Nursing 220: Pharmacology Module V: Central Nervous System and Psychotropic Drugs

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Nursing 220 PharmacologyModule V Central
Nervous System and Psychotropic Drugs

• Presented by
• Ronda M. Overdiek, MSN, CCRN, RNC

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Overview

• Chapters 20-35
• CNS Pharmacology (20)
• Parkinsons Disease (21)
• Alzheimers Disease (22)
• Epilepsy (23)
• Muscle spasm/Spasticity (24)
• Local Anesthetics (25)
• Opioid (Narcotic) Analgesics (27)
• Sedative/Hypnotic Drugs (33)
• Antipsychotic Agents (30)
• Antidepressants (31)
• Bipolar Drugs (32)
• CNS Stimulants (35)

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Introduction to Central Nervous System
Pharmacology

• CNS Drugs
• Agents that act on the brain and spinal cord
• Medical Purposes
• Psychiatric disorders
• Suppression of seizures
• Relief of pain
• Production of anesthesia
• Non Medical purposes
• Stimulant
• Depressant
• Euphoriant
• Mind altering abilities

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Introduction to Central Nervous System
Pharmacology

• Peripheral Nervous System Neurotransmitters
• Acetylcholine, norepinephrine, epinephrine
• Central Nervous System Neurotransmitters (Table
  20-1 page 168)
• Norepinephrine, epinephrine, dopamine, serotonin,
  aspartate, glutamate, GABA, glycine, dynorphines,
  endorphins, enkaphalins, neurotensin,
  somatostatin, substance P, oxytocin, vasopressin,
  acetylcholine, histamine

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Introduction to Central Nervous System
Pharmacology

• Blood Brain Barrier
• Impedes the entry of drugs into the brain
• Passage is limited to lipid-soluble agents and to
  drugs that are able to cross by way of specific
  transport systems
• Drugs cannot cross if they are protein bound and
  are highly ionized

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Introduction to Central Nervous System
Pharmacology

• Adaptation of CNS to prolonged drug exposure
• Increased therapeutic effects
• Decreased side effects
• Tolerance
• Physical dependence

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Chapter 21Parkinsons Disease Drugs

• Parkinson Disease
• Degenerative disorder of the basal ganglia
  involving the depletion of the inhibitory
  neurotransmitter dopamine.
• Imbalance of dopaminergic (inhibitory) and
  cholinergic (excitatory) activity causes
  symptoms. Balance of the two produced normal
  motor function.
• Possible Causes
• Genetic, viral, and toxic.

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Chapter 21Parkinsons Disease Drugs

• Parkinson Disease
• Clinical Manifestations
• Tremors at rest, rigidity (muscle stiffness),
  akinesia (decrease in voluntary
  movements-disturbance in time it takes to make a
  movement), postural abnormalities.
• Associated with depression and dementia.
• Treatment Drug therapy

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Chapter 21Parkinsons Disease Drugs

• Goal of drug treatment
• Improve the patients ability to carry out
  activities of daily life.
• Only provide symptomatic relief they do not cure
  PD nor do they alter disease progression.
• Give drugs that restore the functional balance
  between dopamine and ACh.
• Dopaminergic agents activate dopamine receptors
• Anticholinergic agents drugs the block receptors
  for ACh.

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Chapter 21Parkinsons Disease Drugs

• Table 21-1 Dopaminergic Agents
• Dopamine Replacement
• Promotes dopamine synthesis
• Levodopa/Carbidopa
• Dopamine Agonists
• Stimulate dopamine receptors directly
• COMT Inhibitors
• Enhance the effects of levodopa by blocking its
  degradation
• Dopamine Releaser
• Promotes dopamine release
• MAO-B Inhibitors
• Inhibits dopamine breakdown

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Chapter 21Parkinsons Disease
DrugsDopaminergic Agents

• Levodopa
• Reduces symptoms
• Beneficial effects of the drug diminish over time
• Conversion of levodopa to dopamine takes place
  following the uptake in the dopaminergic nerve
  terminals after it crosses the blood brain
  barrier and enters the brain.
• Dopamine itself cannot cross the blood brain
  barrier
• Side Effects Nausea/vomiting, dyskinesias
  (movement disorders-head bobbing, tics,
  grimacing), hypotension, dysrhythmias, psychosis
  (visual hallucinations, nightmares, paranoid
  ideation), darken sweat and urine.

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Chapter 21Parkinsons Disease
DrugsDopaminergic Agents

• Levodopa plus Carbidopa Sinemet
• Carbidopa is used to enhance the effects of
  levodopa
• Inhibits decarboxylation of levodopa at the
  intestine and peripheral tissues, making levodopa
  more available to the CNS.
• Carbidopa allows the dosage of levodopa to be
  reduced by 75
• Reduces cardiovascular and other side effects of
  levodopa

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Chapter 21Parkinsons Disease DrugsDopamine
Agonists

• Used in younger patients (first-line drugs)
• For patients with mild/moderate symptoms
• Contrast to levodopa
• Dont depend on enzymatic conversion to become
  active
• Are not converted to potentially toxic
  metabolites
• Dont compete w/ dietary proteins for uptake from
  intestine or transport across the blood-brain
  barrier
• Lower incidence of response failures
• Less likely to cause disabling dyskinesias
• However, do cause more serious side effects
• Hallucinations, daytime sleepiness, postural
  hypotension

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Chapter 22Alzheimers Disease Drugs

• Alzheimer Disorder
• Cause is unknown
• Loss of neurotransmitter stimulation, chromosomal
  mutations, viral causes, etc.
• Pathophysiology
• Neuronal proteins become distorted and twisted
  causing degeneration and development of plaques
  (senile plaques) causing decrease in neuronal
  transmission.

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Chapter 22Alzheimers Disease Drugs

• Alzheimer Disease
• Clinical Manifestations
• Forgetfulness, emotional upset, disorientation,
  confusion, behavioral changes (irritability,
  agitation, restlessness), deterioration of
  language, rigidity, posturing.
• Treatment
• Memory aids, assisting with ADLs.

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Chapter 22Alzheimers Disease Drugs

• Patients w/advanced AD have acetylcholine levels
  that are 90 below normal.
• Drug treatment
• Cholinesterase Inhibitors
• Prevent breakdown of ACh by acetyl
  cholinesterase, increasing the availability of
  ACh at cholinergic synapses.
• Patients w/mild to moderate symptoms only 25-30
  respond
• Vitamin E / Selegiline (antioxidant properties)
• Nonsteroidal Anti-inflammatory Drugs

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Chapter 23Drugs for Epilepsy

• Epilepsy
• Refers to a group of disorders characterized by
  excessive excitability of neurons within the CNS
  producing a variety of symptoms ranging from
  brief periods of unconsciousness to violent
  convulsions.
• Treatment
• Antiepileptic drugs

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Chapter 23Drugs for Epilepsy

• Antiepileptic Drugs work by three mechanisms
• Suppression of sodium influx
• AEDs bind to sodium channels while they are in
  an inactivated state, prolonging channel
  inactivation, thereby delaying return to the
  active state which decreases the ability of the
  neurons to fire at high frequency.
• Suppression of calcium influx
• Inhibit calcium influx through T-type calcium
  channels which are large enough in the
  hypothalamus to cause an action potential which
  can result in absent (Petit Mal) seizures.
• Potentiation of GABA
• GABA is an inhibitory neurotransmitter that is
  widely distributed throughout the brain.
  Augmentation of GABA decreases neuronal
  excitability and suppresses seizure activity.

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Chapter 23Drugs for Epilepsy

• Drug Administration Considerations
• Goal reduce seizures to an extent that enables
  the patient to live a normal or near-normal life.
• Proper drug selection for specific seizure
  disorders
• Drug evaluation for effectiveness
• Monitoring plasma drug levels
• Promoting compliance
• Withdrawing antiepileptic drugs

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Chapter 23Drugs for Epilepsy

• Phenytoin (Dilantin)
• Most widely used AED
• Used for partial seizures and primary generalized
  tonic-clonic seizures
• Causes selective inhibition of sodium channels
• Capacity of the liver to metabolize phenytoin is
  very limited. Plasma levels need to be
  monitored-narrow therapeutic range.

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Chapter 23Drugs for Epilepsy

• Carbamazepine (Tegretol)
• Active against partial and tonic-clonic seizures
• Causes selective inhibition of sodium channels
• Valproic Acid (Depakote)
• Used to treat all major seizure types as well as
  bipolar disorder and prevention of migraine
  headaches.
• Acts by all three mechanisms inhibition of
  sodium channels, suppresses calcium influx,
  augments inhibitory influence of GABA

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Chapter 23Drugs for Epilepsy

• Ethosuximide (Zarontin)
• Drug of choice for absent seizuresused only for
  absent seizures
• Inhibition of low-threshold calcium currents
• Phenobarbital
• Classified as an anticonvulsant barbiturate
• Active against partial seizures and generalized
  tonic-clonic seizures
• Potentiates the effects of GABA

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Chapter 24Drugs for Muscle Spasm and Spasticity

• Muscle spasm
• Involuntary contraction of a muscle or muscle
  group (resulting from muscle injury)
• Drug therapy
• Analgesic anti-inflammatory agents
• Centrally acting muscle relaxants
• Used to treat localized spasm resulting from
  muscle injury, decreasing local pain and
  tenderness and increasing range of motion
• Treatment is almost always associated w/sedation
• No studies indicating the superiority of one drug
  over another, drug selection is based on
  prescribers preference and patients response.

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Chapter 24Drugs for Muscle Spasm and Spasticity

• Spasticity
• Refers to a group of movement disorders of CNS
  origin characterized by heightened muscle tone,
  spasm, and loss of dexterity.
• Causes include multiple sclerosis and cerebral
  palsy
• Drug Treatment
• Baclofen/Diazepam act in the CNS
• Dantrolene acts on the skeletal muscle

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Chapter 25Local Anesthetics

• Local anesthetics
• Drugs that suppress pain by blocking impulse
  conduction along axons (by blocking sodium
  channels)
• Pain can be suppressed w/o causing generalized
  depression of the entire nervous system
• Administration
• Topical applying directly to skin or mucous
  membranes
• Injection Infiltration, nerve block, intravenous
  (regional) epidural, spinal anesthesia.

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Chapter 25Local Anesthetics

• Two major groups Amides / Esters
• Amide Prototype Lidocaine
• Administered topically and by injection
• Can be administered w/epinephrine
• Amount of drug monitored, toxicity can result
• Ester Prototype Procaine (Novocain)
• Administered by injectionnot effective topically
• Poses a greater risk of allergic type reactions
• Ester Cocaine
• Excellent local anestheticadministration is
  topical

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Chapter 27 Narcotic Analgesics

• Analgesics
• Drugs that relieve pain without causing loss of
  consciousness
• Opioid Analgesics
• Name derived from opium
• Morphine, Codeine, oxycodone
• Opioid is a general term defined as any drug,
  natural or synthetic, that has actions similar to
  those of morphine.

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Chapter 27 Narcotic Analgesics

• Opioid Receptors
• Mu Receptors
• Responses to activation of mu receptors include
  analgesia, respiratory depression, euphoria, and
  sedation.
• Opioid analgesics act primarily through
  activation of mu receptors
• Kappa receptors
• Responses to activation of kappa receptors can
  produce analgesia and sedation.
• Opioid analgesics produce weak activation of
  kappa receptors
• Delta receptors
• Opioid analgesics do NOT interact with delta
  receptors
• Endogenous opioid peptides (enkephalins,
  endorphins, and dynorphins) react w/ all three
  receptors

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Chapter 27 Narcotic Analgesics

• Classifications of Drugs
• Analgesics are classified on the basis of how
  they affect receptor function
• At each type of receptor, a drug can act in one
  of three ways
• Agonist
• Partial Agonist
• Antagonist

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Chapter 27 Narcotic Analgesics

• Pure Opioid Agonists
• Activate mu and kappa receptors producing
  analgesia, euphoria, sedation, respiratory
  depression, etc. Can be subdivided into moderate
  or strong opioid agonists.
• Agonist-Antagonist Opioid
• When administered alone, produce analgesia
• When administered w/ opioid agonist, it can
  antagonize analgesia caused by the pure agonist.
• Pure Opioid Antagonists
• Act as antagonists at mu and kappa receptors
• Used for reversal of respiratory and CNS
  depression caused by overdose with opioid agonists

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Chapter 27 Narcotic Analgesics

• Pure Opioid Agonist (Strong) Prototype
  Morphine
• Therapeutic use pain
• Mimics the actions of endogenous opioid peptides
  primarily at mu receptors.
• Adverse effects respiratory depression,
  constipation, orthostatic hypotension, urinary
  retention, elevation of ICP, sedation, etc.
• Considerations
• Tolerance and physical dependence
• Other Strong Opioid Agonists
• Fentanyl, Meperidine (Demerol), Heroin.

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Chapter 27 Narcotic Analgesics

• Pure Opioid Agonist (Moderate to Strong)
• Similar to morphine, they produce analgesia,
  sedation, euphoria and can cause respiratory
  depression, constipation, urinary retention, etc.
  
• Differences are primarily quantitativethey
  produce less analgesia and respiratory depression
  than morphine and have a lower potential for
  abuse.
• Prototypes
• Codeine, oxycodone (percodan, percocet),
  hydrocodone (Vicodin), propoxyphene (Darvon).

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Chapter 27 Narcotic Analgesics

• Agonist-Antagonist Opioids
• Prototype Pentazocine (Talwin)
• Acts as an agonist at kappa receptors
• Acts as an antagonist at mu receptors
• Respiratory depression is limited
• If a patient is physically dependent on a pure
  opioid agonist, administration of an
  agonist-antagonist opioid will cause withdrawal.
• Nalbuphine (Nubain), Butorphanol (Stadol)

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Chapter 27 Narcotic Analgesics

• Opioid Antagonists
• Block the effects of opioid agonists
• Used for overdose, reversal of postoperative
  opioid effects and management of opioid
  addiction.
• Naloxone (Narcan)
• It is a competitive antagonist at opioid
  receptors reversing analgesia, sedation,
  euphoria, respiratory depression.
• Need to know pharmacokinetics to monitor patients
• Naltrexone (Re Via, Depade)
• Pure opioid antagonist approved for treating
  opioid abuse and alcohol abuse. Blocks euphoria
  experienced by the abuser

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Chapter 27 Narcotic Analgesics

• Nursing Considerations
• Assessment of pain
• Dosage determination
• Dosing schedule
• Avoiding withdrawal
• Physical dependence, abuse, and addiction as
  clinical concerns

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Chapter 33Sedative-Hypnotic Drugs

• Sedative-hypnotic drugs
• Depress CNS function
• Primarily used to treat anxiety and insomnia
• Before benzodiazepines
• General CNS depressants (barbiturates) were
  utilized to treat anxiety and insomnia.
• Powerful respiratory depressants-prove fatal in
  overdose
• Have a high potential for abuse
• With prolonged abuse they produce significant
  tolerance and physical dependence
• Induce synthesis of hepatic drug-metabolizing
  enzymes, decreasing responses to other drugs

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Chapter 33Sedative-Hypnotic Drugs

• Benzodiazepines
• Drugs of choice for treating anxiety/insomnia
• Used to induce general anesthesia and manage
  seizure disorders, muscle spasms, panic
  disorders, and alcohol withdrawal.
• Prototypes Diazepam (Valium) Lorazepam
  (Ativan) Alprazolam ( Xanax).
• Potentiate (amplify) the actions of
  GABA-inhibitory neurotransmitter found in the CNS
• Pharmacologic Effects
• Effects progress from sedation to hypnosis to
  stupor. Reduce anxiety, promote sleep, induce
  muscle relaxation.
• Considerations produce confusion, amnesia,
  hypotension cardiac arrest (IV administration).
  They are weak respiratory depressants.
• Overdose
• Treatment w/Flumazenil (Romazicon) competitive
  benzodiazepine receptor antagonistadverse effect
  is precipitation of convulsions.

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Chapter 33Sedative-Hypnotic Drugs

• Barbiturates
• Cause nonselective depression of CNS function and
  are the prototypes of the general CNS
  depressants.
• Used for sedation, induction of sleep,
  suppression of seizures, general anesthesia.
• Have a high abuse potential, are subject to
  multiple drug interactions, cause tolerance and
  dependence, and are powerful respiratory
  depressants.
• Barbiturates directly mimic GABAtherefore there
  is no ceiling to the degree of CNS depression
  they can produce.
• Examples Phenobarbital, secobarbital, thiopental.

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Chapter 30Antipsychotic Agents Schizophrenia

• Antipsychotic Agents
• A chemically diverse group of compounds employed
  to treat a broad spectrum of psychotic disorders.
• Schizophrenia, delusional disorders, acute mania,
  depressive psychoses, drug induced psychoses.
• Two major groups
• Conventional Antipsychotics
• Block receptors for dopamine in the CNS
• Atypical Antipsychotics
• Only produce moderate blockage of receptors for
  dopamine and much stronger blockade of receptors
  for serotonin

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Chapter 30Antipsychotic Agents Schizophrenia

• Schizophrenia
• Chronic psychotic illness characterized by
  disordered thinking and a reduced ability to
  comprehend reality.
• Positive symptoms
• Hallucinations, delusions, disordered thinking,
  disorganized speech, combativeness, agitation,
  paranoia
• Negative symptoms
• Social/emotional withdrawal, lack of motivation,
  poverty of speech, blunted affect, poor insight,
  poor judgment, poor self-care
• Etiology is unknown

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Chapter 30Antipsychotic Agents Schizophrenia

• Conventional Antipsychotic Group Properties
• Because of extrapyramidal side effects (serious
  movement disorders- Page 286) they are known as
  neuroleptics.
• Classified by potency (low, medium, high) or by
  chemical structure.
• Mechanism of Action
• Varying degrees these drugs block receptors for
  dopamine, acetylcholine, histamine, and
  norepinephrine.
• Relief of positive symptoms respond better to
  conventional antipsychotic drugs less effect on
  negative symptoms

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Chapter 30Antipsychotic Agents Schizophrenia

• Conventional Antipsychotics
• Low potency Prototype Chlorpromazine
  (Thorazine)
• Use Schizophrenia and other psychotic disorders,
  manic phase of bipolar disorder, suppression of
  emesis and relief of intractable hiccups.
• High Potency Prototype Haloperidol (Haldol)
• Can cause more early extrapyramidal symptoms
  (EPS) but less sedation, orthostatic hypotension.
  Preferred for initial therapy.
• Use Schizophrenia and acute psychosis,
  Tourettes syndrome.

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Chapter 30Antipsychotic Agents Schizophrenia

• Atypical Antipsychotic Agents
• Cause few or no EPS, can relieve both positive
  and negative symptoms of schizophrenia.
• Prototype Clozapine (Clozaril)
• Use Schizophrenia
• Blocks receptors for dopamine and serotonin

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Chapter 31Antidepressants

• Antidepressants
• Used to relieve symptoms of depression as well as
  help patients with anxiety disorders
• Four major groups
• Tricyclic antidepressants
• Selective serotonin reuptake inhibitors
• Monoamine oxidase inhibitors
• Atypical antidepressants
• Depression
• Symptoms depressed mood and loss of pleasure or
  interest in all or nearly all of ones usual
  activities and past times. Can include insomnia,
  anorexia, weight loss, weight gain, mental
  slowing, loss of concentration, feelings of
  guilt, worthlessness and helplessness, thoughts
  of death and suicide and overt suicidal behavior.

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Chapter 31Antidepressants

• Tricyclic Antidepressants (TCAs)
• Prototype Imipramine
• Mechanism of Action
• Block neuronal reuptake of norepinephrine and
  serotonin which intensifies their effects
• Uses Depression, bipolar disorder
• Considerations onset of the blockade and the
  onset of therapeutic response can be lengthy.
  Initial responses develop in 1-3 weeks maximal
  responses over 1 to 2 months.

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Chapter 31Antidepressants

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Most commonly prescribed group of antidepressants
• As effective as TCAs but do not cause
  hypotension, sedation, or anticholinergic effects
  (dry mouth, blurred vision, photophobia,
  constipation, urinary hesitancy, tachycardia).
• Use major depression/ Table 31-4
• Prototype Fluoxetine (Prozac, Sarafem)
• Mechanism of action
• Produces selective inhibition of serotonin
  reuptake
• Blockade of transmitter uptake occurs quickly,
  therapeutic effects are the result of adaptive
  cellular changes that take place in response to
  prolonged uptake blockade
• Other SSRIs Celexa, Paxil, Zoloft

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Chapter 31Antidepressants

• Monoamine Oxidase Inhibitors (MAOIs)
• Most dangerous risk of triggering hypertensive
  crisis by eating foods rich in tyramine (Table
  31-5 page 312)
• MAO is an enzyme found in the liver, the
  intestinal wall, and terminals of
  monoamine-containing neurons. Their function is
  to convert NE, serotonin, and dopamine into
  inactive products. MAO inhibitors block this
  process.
• Uses depression, bulimia, obsessive-compulsive
  disorder, reduce panic attacks
• Caution many drug interactions

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Chapter 31Antidepressants

• Atypical Antidepressants
• Bupropion (Wellbutrin)
• Stimulant actions and also suppresses appetite
• Mechanism by which depression is relieved is
  unclear but appears to blockade dopamine uptake.
• Others Effexor, Serzone, Remeron, Trazadone.

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Chapter 32Drugs for Bipolar Disorder

• Bipolar Disorder
• Severe biologic illness characterized by
  recurrent fluctuations in mood either the mood
  is abnormally elevated or depressed.
• Drug therapy
• Mood stabilizers
• Antidepressants (used w/mood stabilizer)
• Antipsychotics (used w/mood stabilizer)

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Chapter 32Drugs for Bipolar Disorder

• Mood Stabilizing Drugs
• Provide relief from an acute manic or depressive
  episode, preventing symptoms from recurring.
• Prototype Lithium
• Low therapeutic index so levels MUST be monitored
  (toxicity can occur at blood levels that are only
  slightly greater than therapeutic).
• Although lithium has been studied extensively,
  the precise mechanism by which it stabilized mood
  is unknown.

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Chapter 32Drugs for Bipolar Disorder

• Mood Stabilizing Anticonvulsants
• Prototype Valproic acid (Depakene, Depakote)
• It is the only antiseizure agent that has been
  approved by the FDA for treatment of BPD.
• It is as effective as lithium, works faster, and
  has a higher therapeutic index and more desirable
  side effect profile.
• First line treatment for BPD

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Chapter 35CNS Stimulants

• CNS stimulants
• Increase the activity of CNS neurons.
• In sufficient doses, all CNS stimulants can cause
  convulsions.
• Indications
• Attention deficit/hyperactivity disorder (ADHD)
• Narcolepsy
• Groups
• Amphetamines
• Methyphenidate
• Methylxanthines

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Chapter 35CNS Stimulants

• Amphetamines
• Act primarily by promoting release of and partly
  by inhibiting reuptake of both norepinephrine and
  dopamine.
• Effects increase wakefulness and alertness,
  reduce fatigue, elevate mood, augment
  self-confidence and initiative. Augment euphoria,
  talkativeness and increased motor activity.
  Stimulate respiration and suppress appetite and
  perception of pain.
• Physical dependence can resulthigh potential for
  abuse
• Uses ADHD, narcolepsy, obesity.

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Chapter 35CNS Stimulants

• Methylphenidate (Ritalin)
• Promote NE and dopamine release and inhibition of
  NE and dopamine reuptake
• Uses ADHD and narcolepsy
• Chemically structured different from amphetamines

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Chapter 35CNS Stimulants

• Methylxanthines
• Prototype Caffeine
• Decreases drowsiness and fatigue and increases
  capacity for prolonged intellectual exertion
• Uses
• Neonatal apnea, promoting wakefulness, relief of
  headaches

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Questions?