What are some functions of serotonergic pathways in the brain?
mood, appetite, sleep, cognition, memory, thermoregulation, nausea
What cells make 90% of the serotonin in the body?
Enterochromaffin cells in GI
What is the effect of serotonin on the GI?
increases GI motility, may cause nausea, gut immune response
What is the function of serotonin stored in platelets?
vasoconstriction, platelet aggregation, clot formation
What conditions are treated with therapies that increase serotonin?
depression, anxiety, insomnia, OCD, migraines,
aggression
What are the symptoms of serotonin syndrome?
Cognitive effects: headache, agitation, hypomania, mental confusion,
hallucinations.
Autonomic effects: hypertension, hyperthermia, shivering, sweating, nausea,
diarrhea
Somatic effects; tremor, hyperreflexia, myoclonus
What is carcinoid syndrome?
Caused by tumors of enterochromaffin cells secreting excess serotonin Symptoms: diarrhea, flushing, dyspnea, abdominal pain
What is the rate-limiting step in serotonin synthesis? What is this most dependent upon?
Tryptophan → 5-HTP
Tryptophan Concentration
Why might giving someone tryptophan result in a decrease in catecholamines?
Dopa decarboxylase is used in serotonin synthesis and catecholamine synthesis. These pathways compete for the same enzyme.
How is 5-HT neurotransmission terminated?
reuptake from synaptic cleft into presynaptic neuron
Why should MAO inhibitors not be given at the same time as selective serotonin uptake inhibitors (SSRIs)?
MAO inhibitors increase serotonin levels and used in conjunction may cause serotonin syndrome
What are some conditions that are treated with 5-HT receptor agonists?
migraines
What are some conditions that are treated with 5-HT receptor antagonists?
nausea and vomiting
What is the main inhibitory neurotransmitter in the CNS?
GABA
What are effects of GABA?
sedative/hypnotic, anti-anxiety, and anti-convulsive effects
How are substances that increase GABA activity used?
seizure disorders, anxiety disorders, and insomnia
How are substances that decrease GABA activity used?
to counteract the effects of
overdose of GABA agonists. Historically, they were used to induce seizures for anti-depressant therpy
What amino acid is the precursor for GABA?
Glutamate
In addition to the binding site for GABA, what other binding sites exist on the GABA receptor?
binding sites for benzodiazepines, barbiturates, and ethanol
Where do many of the nervine herbs bind on the GABAA receptor?
At the benzodiazepine site
What is the main excitatory neurotransmitter in the CNS?
Glutamate
What is the excitotoxicity theory?
prolonged or repeated depolarization of a neuron due to stimulation by glutamate (or other excitatory NT) leads to cell damage and death
What is the immediate precursor for glutamate in the brain?
Glutamine
How is glutamate neurotransmission terminated?
taken back up into neurons and astrocytes
What are some endogenous opioids?
endorphins, enkephalins,
and dynorphins
What are endogenous opioids involved in?
“Runner’s high”, pain suppression, reward, mood, motor coordination,
feeding, body temperature, immune response, and response to stress
What are effects of opioid overdose?
cardiovascular and
respiratory depression, nausea, vomiting, constipation and pupillary constriction
What is the relationship between beta-endorphin and ACTH? How is this important in the stress response?
They come from the same propeptide (pro-opiomelanocortin POMC). In the stress response, when CRF stimulates ACTH production, β-endorphin is also
produced
From what molecule are endogenous cannabinoids derived?
arachidonic acid
What are functions of endogenous cannabinoids?
analgesia, eating behavior, immune function, mood,
sleep and memory
Why are endogenous cannabinoids not stored in membrane vesicles?
Because they are lipid soluble
How is obesity defined?
BMI > 30kg/m2.
What BMI is associated with the lowest point of all-cause mortality?
23-24 kg/m2
What health condition is responsible for most of the increased mortality with obesity?
CHD
What other health conditions are associated with obesity?
All the things.
What waist circumference in men is associated with increased risk of cardiovascular disease? In women?
Men > 40in
Women >35in
What factors determine what a healthy weight is for a particular patient?
clinical picture, diet and exercise history, laboratory biomarkers, and family history.
What are some causes of obesity?
Genetics, microbiome, physical activity, diet, environmental toxins, stress, sleep-disorders
What are some things to consider in the medical interview when discussing weight loss with a patient?
motivation to lose weight, hx of eating d/o, ROS, medications, sleep d/o, stress level, gut health, family hx, diet, physical activity, weight hx, dieting hx, readiness for change
What are some effects of weight cycling?
o Increased total body fat and central adiposity
o Increased food efficiency
o Decreased energy expenditure
Increased BP, insulin resistance, and blood lipids
What are some things to consider when coming up with a treatment plan for obesity?
individualization
Treatment goals such as wt. loss goal, reducing bp, glucose, etc., treating GERD, improving mood
What is necessary for a diagnosis of: Anorexia nervosa (AN)
Persistent restriction of energy intake leading to
significantly low body weight
• Either an intense fear of gaining weight or of becoming
fat, or persistent behavior that interferes with weight
gain (even though significantly low weight).
• Disturbance in the way one’s body weight or shape is
experienced, undue influence of body shape and weight
on self-evaluation, or persistent lack of recognition of the
seriousness of the current low body weight.
What is necessary for a diagnosis of: Bulimia nervosa (BN)
• Recurrent episodes of binge eating, which are
characterized by:
– Eating excessive amounts rapidly usually as a hidden, possibly
planned, behavior
– Lack of control
• Recurrent compensatory behavior to prevent weight
gain: vomiting, laxatives, diuretics, other medications,
fasting, or excessive exercise.
• Behaviours occur at least once a week for three months.
• Self-evaluation is unduly influenced by body shape and
weight.
• The disturbance does not occur exclusively during
episodes of Anorexia Nervosa.
What is necessary for a diagnosis of:
Binge eating disorder (BED)
Recurrent episodes of binge eating ( > weekly for 3 months)
• The binge eating episodes are associated with >/= 3:
– eating much more rapidly than normal
– eating until feeling uncomfortably full
– eating large amounts of food when not feeling physically hungry
– eating alone because embarrassed by how much one is eating
– feeling disgusted with oneself, depressed or guilty afterward
• Marked distress regarding binge eating is present
• Binge eating not associated with BN or AN
What are physical effects of Anorexia nervosa (AN)
Poor circulation, dry or chapped lips, glossitis brittle fingernails, lanugo, amenorrhea, low libido, abdominal pain, constipation, edema, kidney damage
What are physical effects of Bulimia nervosa (BN)
Chronic sore throat Heartburn and reflux Abdominal pain and bloating Dysregulated bowel patterns: constipation, diarrhea Erosion of dental enamel from vomiting, tooth decay Mental: mood swings, selfharm, anxiety, depression
What are physical effects of
Binge eating disorder (BED)
- Weight gain, often leading to obesity
- High blood pressure
- High cholesterol
- Diabetes
- Stroke
- Gallbladder disease
- Heart disease
- Osteoarthritis
- Irregular menstrual cycle
- Certain types of cancer
- Chronic kidney problems or kidney failure
- Skin disorders – acne, candida, eczema
What is avoidant/restrictive food intake disorder (ARFID)? What are some examples of ARFID?
Basically malnutrition from difficulty eating.
Pts with IBD, interstitial cystitis, picky eaters, people with allergies, anxiety d/o, autism
What are some common psychiatric issues associated with eating disorders?
Depression, anxiety, bipolar, addiction, OCD, PTSD, borderline personality d/o, intentional self-harm, schizophrenia
When should you consider screening for an eating disorder?
• Patients who want a restrictive diet or have restrictive
dieting history
• Patients who have OCD and perfectionist behaviors
surrounding food or diets you give them
• Weight loss or gain in someone with other mood
disorder or recent trauma
• Incidental finding of poor oral health and beat up
knuckles, frequent pharyngitis (purging)
• Observation of cutting behaviors or scars
• Other issues of alcoholism or addiction
• Patients overly preoccupied with their weight
• Children with weight loss or food restrictive behaviors
If a patient has an eating disorder as the primary complaint, what other professionals should be involved in his or her care?
dietician, therapist, psychiatrist, eating d/o program, support groups
When is inpatient hospitalization indicated with an eating disorder? What are some other possible levels of care?
– Unstable or depressed vital signs
– Laboratory findings presenting acute health risk
– Complications due to coexisting medical problems such as
diabetes, particularly type 1 diabetes
– Rapidly worsening symptoms
– Suicidal and unable to contract for safety
Residential treatment, partial hospitalization, intensive outpatient
Why is it important to know whether a patient has a history of an eating disorder? In these patients, what are some things you should not consider doing until you know them well?
They may have a condition that require dietary changes/restriction and these pts may not be good candidates for such diets dt the potential for relapse.
Avoid food sensitivity testing, elimination diets, other highly restrictive diets
Why should drugs and herbs be used in small doses in patients with eating disorders?
low weight, low protein
(more drug unbound), and possibly altered
metabolism associated with starvation and
dehydration
What is the standard treatment for AN?
nutritional rehabilitation
and psychotherapy, which are supported by far more
evidence than pharmacotherapy.
What are some treatments for bone loss with AN?
Supplement vitamin d, ca, mg, HCl, low dose e/p
What drugs are useful in BN?
SSRIs, NO bupropion
What antidepressant should not be used with AN or BN?
Bupropion
What is the first line treatment for BED?
cognitive behavioral therapy
Why is it important not to let patients with AN see their weight?
People with AN may become suicidal when their
weight increases and they find out.
What types of exercise are especially helpful for patients with eating disorders?
yoga, tai chi, qi gong, breathing exercise, fun
What are some possible digestive issues in patients with eating disorders?
maldigestion d/t stress, dysbiosis
What are some counseling techniques that might be useful with eating disorder patients?
EFT, EMDR, CBT