪ Progressive, chronic neurological disorder. ▪ Affects adult – middle age, entering their 60s. ▪ Unknown cause ▪ Combination of genetic predisposition and environmental factors contributory factors. ▪ NO CURE FOR PARKINSON’S DISEASE. ▪ Therapy – management of signs and symptoms to provide optimal functioning. ▪ Manifestations: ✓ Lack of coordination ✓ Rhythmic tremors ✓ Rigidity – weakness of the muscles ✓ Trouble maintaining posture or position ✓ Bradykinesia – difficulty performing intentional movements and extreme slowness or sluggishness Parkinson’s Disease ▪ Manifestations: ✓ Shuffling gait ✓ Slow and slurred speech ✓ Masklike expressions ✓ Difficulty swallowing – aspiration pneumonia ✓ Severe cognitive dementia ▪ Parkinsonism – Parkinson’s disease-like extrapyramidal symptoms that are adverse effects of medications, brain tumor, severe carbon monoxide poisoning, CVD, or brain injuries. ▪ Degeneration of the basal ganglia – substantia nigra (nerves secretes dopamine) ▪ Domination of cholinergic or excitatory cells. Antiparkinson’s Drugs Drugs Affecting Parkinson’s Disorders Antiparkinson’s Drugs ▪ Restore the balance between decreasing levels of dopamine and increasing levels of acetylcholine. ▪ Reduces manifested signs and symptoms. ▪ Regain normal function. Dopaminergic Drugs ▪ Increases the effects of dopamine at receptor sites. ▪ Stimulate the dopamine receptors – restore the balance between inhibitory and stimulatory neurotransmitters ▪ Promotes dopamine synthesis ▪ Activate dopamine receptors ▪ Prevent dopamine breakdown ▪ Decrease degradation of levodopa ▪ DO NOT STOP THE PROGRESSION OF PARKINSON’S DISEASE ▪ Provide relief from the manifested signs and symptoms – tremors, rigidity, and bradykinesia Antiparkinson’s Drugs Dopaminergic Drugs DRUG SPECIAL CONSIDERATION Levodopa ▪ Mainstay of treatment for Parkinson’s disease. Carbidopa-Levodopa ▪ This precursor of dopamine crosses the blood brain barrier and converted into dopamine. ▪ Replacement therapy ▪ Carbidopa – protects the levodopa, increasing levels. Amantadine ▪ Antiviral drug ▪ Increase the release of dopamine ▪ Treatment for dyskinesia ▪ Treatment of induced extrapyramidal reactions in adults Apomorphine ▪ Direct dopamine agonists on dopamine receptor sites in the basal Bromocriptine ganglia. Pramipexole Ropinirole Rotigotine ▪ Difficulty swallowing ▪ Transdermal form Antiparkinson’s Drugs Dopaminergic Drugs DRUG SPECIAL CONSIDERATION Rasagiline ▪ Dopamine agonist that increases dopamine in the nerve synapse – area for controlling movement and coordination. Antiparkinson’s Drugs Anticholinergic Drugs ▪ Oppose the effects of acetylcholine at receptor DRUG sites in the basal ganglia. ▪ Benztropine ▪ Restore the chemical balance in the area. ▪ Diphenhydramine ▪ Blocks the cholinergic receptors. ▪ Trihexyphenidyl ▪ Stimulation of the parasympathetic nervous system’s postganglionic effectors. ▪ Useful as adjunctive therapy ▪ For patients who no longer respond to levodopa.  Antiparkinson Drugs Dopaminergic Drugs Anticholinergic Drugs Levodopa Benztropine Carbidopa-Levodopa Diphenhydramine Amantadine Trihexyphenidyl Bromocriptine Rotigotine Antiparkinson’s Drugs Nursing Considerations: ▪ Arrange to decrease the dose of the drug if therapy has been interrupted for any reason to prevent systemic dopaminergic effects. ▪ Evaluate disease progress and signs and symptoms periodically. ▪ Give the drug with meals to alleviate GI irritation. ▪ Monitor bowel functions if constipation is severe. ▪ Monitor urinary output, palpate bladder, and check for residual urine. ▪ Establish safety precaution. ▪ Monitor hepatic, renal, and hematological tests – to detect early signs of dysfunction. ▪ Provide support services and comfort measures. ▪ Provide thorough patient teaching. ▪ Offer support and encouragement. Thanks Do you have any questions? 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