Psychopharmacology and Other Biologic Treatments

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 • 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 thatbreaks 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 • 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 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 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

24. Antipsychotic Medications • Target symptoms: psychosis • Types • Conventional • 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

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: AntimaniaAnticonvulsants • 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. CarbamazepineSide 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 8.11,12Tricyclic: Tertiary Amines • Amitriptyline (Elavil) • Clomipramine (Anafranil) • Doxepine (Sinequan) • Imipramine (Tofranil) • Trimipramine (Surmontil)

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

39. 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

40. 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

41. Serotonin Selective Reuptake InhibitorsSSRI • 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