1. Psychopharmacology and Other Biologic Treatments
Chapter 8

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. Pharamacodynamics: Where 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 Interactions with a receptor
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 receptor 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
Specific symptoms for each class of medication
No drug attacks such a target symptom
Side effects - Responses not related to target symptoms (Table 8.1, 8.1).
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 rug 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 8-3)
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. Pharmacokinetics: How 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 another, usually 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
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 process 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

18. Elimination
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 determined by half life
reach steady state in about five times the elimination half-life

20. 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

21. Phases of Drug Treatment
Initiation
Stabilization
Maintenance
Discontinuation

22. Psychiatric Medications
Antipsychotic Medications
Movement Disorders Medication
Mood Stabilizers
Antimania
Antidepressants
Antianxiety and Sedative-Hypnotic
Stimulants

23. Antipsychotic Medications
Target symptoms: psychosis
Types
Conventional
Atypical
Absorption: variable
clinical effects seen 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

24. Antipsychotic Medications
Target symptoms: psychosis
Types
Conventional
Atypical
Absorption: variable
clinical effects seen 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

25. Antipsychotic Medications (cont..)
Preparations
Oral IM
Depot - haloperidol and fluphenazine
Side Effects
Cardiovascular - orthostatic Hypertension
Weight-gain: blocking histamine receptor
Endocrine and sexual: block dopamine, interfere with prolactin
Blood Dyscrasias - agranulocytosis

26. Antipsychotic Medications
Conventional
Phenothiazines (Thorazine, Prolixin)
Thioxanthenes (Navane)
Dibenzoxazepines (Loxitane)
Haloperidol (Haldol)
Atypical or Novel
Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Ziprasidone (Geodon)

27. Antipsychotic Side Effects
Cardiovasular
Anticholinergic
Weight Gain
Endocrine and Side Effects
Blood Disorders
Miscellaneous

28. 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), and tremor, masklike face, loss of spontaneous movements
Akathisia: Inability to sit still, restlessness

29. 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.

30. 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

31. 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

32. 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)

33. 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, cold intolerance.
Avoid during pregnancy.

34. Mood Stabilizers: Antimania Anticonvulsants
Valporate and derivatives (divalproex sodium - Depakote)
Carbamazapine (Tegretol)
Gabapentin (Neurontin) (least side effects)
Lamotrigine (Lamictal)
Topiramate (Topamax)
Highly protein bound
Metabolized by the cytochrome P-540 system
Side effects: dizziness, drowsiness, tremor, visual disturbance, nausea, & vomiting

35. Anticonvulsant Mood Stabilizers
Only carbamazepine is approved for mania.
Used when patients have not responded to lithium
Pharmacokinetics
Highly protein bound, metabolized by P450 system (potential drug-drug interaction)

36. Carbamazepine Side Effects
Dizziness, drowsiness, tremor, visual disturbances, nausea, and vomiting
Minimized by treating in low doses
Give with food
Weight gain
Alopecia (hair loss)

37. Antidepressants Table 8.11,12 Tricyclic: Tertiary Amines
Amitriptyline (Elavil)
Clomipramine (Anafranil)
Doxepine (Sinequan)
Imipramine (Tofranil)
Trimipramine (Surmontil)

38. Antidepressants Secondary Amines
Amoxapine (Asendin)
Desipramine (Norpramin)
Nortriptyline (Aventyl, Pamelor)
Protrypyline (Vivactil)

39. Side Effects -- TCAs Most common uncomfortable side effects Others
sedation
orthostatic hypotension
anticholinergic
Others
tremors,
restlessness, insomnia, confusion
pedal edema, headache, and seizures
Blood dyscrasias
Sexual dysfunction
Adverse
cardiotoxicity

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

41. Serotonin Selective Reuptake Inhibitors SSRI
Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)

42. Side Effects -- SSRIs Headache Anxiety Transient nausea Vomiting
Diarrhea
Weight gain
Sexual dysfunction

43. 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

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

45. Antidepressants Monoamine Oxidase Inhibitors (MAOIs)
Action: Inhibit 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 (Table 18.3)

46. Antianxiety and Sedative-Hypnotic Medication
Used for anxiety, not long-term
Benzodiazepines (Table 8.14)
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

47. Stimulants
Amphetamines
Used in narcolepsy, ADHD, and obesity

48. 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

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