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Psychopharmacology

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Title: Psychopharmacology


1
Psychopharmacology Other Biologic Treatments
  • Chapter 9

2
Psychopharmacology
  • Subspecialty of pharmacology that includes
    medications affecting the brain and behavior used
    to treat mental disorders including
  • Antipsychotics
  • Mood stabilizers
  • Antidepressants
  • Antianxiety medications
  • Stimulants
  • Provides a basis for understanding specific
    biologic treatments of psychiatric disorders

3
PharamacodynamicsWhere Drugs Act
  • Four sites of action
  • Receptors (those sites to which a
    neurotransmitter can specifically adhere to
    produce a change in the cell membranes)
  • Ion channels
  • Enzymes
  • Carrier Proteins
  • Biologic action depends on how its structure
    interacts with a receptor.

4
Receptors
  • Types of Action
  • Agonist same biologic actin
  • Antagonist opposite effect
  • Interactions with a receptor
  • Selectivity specific for a receptor
  • Affinity degree of attraction
  • Intrinsic activity ability to produce a biologic
    response once it is attached to receptor

5
Ion Channels
  • Drugs can block or open the ion channels.
  • Example Benzodiazepine drugs facilitate GABA in
    opening the chloride ion channel.

6
Enzymes
  • Enzymes catalyze specific biochemical reactions
    within cells and are targets for some drugs.
  • Monoamine oxidase is an enzyme that breaks down
    most bioamine neurotransmitters (NE, DA, 5-HT).
  • Enzymes may be inhibited to produce greater
    neurotransmitter effect.

7

Carrier Proteins
  • Transport neurotransmitters across cell membranes
  • Medications may block or inhibit this transport.
  • Example antidepressants

8
Efficacy and Potency
  • Efficacy - Ability of a drug to produce a
    response as a result of the receptors (or
    receptors) being occupied
  • Potency - Dose required to produce the desired
    biologic response
  • Loss of effect
  • Desensitization (rapid decrease in drug effect)
  • Tolerance (gradual decrease in the effect of a
    drug at a given dose)
  • Can lead to being treatment refractory

9
Target Symptoms and Side Effects
  • Target symptoms
  • Specific symptoms for each class of medication
  • No drug attacks such a target symptom
  • Side effects - Responses not related to target
    symptoms (Table 9.1, 9.2).
  • Adverse effects Unwanted effects with serious
    physiologic consequences

10
Drug Toxicity
  • Toxicity Point at which concentrations of the
    drug in the blood stream become harmful or
    poisonous to the body
  • Therapeutic index Ratio of the maximum nontoxic
    dose to the minimum effective dose
  • High therapeutic index Wide range between dose
    at which the drug begins to take effect and dose
    that would be considered toxic
  • Low therapeutic index - low range

11
Absorption
  • From site of administration into the plasma
  • Oral - (tablet and liquid) (Table 9-3)
  • Most convenient
  • Most variable (food and antacids)
  • First pass effect
  • Decreased gastric motility (age, disease,
    medication)
  • IM - Short- and long-acting
  • IV - Rarely used

12
PharmacokineticsHow the Body Acts on the Drug
  • Absorption
  • Distribution
  • Metabolism
  • Elimination

13
Bioavailability
  • Amount of drug that reaches systemic circulation
    unchanged
  • Often used to compare one drug to anotherusually
    the higher the bioavailability, the better

14
Distribution
  • Amount of drug found in various tissues,
    especially the intended ones
  • Psychiatric drugs must pass through blood-brain
    barrier (most fat-soluble).
  • Factors effecting distribution
  • Size of organ ( larger requires more)
  • Blood flow ( more, greater concentration)
  • Solubility (greater, more concentration)
  • Plasma protein (if bound, slower distribution,
    stays in body longer
  • Anatomic barriers (tissues surrounding)

15
Crossing the Blood Brain Barrier
  • Passive diffusion
  • Drug must dissolve in the structure of the cell.
  • Lipid solubility is necessary for drugs passing
    through blood brain barrier (then, can also pass
    through placenta).
  • Binding to other molecules
  • Plasma protein binding
  • The more protein binding, the less drug activity.
  • Can bind to other cells, especially fat cells.
    Then are released when blood level decreases.

16
Metabolism(Biotransformation)
  • Process by which the drug is altered and broken
    down into smaller substances (metabolites) that
    are usually inactive
  • Lipid-soluble drugs become more water soluble, so
    they may be more readily excreted.
  • Most metablism is carried out in the liver.

17
Cytochrome P450
  • Many processes are carried out by enzyme class
    Cytochrome.
  • P-450 high affinity for fat-soluble drugs
  • Involved in metabolism of most psychiatric
    medications
  • Example SSRIs inhibitors of the subfamily
    P-4502D6
  • Pharmacogenomics (pharmacology and genetic
    knowledge)
  • Understanding an individuals genetic makeup
  • Individualizing medications

18
Excretion
  • Clearance Total amount of blood, serum or plasma
    from which a drug is completely removed per unit
    time
  • Half-life Time required for plasma
    concentrations of the drug to be reduced by 50
  • Only a few drugs eliminated by kidneys (lithium)
  • Most excreted in the liver
  • Excreted in the bile and delivered to the
    intestine
  • May be reabsorbed in intestine and re-circulate
    (up to 20)

19
Dosing and Steady State
  • Dosing Administration of medication over time,
    so that therapeutic levels can be achieved
  • Steady-state
  • Drug accumulates and plateaus at a particular
    level.
  • Rate of accumulation is determined by half life.
  • Reach steady state in about five times the
    elimination half-life

20
Individual Variation in Drug Effects
  • Age
  • Ethnicity
  • Polypharmacy

21
Age
  • Alteration in gastric absorption
  • Renal function altered in very young and old
  • Liver metabolism decreases with age

22
Pharmacokinetics Cultural Considerations
  • 9 of whites - genetically defective P-4502D6
  • Asian descent
  • Metabolize ethanol to produce higher
    concentrations of acetaldehyde (flushing,
    palpitations)
  • Require 1/2 to 1/3 dose antipsychotics and more
    severe side effects
  • Cardiovascular effects of propranolol
  • Asian descent - more sensitive
  • African descent - less sensitive

23
Phases of Drug Treatment
  • Initiation
  • Stabilization
  • Maintenance
  • Discontinuation

24
Psychiatric Medications
  • Antipsychotic Medications
  • Movement Disorders Medication
  • Mood Stabilizers
  • Antimania
  • Antidepressants
  • Antianxiety and Sedative-hypnotic
  • Stimulants

25
Antipsychotic Medications
  • Target symptoms psychosis
  • Types typical and atypical
  • Absorption variable
  • Clinical effects seen 30-60 min
  • IM less variable (avoid 1st pass)
  • When immobile, less absorption
  • Metabolism liver
  • Excretion slow
  • Accumulates in fatty tissues
  • 1/2 life of 24 hours or more

26
Antipsychotic Medications (cont.)
  • Preparations
  • Oral
  • IM
  • Depot - haloperidol and fluphenazine
  • Long-acting injectable Risperdal Consta
  • Side Effects
  • Cardiovascular - orthostatic hypertension
  • Weight-gain blocking histamine receptor
  • Endocrine and sexual block dopamine, interfere
    with prolactin
  • Blood dyscrasias - agranulocytosis

27
Antipsychotic Medications
  • Typical
  • Phenothiazines (Thorazine, Prolixin)
  • Thioxanthenes (Navane)
  • Dibenzoxazepines (Loxitane)
  • Haloperidol (Haldol)
  • Atypical
  • Clozapine (Clozaril)
  • Risperidone (Risperdal)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Ziprasidone (Geodon)
  • Aripiprazole (Abilify)

28
Antipsychotic Side Effects
  • Cardiovasular
  • Anticholinergic
  • Weight Gain
  • Endocrine and Side Effects
  • Blood Disorders
  • Miscellaneous

29
Medication-related Movement Disorders Acute
Syndromes
  • Can occur in 90 of all patients
  • Dystonia involuntary muscle spasms, abnormal
    postures, oculogyric crisis, torticollis
  • Parkinsonism rigidity, akinesia (slow movement),
    tremor, masklike face, loss of spontaneous
    movements
  • Akathisia inability to sit still, restlessness

30
Movement Disorders Acute (cont.)
  • Etiology (acute)
  • Related to dopamine in nigrostrial pathway that
    increases cholinergic activity
  • Treatment
  • Anticholinergic medication for dystonia,
    Parkinsonism (Artane and Cogentin)
  • Akathisia does not usually respond to
    anticholinergic medication. Beta blockers have
    best success.

31
Movement Disorders Chronic
  • Tardive Dyskinesia
  • Irregular, repetitive involuntary movements of
    mouth, face and tongue, including chewing, tongue
    protrusion, lip smacking, puckering of the lips
    and rapid eye blinking. Abnormal finger movements
    are common.
  • Symptoms
  • Begin after 6 months, but also as antipsychotics
    are withdrawn
  • Irreversible - controversy

32
Movement Disorders Chronic
  • Etiology
  • Believed that chronic dopamine suppression in the
    EPS causes an overactivation of the system
  • Increases in antipsychotic meds, suppresses
  • Treatment
  • Prevention by using lowest possible dosage,
    minimize use of PRN, closely monitor individuals
    in high-risk groups
  • Monitoring tools

33
Mood Stabilizers Antimania Lithium Carbonate
  • Action uncertain, crosses cell membranes,
    altering sodium transport, not protein bound
  • Side effects thirst, metallic taste, increased
    frequency or urination, fine head and hand
    tremor, drowsiness and mild diarrhea
  • Blood levels monitored (lithium toxicity - severe
    diarrhea, vomiting, drowsiness, muscular weakness
    and lack of coordination, withhold)

34
Lithium Carbonate
  • Monitor creatinine concentrations, thyroid
    hormones and CBC every 6 months.
  • Kidney damage may be a risk.
  • Thyroid function may be altered usually after
    6-18 months. Observe for dry skin, constipation,
    bradycardia, hair loss and cold intolerance.
  • Avoid during pregnancy.

35
Mood Stabilizers Antimania Anticonvulsants
  • Valporate and derivatives (divalproex sodium -
    Depakote)
  • Carbamazapine (Tegretol)
  • Gabapentin (Neurontin) (little support)
  • Lamotrigine (Lamictal)
  • Topiramate (Topamax)

36
Anticonvulsant Mood Stabilizers
  • Used when patients have not responded to lithium
  • Pharmacokinetics
  • Highly protein bound, metabolized by P450 system
    (potential drug-drug interaction)

37
Kindling
  • Repeated electrical stimulation of selected brain
    regions (e.g., amygdala)
  • Stimulation may be subthreshold and work
    cumulatively to produce a mood swing.
  • After a while, stimulation of these areas can be
    brought about by external events, memories, or
    spontaneously.

38
CarbamazepineSide Effects
  • Dizziness, drowsiness, tremor, visual
    disturbances, nausea and vomiting
  • Minimized by treating in low doses
  • Given with food
  • Weight gain
  • Alopecia (hair loss)

39
Antidepressants Table 9-9 Tricyclic Tertiary
Amines
  • Amitriptyline (Elavil)
  • Clomipramine (Anafranil)
  • Doxepine (Sinequan)
  • Imipramine (Tofranil)
  • Trimipramine (Surmontil)

40
AntidepressantsSecondary Amines
  • Amoxapine (Asendin)
  • Desipramine (Norpramin)
  • Nortriptyline (Aventyl, Pamelor)
  • Protrypyline (Vivactil)

41
Side Effects TCAs
  • Most common uncomfortable side effects
  • Sedation
  • Orthostatic hypotension
  • Anticholinergic
  • Others
  • Tremors
  • Restlessness, insomnia, confusion
  • Pedal edema, headache, and seizures
  • Blood dyscrasias
  • Sexual dysfunction
  • Adverse
  • Cardiotoxicity

42
Antidepressants
  • Most antidepressants block the re-uptake of a
    neurotransmitter of one or more of the bioamines
    serotonin, norepinephrine, dopamine.
  • SSRIs - selective to the serotonin

43
Serotonin Selective Reuptake Inhibitors(SSRI)
  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Paroxetine (Paxil)
  • Fluvoxamine (Luvox)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)

44
Side Effects SSRIs
  • Headache
  • Anxiety
  • Transient nausea
  • Vomiting
  • Diarrhea
  • Weight gain
  • Sexual dysfunction

45
SSRIs
  • Usually given in morning, unless sedation occurs
  • Higher doses, especially fluoxetine, can produce
    sedation.
  • Venlafaxine (Effexor), only mildly sedating
  • Paroxetine associated with weight gain

46
Antidepressants Others
  • Mirtazapine (Remeron)
  • Maprotiline (Ludiomil)
  • Trazodone (Desyrel)
  • Nefazodone (Serzone)
  • Bupropion (Wellbutrin)
  • Venlafaxine (Effexor)

47
Antidepressants Monoamine Oxidase Inhibitors
(MAOIs)
  • Action Inhibits enzyme responsible for the
    metabolism of serotonin, dopamine, norepinephrine
    and tyramine
  • Increases levels of norepinephrine and serontonin
    in the CNS
  • Interacts with food low tyramine diet

48
Antianxiety and Sedative-Hypnotic Medication
  • Used for anxiety, not long-term
  • Benzodiazepines (Table 9.11)
  • Diazepam (Valium)
  • Lorazepam (Ativan)
  • Alprazolam (Xanax)
  • Nonbenzodiazepines
  • Busipirone (BuSpar)
  • Zolpidem (Ambien)
  • Side effects
  • Sedation and CNS depression
  • Tolerance and dependence (Benzos)
  • Avoid Benzo in elderly

49
Stimulants
  • Amphetamines
  • Used in narcolepsy, ADHD and obesity

50
Electroconvulsive Therapy
  • Initiate generalized seizures by an electrical
    current
  • Short-acting anesthetic and muscle relaxant given
  • Repeat procedure 2-3 times per week.
  • Produces rapid relief of depressive symptoms
  • Side effects hypo- or hypertension, bradycardia
    or tachycardia, and minor arrhythmias immediately
    after

51
Other Biological Treatment
  • Light Therapy (Phototherapy)
  • Reset circadian rhythms
  • Used for SAD
  • Nutritional Therapies
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