Sexual side effects

1

• Sexual side effects
• Appear to result from D2 receptor blockade in
  tuberoinfundibular DA tract
• This cause elevation in Prolactin levels
• Prolactin is elevated following orgasm and is
  bodys signal that causes refractory period

2

• Life Course of SZ
• Chronic illness for 50 to 70 of those given
  initial diagnosis
• Studies uncommon
• Methods
• High risk samples
• High risk relatives more likely to show
  emotional and behavioral problems
• Twin studies Non-SZ twin performs better on
  cognitive tests than Sz but worse than twins in
  pairs where neither develops SZ
• In high risk groups, only 10-15 actually
  develop disorder so samples need to be large.

3

• Methods
• High risk samples
• 2. Birth Cohort Method no particular risk
  factors just large longitudinal samples
• Sz delayed developmental milestones, speech,
  behavioral difficulties lower IQ scores (0.25 to
  0.75 std dev)
• 3. Longitudinal studies during course of illness
• Begin at first episode presented at diagnosis
• May last 5 years
• (or begin at later time points)

4

• Life Course of Adult Onset SZ
• Childhood Premorbid period
• Cognitive, emotional, behavioral, motor evals
  as a group, differences seen
• Mild differences
• II. Adolescence
• Social Withdrawal
• Mood and personality differences
• III. Prodromal Period (months to years prior to
  diagnosis)
• Attenuated psychotic features manageable
  paranoia and delusions
• IV. Florid Psychosis leading to diagnosis
• Time varies with SES, education of parents,
  availability of health care

5
Would it be helpful to treat during earlier
periods? Not likely
6
V. Adulthood Cognitive features remain
consistent (worse during psychotic episodes,
confounds literature re cognitive ability) 15
show worsening of symptoms but data arent
good Positive symptoms recur Negative symptoms
begin or persist VI. Elderly gt65 years Less
than 5 of studeis include subjects over
55. Data are on institutionalized samples only
worse end of symptom spectrum Cognitive decline
seen in 51 over 4 year period no
controls Highest risk in those with most severe
positive and negative symptoms and lower
educational levels

7

• 2 motor control systems
• Pyramidal Motor System voluntary movements
• Extrapyramidal Motor System involuntary motor
  movements, posture, balance, tone. Also provides
  feedback to primary motor system that refines
  movement quality.
• dampens erratic motions, maintains muscle tone
  and truncal stability
• EP side effects largely focus on erratic
  movements and odd postures
• major parts - caudate, putamen, and globus
  pallidus (also known as the Basal Ganglia)
• use Ach, DA, GABA as major controllers
• when DA blocked (D2 receptors), symptoms occur
  focus is on disturbed ratios of neurotransmitters
• Extrapyramidal Symptoms often seen in untreated
  SZ and at first episode
• Vulnerability present drugs challenge system
  further

8
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9
Extrapyramidal side effects Haldol gt
Phenothiazines as class gt Newer meds as class
10

• Extrapyramidal side effects
• Parkinsonism Thorazine shuffle
• difficulty initiating movements, rigidity,
  tremor, handwriting disturbances, postural
  disturbances (may walk backwards at first), head
  rotations
• difficult to turn will into movement
• progresses to stiff shaking or immobility
• locked, frozen hold on patient
• more likely in older patients

11

• Parkinsonism
• Results from dopamine blockade predominating
  over acetylcholine blockade then Ach rules and
  produces the symptoms
• Sometimes treated with antimuscarinic
  (anticholinergic) agents to reduce ACh activity
  and balance it with DA
• Phenothiazines that block DA and ACh equally
  (Mellaril Trilafon) show fewer motor side
  effects
• Other Phenothiazines and Haldol are worse
• Many newer are better than most older

12

• II. Drugs
• Phenothiazines
• c. Side effects
• Extrapyramidal side effects
• Parkinsonism
• Akathisia compulsive restlessness desire to
  move
• (Greek not sitting down)
• Patients describe a jittery feeling in the
  abdomen and weird muscle sensations that are
  relieved by movement.
• Symptoms are sometimes mistaken for anxiety.
• Patients dont like it may discontinue.
• More likely in younger patients

13

• II. Drugs
• Extrapyramidal side effects
• 1. Parkinsonism
• Akathisia
• Dystonias sudden jerky movements sometimes seen
  at initial treatment or when dose is increased
• Neck may arch severely backwards
• Mouth puckers and tongue protrudes
• Difficulty swallowing
• Profuse sweating

14

• II. Drugs
• Extrapyramidal side effects - all treated by
  antiParkinsons drugs efficacy not established
• 1. Parkinsonism
• Akathisia compulsive restlessness desire to
  move
• Dystonias sudden jerky movements sometimes seen
  at initial treatment or when dose is increased
• 4. Akinesia reduced movements muscular
  rigidity may advance to catatonia appear
  depressed limited facial expression
• All above can be fully reversible if meds
  stopped. Some symptoms may persist as part of
  tardive dyskinesia.

15
II. Antipsychotic Drugs Phenothiazines Side
effects Extrapyramidal Parkinsonism (and
akinesia) 20 Dystonia 10 Akathesia
20-25 Tardive Dyskinesia 4/year of
treatment accumulates to 20-50 during chronic
treatment on phenothiazines as class
16

• 5. Tardive dyskinesia movement disorder that
  appears after years of use (can occur after
  months in particularly sensitive people)
  usually irreversible
• Worming motions of tongue on bottom of mouth
• Fluttering eyelids
• Trembling upper lip
• Lip smacking and puckering
• Tongue protrusions (or holding in cheek)
• Puffing and blowing the cheeks
• Head arching or twisting
• Pelvic movements
• Flailing of limbs

17

• 5. Tardive dyskinesia movement disorder that
  appears after years of use (can occur after
  months in particularly sensitive people)
  usually irreversible
• Cause may be depolarization blockade then cell
  death
• When presynaptic autoreceptors are blocked, they
  cannot act to inhibit neurotransmitter release.
  The neuron keeps releasing DA until it cannot
  anymore levels drop and cell dies. Meanwhile,
  postsynaptic neuron builds more D2 receptors,
  producing an abnormally large response to DA.
  Result is motor side effects of TD.
• Antioxidant treatments (such as Vitamin E) can
  help reduce occurrence
• Keep dosages as low as possible for SZ symptom
  reduction and switch to a different phenothiazine
  or new antipsychotic if symptoms occur

18
5. Tardive dyskinesia Risk factors - non-whites
at greater risk - certain genetic polymorphisms
cause higher risks - experience of EPS early in
treatment predict greater risk 50 of all who
develop TD had EPS early on - greater duration
of treatment - age - substance abuse, esp
stimulants - nicotine (smoking) offers some
protection
19

• Diagnostic and Statistical Manual - IVSubstance
  Dependence Disorder
• A maladaptive pattern of substance use leading to
  clinically significant impairment or distress as
  manifested by three (or more) of the following,
  occurring at any time in the same 12-month
  period
• Substance is often taken in larger amounts or
  over longer period than intended
• Persistent desire or unsuccessful efforts to cut
  down or control substance use
• A great deal of time is spent in activities
  necessary to obtain the substance (e.g., visiting
  multiple doctors or driving long distances), use
  the substance (e.g., chain smoking), or recover
  from its effects
• Important social, occupational, or recreational
  activities given up or reduced because of
  substance abuse
• Continued substance use despite knowledge of
  having a persistent or recurrent psychological,
  or physical problem that is caused or exacerbated
  by use of the substance
• Tolerance, as defined by either
• need for increased amounts of the substance in
  order to achieve intoxication or desired effect
  or
• markedly diminished effect with continued use of
  the same amount
• Withdrawal, as manifested by either
• characteristic withdrawal syndrome for the
  substance or
• the same (or closely related) substance is taken
  to relieve or avoid withdrawal symptoms

20

• Glutamate Hypothesis of SZ
• use of Phencyclidine (PCP) - produces similar
  symptoms. Caused by altered Glutamate
  transmission due to antagonistic action at NMDA
  receptor blocks NMDA receptor (hypoglutamate
  idea) but also stimulates D2 receptors
• modest info suggest enlargement of ventricles
  within 2 years of first diagnosis
• Excitotoxicity maturation-dependent period of
  excessive glutamate may be destructive and lead
  to excessive pruning
• free radicals also do damage antioxidants
  helpful re destructive issues

21
2002 Household Survey (NIDA/CDC) 3.3 of adults
require treatment for drug abuse 8 for
alcohol 30 for smoking With mental illness, 23
report substance abuse Without, 8.2 18-25 year
olds 20 report drug use vs 8.2 of adults 94
deny a problem even when using most days of a
month.