Behavioral Aspects of Medicine - Exam 2

• ADME
• Absorption, Distribution, Metabolism, Excretion

Movement of a drug from its site of administration into the central compartment/bloodstream

from the blood stream to interstitial and intracellular fluids

In most cases, biotransformation reactions generate more polar metabolites that are readily excreted from the body

The kidney is the most important organ for excreting drugs and their metabolites

The time needed to clear 50% of drug from plasma. After 4 half lives, elimination is 94% complete.

Amount of drug in the body divided by the concentration in the blood.

• (enzymes)
• increases rate of metabolism.
• Result = decreased duration & intensity of drug action.
• Cytochrome P450 Monooxidase (CYP-450) System of Drug Metabolism
• Caffeine, omeprazole, smoking, Carbamazepine (Tegretol), Phenobarbital, Phenytoin, Ritonavir, Oxcarbazepine, Modafinil, Topiramate, St John’s wort

• (enzymes)
• decreases rate of metabolism.
• Result = increased duration & intensity of drug action.
• Cytochrome P450 Monooxidase (CYP-450) System of Drug Metabolism
• PAROXETINE (Paxil)
• FLUOXETINE (Prozac)
• BUPROPRION (Welbutrin)
• SERTRALINE (Zoloft)

• Cell membrane proteins that are stimulated by specific neurotransmitters
• receptors:
• PROTEIN KINASE
• ION CHANNELS
• G PROTEIN COMPLEXES

• Cholinergic
• Monoamines
• Neuropeptides
• Amino acids

• (Neurotransmitters)
• (ACH (Acetylcholine))
• MUSCARINIC RECEPTORS
• NICOTINIC RECEPTORS

• (Neurotransmitters)
• Catecholamines (Dopamine, Norepinephrine, Epinephrine)
• Serotonin
• Histamine

• (Neurotransmitters)
• eg: Opioids (endorphins)

• (Neurotransmitters)
• GABA, Glycine: Inhibitory
• Glutamate, Aspartate: Excitatory

• Antidepressants
• Antipsychotics
• Mood Stabilizers
• Anti-anxiety agents (anxiolytics)
• Psychostimulants
• Dementia Drugs
• Antiparkinsonians
• Medications for Treatment of Substance Dependence

Increase serotonin at brain neurons by blocking serotonin reuptake, long-term possibly effect receptor numbers and distribution.

• Inhibit the action of MAO-A and B enzymes that metabolize: 5-HT (serotonin), DA (dopamine), NE (norepinephrine).
• Dietary restriction - Must be tyramine-free throughout Tx and for 2wks after D/C of med (fermented/aged foods, red wine, caution with chocolate and caffeine)

Bind to the BDZ-GABA-Cl receptor complex, facilitating the action of GABA (inhibitory neurotransmitter) on CNS excitability.

• Antagonism of dopamine receptors.
• Typical, atypical (novel)

• SSRIs (Selective Serotonin Reuptake Inhibitors)
• SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
• TCAs (Tricyclics) {or heterocyclics}
• MAOIs (Monoamine Oxidase Inhibitors)
• Others

• Lithium - monitor kidney function
• Valproic Acid (Depakote)
• Carbamazepine (Tegretol) - bad in pregnancy
• Lamotrigine (Lamictal)

• Benzodiazepines (diazepam, lorazepam, alprazolam)
• Non-Benzodiazepine (buspirone)

• Diagnosis
• Symptoms
• Risks / Benefits
• Alternative Treatments
• Comorbid Medical Diagnoses
• Concurrent Treatments, including: OTC, herbal, & supplement preparations

• Previous Response / Tolerability
• Family History
• Comorbid Psychiatric Symptoms
• Comorbid Psychiatric Diagnoses
• Comorbid Medical Diagnoses
• Concurrent Treatments

Tx with SSRI, clomipramine (Anafranil, a TCA), or SNRI usually first choice.

• avoid trazodone and bupropion
• because they are relatively ineffective for panic. Start Tx w/: paroxetine (Paxil), sertraline (Zoloft), venlafaxine (Effexor).

avoid TCAs.

• Agoraphobia
• Borderline Personality Disorder
• Depression (unipolar / bipolar)
• Dysthymic Disorder
• Generalized Anxiety Disorder (GAD)
• Hypochondriasis
• Obsessive-Compulsive Disorder
• Panic Disorder
• Premenstrual Dysphoric D/O (PMDD)
• Post-Traumatic Stress Disorder (PTSD)
• Schizoaffective Disorder
• Social Phobia

• maximum daily dose
• major depressive disorder

• tardive dyskinesia – involuntary movements especially of lower face (tongue thrusting, dry lips)
• Lower risk of TD with newer (atypical/novel) antipsychotics

• ExtraPyramidal Symptoms – atypical involuntary muscle contraction (gait, movement, posture)
• Lower ESP with newer (atypical/novel) antipsychotics

• Increased with all antipsychotics, except clozapine, ziprasidone, aripiprazole and (maybe) quetiapine.
• SSRIs, particularly paroxetine, may also increase prolactin and exacerbate neuroleptic-induced prolactinemia.

• well tolerated
• quick onset
• effective
• safe in overdoes
• low cost

• withdrawal reactions
• sedation
• risk of abuse
• poor antidepressant effect

• effective
• relatively safe
• no risk of abuse
• effective on depression

• possible increase in anxiety during initial period of use
• not for immediate symptomatic relief
• sexual side effects
• other side effects - insomnia/sedation, headache, GI upset, anxiety, agitation

• Psychoanalysis
• Brief Psychodynamic Psychotherapy
• Group Psychotherapy
• Family Therapy & Couples Therapy
• Behavior Therapy
• Dialectical Behavior Therapy
• Cognitive Therapy
• Cognitive-Behavior Therapy
• Hypnosis
• Biofeedback
• Interpersonal Therapy

• (ECT)
• Induction of a bilateral generalized seizure.
• Adverse cognitive effects: confusion, disorientation, memory loss.
• These are (mostly) reversible.
• Newer developments in technique decrease adverse effects, offer potential for better acceptance among clinicians & patients.
• First performed in 1938.
• Still the fastest & most effective Tx for Major Depressive D/O.
• For pts. who have failed med trials, not tolerated meds, severe or psychotic syx, are acutely suicidal or homicidal, or have marked syx of agitation or stupor.
• (intractable, refractory depression)
• other indications: schizophrenia, bipolar mania, catatonia
• Contraindication - increased intracranial pressure (space occupying lesion)

cutting the corpus callosum to disconnect the two hemispheres of the brain, for control of intractable seizures

• Refers to many states in which the sufferer experiences a sense of impending threat or doom that is not well defined or realistically based.
• Can be: Adaptive or Pathologic;
• Can be: Transient or Chronic;
• Variety of psychological & physical manifestations.

• Most common group of psychiatric illnesses in U.S.
• > 23 million people affected every year (approx. 7.3 % of population)
• Heterogeneous group of disorders in which feeling of anxiety is the major element.

• Panic d/o w/ agoraphobia
• Panic d/o w/o agoraphobia
• Agoraphobia
• Social phobia
• Specific phobia
• Obsessive-Compulsive d/o
• Generalized Anxiety d/o
• Acute Stress d/o
• Posttraumatic Stress d/o
• Substance-induced Anxiety d/o
• Anxiety d/o due to a general medical condition
• Anxiety d/o NOS

• Recurrent unexpected panic attacks.
• Seen w/ or w/o agoraphobia.
• Twice as common in women,
• Lifetime prevalence 2% to 3%.
• Typical onset in 20s, most cases begin before age 30.
• > 60% comorbid depression.

• Typically come on suddenly,
• Peak within minutes,
• Last 5 to 30 minutes.

• 1 of these must occur x > 1 month:
• Persistent concern about having additional attacks
• Worry about the implications of the attacks (losing control, “going crazy”)
• Significant change of behavior related to attacks (restrict activities)
• Plus 4 of 13 typical symptoms:
• Palpitations, pounding heart
• Sweating
• Trembling, shaking
• Sensation of SOB or smothering
• Feeling of choking
• Chest pain/discomfort
• Nausea or abdominal distress
• Feeling dizzy, unsteady, lightheaded, faint
• Derealization or depersonalization
• Fear of losing control, going crazy
• Fear of dying
• Paresthesias
• Chills or hot flashes

• until proven otherwise
• (think of general medical conditions before psychiatric UPO)
• EKG/bloodwork to rule out cardiac issues or drug abuse before moving onto psychiatric causes for symptoms

cognitive behavioral therapy

• Women > Men
• Lifetime prevalence: 25%
• Typical onset in childhood, most occur before age 12.
• Tend to run in families
• ?Learned – paired w/ traumatic events
• Intense fear of particular objects or situations (snakes, heights).
• It is the most common psych d/o.
• Tend to remit spontaneously w/ age
• In adulthood often become chronic.
• Rarely cause disability
• Tx: systematic desensitization

• (social anxiety disorder)
• Intense fear of being scrutinized in social or public situations
• May be generalized or limited to specific situations.
• Men = Women
• Prevalence of 3% to 5%
• Typical onset in adolescence, most occur before age 25.
• Fear of being embarrassed

• Mild cases: CBT
• But, many cases require medication.
• SSRIs: ie- Paroxetine [Paxil], Sertraline [Zoloft]
• Beta blockers: ie- Propranolol [Inderal]
• Benzodiazepines: ie- Alprazolam [Xanax]

• Intense, pervasive worry over virtually every aspect of life; (job performance, health, marital relations, social life)
• Difficulty controlling the worry;
• Associated w/ physical manifestations of anxiety.
• Lifetime prevalence is approx. 5%.
• Typical age of onset is early 20s, but may begin at any age.
• Do Not have panic attacks, phobias, obsessions, or compulsions;
• Rather, they experience pervasive anxiety & worry (apprehensive expectation) about a number of events or activities that occur most days x at least 6 mos.
• Plus, at least 3 of the following syx:
• Restlessness, easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, sleep disturbance.

• Relaxation techniques;
• Meds: SSRIs, Buspirone (BuSpar), Benzodiazepines, Beta-blockers

• Persistent re-experience of a trauma, efforts to avoid recollecting the trauma, & hyperarousal.
• Prevalence: 0.5% in Men, 1.2% in Women.
• May occur at any age;
• May begin hours/days/years after the initial trauma.
• People w/ PTSD have endured a traumatic event (combat, physical assault, rape, explosion) in which they experienced, witnessed, or were confronted with actual or potential death, serious physical injury, or a threat to physical integrity.
• Event re-experienced through repetitive intrusive images or dreams, or through recurrent illusions, hallucinations, or flashbacks of the event.
• Pats. make efforts to avoid recollection of event, thru psychological mechanisms or actual avoidance of circumstances that will evoke recall.
• Feelings of detachment from others;
• Exhibit evidence of autonomic hyperarousal (ie- difficulty sleeping, exaggerated startle response).

• Psychotherapy (individual or group)
• Plus meds (directed at specific syx):
• SSRIs x > 6 mos. = most effective for reducing syx;
• TCAs can also be effective;
• **Propranolol & other beta blockers may have a role in preventing development of PTSD if given early after trauma.

• Pats. experience recurrent obsessions & compulsions that cause significant distress and occupy a significant portion of their lives.
• Lifetime prevalence: 2% to 3%.
• Typical onset between late teens and early 20s; but, one third show syx of OCD before age 15
• Seen more frequently after brain injury or disease (head trauma, seizure d/o’s, Huntington’s disease).
• Monozygotic twins have higher concordance rate than dizygotic twins.

• Obsessions: recurrent intrusive ideas, thoughts, or images that cause significant anxiety & distress.
• Compulsions: repetitive purposeful physical or mental actions that are generally performed in response to obsessions.
• The compulsive “rituals” are meant to neutralize the obsessions, diminish anxiety, or somehow magically prevent a dreaded event or situation.

• Obsessions are usually unwanted, resisted, & recognized by patients as coming from their own thoughts;
• Delusions are generally regarded as distinct from patients’ thoughts and are typically not resisted.

• CBT (desensitization, et al);
• Plus Meds:
• SSRIs: Paroxetine (Paxil), Fluoxetine (Prozac), Sertraline (Zoloft);
• TCA: Clomipramine (Anafranil)

inability to experience pleasure from activities usually found enjoyable, e.g. exercise, hobbies, music

• (MDD)
• At least 5 of the following symptoms for at least 2 weeks duration and at least one of these symptoms is depressed mood or anhedonia
• -Significant change in weight
• -Sleep disturbance
• -Psychomotor agitation or retardation
• -Fatigue or loss of energy
• -Excessive guilt or feelings of worthlessness
• -Difficulty concentrating
• -Recurrent thoughts of death or suicide
• Must be a change from previous functioning
• Symptoms must cause social/occupational dysfunction or distress
• Cannot be caused by a medical condition, medication or drugs
• Symptoms cannot be caused by bereavement
• Occasionally no subjective depressed mood is present; only anxiety and irritability are displayed
• Hopelessness and helplessness are common
• Decreased libido
• Patients may appear demented because of poor attention, poor concentration, and indecisiveness
• Assess for risk of suicide
• Check for hypothyroid

• Males: 3-5%
• Females: 8-10%
• Doubled from 1992 to 2002
• More common in populations with greater burden of medical illnesses, including residents of assisted living/nursing homes, recipients of home health care, and patients suffering from medical conditions
• Two times more common in first degree relatives compared to the general population

• First onset may occur at any point from childhood to old age
• Most episodes remit completely, either spontaneously or with treatment (episodes last from several months to a year)
• Persistent major depression (lasting 2 or more years) occurs in 20% of patients
• Highly recurrent, with up to 90% of patients suffering a second episode, with the greatest risk in the first few months and years following remission
• Second only to cardiovascular disorders as the leading cause of functional disability (day-to-day functioning)
• Impacts the outcomes of comorbid medical conditions as well as increases the risk of strokes, diabetes, CAD

more than 12 months of grieving a loss

• Differential Dx of Major Depressive Disorder
• Normal bereavement
• Adjustment disorder with depressed mood
• Dysthymia
• Bipolar Disorder
• Anxiety Disorder
• Schizophrenia and Schizoaffective disorder
• Dementia
• Mood disorder due to a general medical condition
• substance induced mood disorder

• Same symptoms, lasting <1 year, but functioning (i.e. go to work, take care of self/children)
• Symptoms should not cause severe functional impairment lasting more than 2 months
• Treatment: Supportive psychotherapy

• Change in mood and or behavior, which occur within 3 months of a stressor (i.e. break-up) and must not last more than 6 months
• Treatment: Supportive psychotherapy because usually self-limited

• Depressed mood >2 years, but mood does not hit rock bottom
• Dysthymia is a chronic type of depression in which a person's moods are regularly low. However, symptoms are not as severe as with major depression.

• Ask if patient was ever manic (i.e.- patient comes in for help when depressed, not when they are manic)
• Cyclothymia - mild form of bipolar, lasts > 2 years
• Check for hyperthyroid

• Symptoms of anxiety often coexist with depressive symptoms
• Focus on the treatment of depression because it carries a higher morbidity and mortality (i.e.- Antidepressants also treat anxiety)

• Severe psychotic depression may be difficult to distinguish from primary psychotic disorder
• In psychotic depression, generally the mood symptoms usually precede the psychotic symptoms
• In Schizophrenia, there is absence of mood symptoms

• Dementia and depression may present with apathy, poor concentration, and impaired memory
• Differentiation can be difficult in the elderly. A trial of antidepressants may be useful because depression is reversible and dementia is not
• “Pseudodementia” is defined as depression that mimics dementia

Symptoms are a direct physiological consequence of a medical disorder and not an emotional response to a physical illness (i.e.- hypothyroidism)

• Alcohol, sedatives, antihypertensives, and oral contraceptives can cause depressive symptoms
• Withdrawal from sympathomimetics (“Uppers” such as cocaine) or amphetamines can cause a depressive syndrome. Withdrawal from cocaine = depression. WORRY ABOUT SUICIDE WHEN PATIENTS ARE WITHDRAWING FROM COCAINE!

• Antidepressants (SSRIs, TCAs, MAOIs, atypical agents)
• SSRI – safer
• TCA, MAOI – cardiac toxicity, riskier
• Suicide risk goes up because energy returns before mood starts to improve
• Black box warning – medication for depression might cause increased risk of suicide

• Excessive and rapid weight gain in some atypical antipsychotics
• Bupropion (Wellbutrin) - lowers seizure threshold
• Venlafaxine (Effexor) - can cause HTN
• Trazodone (Desyrel) - priapism and hypotension (inhibition of alpha-1 receptors)

• orthostatic hypotension
• hypertensive crisis (tyramine in diet)
• drug interactions with epinephrine, meperidine (demerol), and SSRIs can be life-threatening

dry mouth, blurry vision, constipation

• GI symptoms
• Teratogenic (pregnancy test prn; pt. using bc?)
• Nephrotoxic (check renal functions)
• Conduction defect (check EKG/get a baseline)
• Tremors
• Hypothyroidism (check TFTs)
• Thirst, acne, weight gain, leukocytosis (usually benign), diabetes insipidus

• Bed wetting
• Use TCA (Imipramine (Tofranil)) to treat children

frequent urination

• Bipolar:
• psychotic
• delusions of grandiosity
• expansive or labile mood when manic
• depressed mood when depressed
• Schizophrenia:
• psychotic
• bizarre delusions
• absence of mood symptoms

characterized by rapidly shifting or changing emotions, as in bipolar disorder and certain types of schizophrenia; emotionally unstable

• (dysthymia)
• Depressed mood most of the day, more days than not, for at least 2 years, mood does not hit rock bottom
• Presence of at least two depressive symptoms
• Over a 2 year period, the patient has not been without symptoms for more than 2 months consecutively
• No major depressive episode has occurred during the first two years of the disturbance
• Symptoms do not occur with a chronic psychotic disorder
• Symptoms cause significant social or occupational dysfunction or marked subjective distress
• R/O substance abuse and GMC (general medical condition)

• Symptoms are similar to major depression. Common symptoms are anhedonia, feelings of inadequacy, social withdrawal, guilt, irritability, decreased productivity
• Changes in sleep, appetite, or psychomotor behavior are less common
• Patients often complain of multiple physical problems, which may interfere with social or occupational functioning
• Psychotic symptoms are not present
• Episodes of major depression may occur after the first two years of the disorder, known as "double depression"
• Lifetime prevalence = 6%
• Onset: childhood or adolescent
• Dysthymia occurring prior to the onset of major depression has a worse prognosis than major depression without dysthymia

• Major depressive disorder
• substance induced mood disorder
• mood disorder due to general medical condition
• personality disorders

general medical condition

Dysthymia leads to chronic, less severe depressive symptoms.

Alcohol, bezodiazepines, and other sedative-hypnotics can mimic dysthymia symptoms, as can chronic use of cocaine and amphetamines. Anabolic steroids, oral contraceptives, methyldopa [Aldomet], beta-blockers, and isotretinoin [Accutane] have also been linked to depressive symptoms.

• Depressive symptoms consistent with dysthymia may occur in stroke, Parkinson’s, multiple sclerosis, Huntington’s, vitamin B-12 deficiency, hypothyroidism, Cushing’s disease, pancreatic CA, and HIV.
• R/O by history, PE, and labs as indicated.

Frequently co-exist with dysthymic disorder.

Hospitalization is usually not required, unless suicidality is present.

SSRIs are most often used. If SSRIs have failed, a TCA such as desipramine [Norpramin] is often effective.

• Cognitive psychotherapy may help patients deal with incorrect negative attitudes about themselves.
• Insight oriented: Help patients resolve early childhood conflict, which may have precipitated depressive symptoms.
• Combined psychotherapy and pharmacotherapy produces the best outcome.

• Major Depressive Disorder:
• "Hit rock bottom", one or more discrete episodes
• Lifetime prevalence of 3-6%
• Female to Male ratio 2:1
• Onset anywhere from childhood to old age
• Functional impairment
• Can present wit psychotic features
• Dysthymia:
• Chronic, mild form of MDD
• Lifetime prevalence 6%
• Female to Male Ratio 3:1
• Onset in childhood/adolescence
• Usually functional (go on with life)
• No psychosis

Always assess for suicide risk in patients with any mood disorder

act of intentionally causing one's own death

thoughts about or an unusual preoccupation with suicide

refers to the aim, purpose, or goal of the behavior rather than the behavior itself

is a proposed method of carrying out a design that will lead to a potentially self-injurious outcome

self-inflicted, potentially injurious behavior with a nonfatal outcome for which there is evidence (either explicit or implicit) of intent to die. A suicide attempt may result in no injuries, injuries, or death

• 37,000
• (1 million worldwide)

650,000

10th

• 10-40
• 100-200

• Firearm (more men) 57% overall, 62% in men
• Suffocation (hanging)
• Poisoning/overdose (more women)
• Fall
• Cut/pierce

• Firearms (57% overall, 62% in men)
• Hanging
• Poisoning

• psychiatric illness
• prior hx of suicide attempts (5-6x more likely to try again)
• Hopelessness and impulsivity (higher risk than depression)
• Age, sex, race (females 4x more than males, males successful 3x more often)
• Marital status - never married - highest risk, widowed, separated/divorced, married w/o children, married w/ childred - least risk (Basically living alone)
• Occupation - least skilled workers, and then physicians
• Health
• Adverse childhood experiences
• Family Hx and genetics
• Access to firearms
• Sociopolitical, cultural, economic forces

• Social and family support
• being pregnant, having children
• religion
• effective clinical care for any disorders
• access to clinical interventions and support

• In Clinical Practice: the concept of "contracting for safety" or agreeing to a "no harm contract" has been used to imply that patients can promise clinicians that they will try not to harm themselves when they are suicidal.
• Doesn't really work, gives false sense of security

• Columbia - Suicide Severity Rating Scale
• Part of a national and international public health initiative involving the assessment of suicidality

attempting suicide when no one is likely to find you