Neuro (pt 4/4) Anti-Depressants & Parkinson's Dz Flashcards
What is Major Depressive Disorder (MDD)?
(unipolar) Often totally disabling, interfering with work, sleep, and eating
What is Dysthymia?
Less severe than major depression and involves long term chronic symptoms that do not disable but keep a person from functioning at their highest level
What is Bipolar Disorder?
(manic depressive disease) Characterized by cycles of severe highs and gut-wrenching lows, often develops into psychotic states
What are discontinuation symptoms of SSRIs, SNRIs, and TCAs?
Dizziness and paresthesias beginning 1-2 days after sudden d/c of the drug
-May persist for 1 wk or longer
What are discontinuation symptoms of MAOIs?
Delerium like state with psychosis, excitement and confusion
What are the general pharmacokinetics of Anti-Depressants?
-PO absorption is rapid (Peak 2-3 hours)
-Tightly bound to plasma proteins (bad for malnourished, low albumin, anorexic patients)
-Hepatic metabolism
-Cleared renally
-Inhibit CYP metabolism (!!!!)…beware of drug-drug interactions when patients are on anti-depressants
What are the therapeutic uses for Anti-Depressants?
-Psychological depression (Major; Dysthymia)
-Anxiety Disorders: PTSD, OCD, General Anxiety Disorder, Panic Disorders, Phobias
-Pain Disorders
-Premenstrual Dysphoric Disorder
-Smoking Cessation
-Eating Disorders
-Bipolar disorder: Lithum +/- anticonvulsant medications
What is Monoamine Oxidase?
Enzyme that breaks down catechols.
Two types:
-MAO-A = present in the NE and Dopamine neurons (Primarily in the brain, gut, placenta, liver)
-MAO-B = present to a greater extent in Serotonin and Histamine neurons
What do you give if patient is hypotensive and takes MAOI?
If hypotensive, need to give a direct acting vasopressor (not one that increases levels of catechols - would cause exaggerated response)
How do Monoamine Oxidase Inhibitors (MAOIs) work?
-Allows for neurotransmitters to accumulate over a period of weeks
-induces down regulation of adrenergic and serotonin receptors
-Currently rarely used due to toxicity and potentially lethal food/drug interactions
-Reserved for tx of depression unresponsive to newer drugs
-Some benefit in Parkinson’s
What are the potentially lethal food interactions with MAOIs?
Tyramine - smoked meats, wine, cheeses
What are the adverse effects of MAOIs?
Orthostatic hypotension
Weight gain
High incidence of sexual dysfunction
Sedation vs. insomnia or restlessness
A first generation anti-depressant
-Tricyclic Antidepressant
-Non selective axon terminal reuptake inhibitor of NE and Serotonin
Imipramine (Tofranil)
What are the adverse effects associated with Imipramine (Tofranil)?
-Increased BP & HR
-Insomnia, anxiety, agitation, sedation
-Anti-cholinergic effects: Dry mouth, constipation, urinary retention, blurry vision, confusion
-Potential for orthostatic hypotension
-Weight gain
-Sexual dysfunction
A selective serotonin reuptake inhibitor (SSRI) (SSRIs are the most common anti-depressant in use)
-Primary action is the inhibition of the serotonin transporter
-Less SE than Tricyclic
Fluoxitine (Prozac)
What are the adverse effects associated with Fluoxitine (Prozac)?
GI upset
Diminished sexual function/disinterest
HA, insomnia or hypersomnia
Most SSRI’s are Category C Drugs (fetal effects in animal studies)
An atypical - heterogenous drug.
-Second/third generation anti-depressants
-Tetracyclic structure
-A pre-synaptic Alpha2 Adrenergic receptor antagonist on NE and serotonin neurons
-Inhibitor of these auto-receptors increases the release of NE and serotonin
-Not associated with sexual side effects
-Not commonly used – reserved for MDD that is unresponsive to other agents
Mirtazapine (Remeron)
An atypical - heterogenous drug.
-Treatment for an acute exacerbation as well as prevention
-Ill defined mechanism
-Sustained lithium exposure stimulates Glutamate reuptake (Reducing the effects of the excitatory transmitter)
-Inhibits second messenger formation (IP3 & DAG) and glycogen synthase kinase-3
-Not metabolized – excreted entirely in the urine
Lithium – for Bipolar Disorder
What are the Adverse Effects associated with Lithium?
Tremor, choreoathetosis, motor hyperactivity, ataxia, dysarthria, aphasia
Hypothyroidism
Polyuria, polydipsia, loss of responsiveness to ADH
Edema
C/I in Sick Sinus Syndrome b/c of SA node depression
Questionable teratogenicity
Overall, toxicity and SEs are the least in which class of anti-depressants?
SSRIs
How is MAOIs effect on BP diet dependent?
MAOIs can cause orthostatic hypotension.
-MAOIs inhibit the catabolism of dietary amines
-Tyramine is found in aged cheese, red wine, and beer
-Tyramine is a catecholamine releasing agent
↑NE = ↑BP ⟹ HTN Crisis
-MAO also metabolizes histamine therefore MAOI’s are also antihistamine antagonists
What are the ANS effects of Lithium toxicity?
Nephrogenic Diabeties Insipidous
(Blocks ADH effects)
What is the cause of Parkinsonism?
Lack of dopamine in the brain
-Muscle rigidity, bradykinesia, tremor, postural instability
-Cognitive declination as the disease advances
-Affective disorders – anxiety or depression
-Personality changes
-Autonomic dysfunction (Sphincter or sexual dysfunction, choking, sweating abnormalities, sensory issues)
-Progressive
-Treatment – essentially D2 stimulation, symptom management only
What is the treatment for Parkinsonism?
-D2 Stimulation
-Symptom management
-Levodopa/Carbidopa
-Dopamine Agonists
-MOAI
-COMT Inhibitors
