Core Concepts in Pharmacology Second Edition

1
Drugs for Anxiety and Insomnia
2
Factors that Contribute to Anxiety

• Stressful environment events
• Abnormal fear of a specific situation or object
• Reexperiencing a traumatic life event

3
Nonpharmacological Therapies to Cope with Anxiety

• Behavioral therapy
• Biofeedback techniques
• Meditation

4
CNS Agents Used to Treat Anxiety and Sleep
Disorders

• Antidepressants
• Benzodiazepines
• Barbiturates
• Nonbarbiturates and nonbenzodiazepines

5
Three Types of Antidepressants

• Selective serotonin-reuptake inhibitors (SSRIs)
• Tricyclic antidepressants (TCAs)
• Monoamine oxidase inhibitors (MAOIs)

6
Benzodiazepines

• Short-term treatment of anxiety and sleep
  disorders
• Excessive amounts do not produce
• Respiratory depression
• Coma

7
Barbiturates - Schedule II Drugs

• Rarely used for anxiety or sleep disorders
• Significant side effects
• High risk of psychological and physiological
  dependence

8
Nonbenzodiazepines and Nonbarbiturates

• Anxiety disorders
• Antiseizure medication - valproate (Depakote)
• CNS depressant - buspirone (Buspar)
• Beta blockers - atenolol (Inderal), propanolol
  (Tenormin)
• Insomnia
• Nonbenzodiazepine CNS depressants - zalepon
  (Sonata), zolpidem (Ambien)
• Antihistamines - diphenhydramine (Benadryl),
  hydroxyzine (Vistaril)

9
CNS Depressants

• Slow neuronal activity in the brain
• Low doses cause relaxation to sedation
• High doses cause sleep to anesthesia

10
Antidepressants

• Tricyclic antidepressants - TCAs
• Amitriptyline (Elavil) - depression
• Imipramine (Tofranil) - depression, generalized
  anxiety
• Monoamine oxidase inhibitors - MAOIs
• Phenelzine (Nardil) - social anxiety, depression
• Tranylcypromine (Parnate) - depression

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Antidepressants (contd)

• Selective serotonin reuptake inhibitors - SSRIs
• Fluoxetine (Prozac) - depression, panic, social
  anxiety
• Paroxetine (Paxil) - depression, panic, social
  anxiety
• Atypical antidepressants
• Trazodone (Desyrel) - depression, generalized
  anxiety
• Venlafaxine (Effexor) - depression, social
  anxiety, generalized anxiety

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Benzodiazepines

• Panic disorders
• Alprazolam (Xanax) - generalized anxiety,
  phobias, social anxiety
• Anxiety
• Diazepam (Valium) - panic
• Oxazepam (Serax) - phobias
• Insomnia
• Estazolam (Prosom)
• Flurazepam (Dalmane)
• Triazolam (Halcion)

13
Barbiturates for Sedation and Insomnia

• Short acting
• Pentobarbital sodium (Nembutal)
• Secobarbital (Seconal)
• Intermediate acting
• Amobarbital (Amytal)
• Butabarbital sodium (Butisol)
• Long acting
• Mephobarbital (Mebaral)
• Phenobarbital (Luminal)

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Nonbenzodiazepines, Nonbarbiturates, CNS
Depressants

• Antiseizure medication
• Valproate (Depakote) - panic
• CNS depressants (mild tranquilizers)
• Buspirone (BuSpar) - generalized anxiety, OCD
• Beta blockers
• Atenolol (Tenormin) - performance anxiety, social
  anxiety
• Nonbenzodiazepines
• Zaleplon (Sonata) - insomnia
• Zolpidem (Ambien)

15
Drugs for Emotional and Mood Disorders
16
Categories of Mood Disorders

• Depression
• Bipolar disorder

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Antidepressants Combat Depression

• Enhance mood
• Boost neurotransmitters
• Norepinephrine
• Serotonin
• Four primary classes
• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)
• Atypical antidepressants

18
Several Drugs May Be Used to Manage Bipolar
Disorder

• Mood stabilizers to manage manic phase
• Some antiseizure drugs to stabilize mood
• TCAs and atypical antidepressants used during
  depressive stage
• Benzodiazepines during manic phase to moderate
  manic symptoms
• Antipsychotic agents used for extreme agitation,
  delusions, or hallucinations

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To Manage Attention Deficit-Hyperactivity
Disorder (ADHD)

• CNS stimulants are drug of choice
• Non-CNS stimulants less effective
• Atypical antidepressants and TCAs
• Second choice drugs
• When CNS stimulants fail
• When CNS stimulants are contraindicated

20
Symptoms of ADHD

• Easy distractability
• Failure to receive or follow instructions
  properly
• Inability to focus on one task at a time and
  tendency to jump from one activity to another
• Difficulty remembering

21
Symptoms of ADHD (contd)

• Frequent loss or misplacing of personal items
• Excessive talking and interrupting other children
  in a group
• Inability to sit still when asked repeatedly
• Impulsiveness
• Sleep disturbances

22
Atypical Antidepressants

• Action - inhibit the reuptake of serotonin and
  affect the activity of norepinephrine and
  dopamine
• Primary use - depression
• Examples
• Bupropion (Wellbutrin)
• Nefazodone (Serzone)

23
CNS Stimulants - Schedule II Controlled Substance

• Action - stimulate specific areas of CNS that
  heighten awareness and increase focus
• Primary use - ADHA
• Adverse effects
• Insomnia
• Nervousness anorexia
• Weight loss
• Examples
• Methylphenidate (Ritalin)
• Pemoline (Cykert)

24
Nonstimulants

• Action - inhibit reuptake of norepinephrine
• Primary use - ADHD
• Adverse effects
• Headache
• Insomnia
• Upper abdominal pain
• Decreased appetite
• Cough
• Example - atomoxetine (Strattera)

25
Drugs for Psychoses and Degenerative Diseases of
the Nervous System
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Imbalance of Neurotransmitters in Specific Areas
of the Brain

• Too much dopamine produced
• Stimulates dopamine type 2 (D2) receptors on the
  postsynaptic neurons

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Parkinsonism Symptoms

• Tremor
• Muscle rigidity
• Stooped posture
• Shuffling gait

28
Most Common Degenerative Diseases of the CNS

• Alzheimers disease
• Amyotrophic lateral sclerosis (ALS)
• Huntingtons chorea
• Multiple sclerosis (MS)
• Parkinsons disease

29
Parkinsons Disease Pharmacological Management

• Agents do not cure the disease
• Increase ability to perform normal daily
  activities
• Reduce symptoms of the disease
• Know the side effects of the agents

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Alzheimers Disease Pharmacological Management

• Do not cure the disease
• Slow progression of disease in mild to moderate
  stages (not severe stage)
• Limited effectiveness in improving
• Functions in activities of daily living
• Behavior
• Cognition
• Know the side effects of the different agents

31
Multiple Sclerosis Pharmacological Management

• Do not cure the disease
• Reduce inflammation during exacerbations
• Prevent attacks on the nervous system
• Relieve symptoms
• Know the side effects of different agents

32
Drugs for Parkinsons Disease

• Dopaminergic agents
• Example - levodopa (Larodopa)
• Action - increase dopamine levels in the corpus
  striatum
• Primary use - Parkinsons disease
• Adverse effects - involuntary movements,
  headache, insomnia, nausea, vomiting, orthostatic
  hypotension

33
Drugs for Parkinsons Disease (contd)

• Anticholinergics
• Example - benzotropine (Cogentin)
• Action - acts on CNS
• Primary use - Parkinsons disease
• Adverse effects - dry mouth, blurred vision,
  tachycardia, urinary retention, constipation

34
Drugs for Alzheimers Disease

• Acetylcholinesterase inhibitors
• Example - donepezil (Aricept)
• Action - inhibits acetylcholinesterase which
  intensifies effects of acetylcholine at
  cholinergic receptors in order to improve
  function in activities of daily living, behavior,
  cognition
• Primary use - early stages of Alzheimer's disease
• Adverse effects - nausea, vomiting, diarrhea

35
Drugs for Multiple Sclerosis

• Immunostimulants
• Example - interforon beta la (Avonex)
• Action - decrease overall relapse rate
• Primary use - RRMS
• Adverse effects - redness, pain, swelling,
  itching or lump at injection site, joint pain,
  muscle aches

36
Drugs for Multiple Sclerosis (contd)

• Miscellaneous drugs for symptoms
• Modafinil (Provigil) and amantadine (Symmeterel)
  - fatigue, memory loss, progressive weakness
• Gabapentin (Neurontin) - depression, sensitivity
  to pain
• Methylprednisolone (Solu-Medrol) - acute
  inflammation of CNS

37
Drugs for Pain Control
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Successful Pain Management Depends on

• Accurate assessment of pain experienced
• Potential disorders causing the pain
• Selecting the correct therapy

39
Endogenous Opioids Are Neurotransmitters Released
by Descending Neurons

• Examples - endorphins, dynorphins, enkephalins
• Block the release of substance P in the spinal
  cord
• Pain impulses do not reach the brain

40
Acute Opioid Intoxication

• Medical emergency
• Respiratory depression

41
Naloxone (Narcan) - Opioid Antagonist - Reverses
Respiratory Depression and Other Acute Symptoms
42
Opioid (Narcotic) Analgesics for Pain Management

• Opioid agonists
• Example - morphine
• Mechanisms of action - bind to both mu and kappa
  receptors and produce analgesia, decrease GI
  motility, euphoria, miosis, sedation
• Primary uses - treat severe pain
• Adverse reactions - respiratory depression,
  sedation, nausea and vomiting, and physical and
  psychological dependence

43
Opioid (Narcotic) Analgesics for Pain Management
(contd)

• Opioid antagonists
• Example - naloxone (Narcan)
• Mechanisms of action - inhibit both mu and kappa
  receptors preventing the effects of opioid
  agonists
• Primary uses - opioid overdose, opioid depression
• Adverse effect - drowsiness

44
Opioid (Narcotic) Analgesics for Pain Management
(contd)

• Opioids with mixed agonist-antagonist activity
• Example - pentazocine (Talwin)
• Mechanisms of action - activate kappa receptors
  and block mu receptors to produce analgesia,
  decrease GI motility, miosis, sedation
• Primary uses - treat moderate to severe pain
• Adverse effects - less intense than opioid
  agonists

45
Nonopioid Analgesics

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Examples - aspirin and other salicylates,
  ibuprofen and ibuprofen-like drugs, selective
  COX-2 inhibitors
• Mechanisms of action - aspirin and ibuprofen
  inhibit both COX-1 and COX-2 enzymes which
  inhibit prostaglandins which inhibit pain and
  inflammation selective COX-2 inhibit only COX-2
  enzyme, which produces the prostaglandins that
  cause pain and inflammation
• Primary uses - treat mild to moderate pain,
  inflammation, fever
• Adverse effects - GI irritation and bleeding

46
Nonopioid Analgesics (contd)

• Acetaminophen
• Example - acetaminophen (Tylenol)
• Mechanisms of action - inhibit prostaglandin
  production, then block transmission of pain
  impulse peripherally, inhibits prostaglandins in
  hypothalamus
• Primary uses - treat mild to moderate pain and
  fever
• Adverse effects - very few with recommended doses

47
Nonopioid Analgesics (contd)

• Centrally acting drugs
• Examples - clonidine (Catapres), tramadol
  (Ultram)
• Mechanisms of action - prevents transmission of
  pain impulses in the spinal cord
• Primary uses - management of pain
• Adverse effects - drowsiness, hypotension, nausea