Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Chapter 3 λ Drugs Used for Depression, Bipolar Disorders, and Attention Deficit Hyperactivity Disorder (ADHD)

λSide effects:

−Narrow therapeutic index; requires therapeutic monitoring

−Tremor, flu-like symptoms, life-threatening seizures

−Hypothyroidism with goiter (↓ TSH effects and inhibition of 5′-deiodinase)

−Nephrogenic diabetes insipidus (↓ ADH effect); manage with amiloride

λTeratogenicity: Ebstein’s anomaly (malformed tricuspid valve)

λOther drugs used in bipolar disorders: valproic acid, carbamazepine

DRUGS USED IN ADHD

λMethylphenidate: amphetamine-like

−Side effects: agitation, restlessness, insomnia, cardiovascular toxicity

λAtomoxetine: selective NE reuptake inhibitor

−Side effects: See TCA section, above.

Chapter Summary

λThe amine hypothesis of depression postulates that symptoms are caused by a functional deficiency of CNS NE and/or 5HT. This is based on the observation that most antidepressants affect the metabolism of these amines. Again, there are exceptions.

λThe uses, drug interactions, and adverse effects of the monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, and other antidepressants are discussed.

λLithium, the mainstay for bipolar disorder treatment, often needs supplementation with antidepressant and/or sedative drugs. The uses, mechanisms of action, and adverse effects of lithium therapy as well as backup drugs used for treatment of bipolar disorder are considered.

λAtomoxetine and methylphenydate are used in the treatment of ADHD.

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Learning Objectives

Answer questions about dopaminergic neural pathways

Demonstrate understanding of dopamine receptors

Compare and contrast the mechanism of action and side-effects for drugs used in Parkinson disease with antipsychotic drugs

DOPAMINERGIC NEURAL PATHWAYS

In the CNS, dopamine (DA) is a precursor to NE in diffuse noradrenergic pathways and is an inhibitory neurotransmitter in the following major dopaminergic pathways:

λNigrostriatal tract

–Cell bodies in the substantia nigra project to the striatum, where they

release DA, which inhibits GABA-ergic neurons. In Parkinson disease, the loss of DA neurons in this tract leads to excessive ACh activity → extrapyramidal dysfunction.

–DA receptor antagonists → pseudo-Parkinsonism (reversible).

–DA agonists may cause dyskinesias.

λMesolimbic-mesocortical tracts cell bodies in midbrain project to cerebrocortical and limbic structures.

–Functions include regulation of affect, reinforcement, cognitive func-

tions, and sensory perception. Psychotic disorders and addiction are partly explained by ↑ DA in these pathways.

–Drugs that ↑ DA functions → ↑ reinforcement and, at high doses, may cause psychoses.

–DA antagonists → ↓ cognitive function.

λTuberoinfundibular

–Cell bodies in hypothalamus project to anterior pituitary and release DA → ↓ prolactin.

–DA agonists are used in hyperprolactinemic states.

–DA antagonists may cause endocrine dysfunction, including gynecomastia and amenorrhea/galactorrhea.

λChemoreceptor trigger zone

–Activation of DA receptors → ↑ emesis.

–DA agonists (e.g., apomorphine) are emetic, and DA antagonists are antiemetic.

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