Stimulants:

• Cocaine
• Methylphenidate (Ritalin)
• Bupropion

Cocaine and methylphenidate (Ritalin):

1. block reuptake of Nepi, 5HT and dopamine

2. antidepressants vs. stimulants: most antidepressants do not block the reuptake of dopamine

Bupropion (Wellbutrin) and MAOIs:

1. Bupropion is the only antidepressant that blocks dopamine reuptake.

2. MAOIs enhance the effects of dopamine by blocking its metabolism

3. dopamine receptor stimulation is linked to addictive behaviors. This is why bupropion and MAOIs can be used to treat nicotine addiction.

• block Nepi and 5HT reuptake
• differ from other reuptake blockers b/c they block muscarinic, alpha-adrenergic and histaminic receptors (there is a difference between blocking reuptake and blocking the receptor)
• TCAs are associated with: dry mouth, sedation, tachycardia, and other important side effects
• TCAs are associated with seizures
• TCAs can be very toxic

• block Nepi and 5HT reuptake
• low toxicity

• block 5HT reuptake
• low toxicity
• Prozac

• Think of these as bupropion and all others
• bupropion blocks dopamine (unusual for these drugs) and maybe Nepi
• Bupropion and TCAs lower seizure threshold
• All other atypicals block 5HT reuptake and have +/- effects on Nepi reuptake

• MAO-A block metabolism (and enhance effects of) Nepi, 5HT and dopamine
• MAO-B blocks dopamine metabolism (selegiline)
• MAOIs may be very toxic
• MAOI type B is safer than type A

• Inhibit reuptake
• inhibit metabolism
• increase production (synthesis)

1. What is the biogenic amine theory of depression?

2. How many down regulation of presynaptic inhibitory receptors affect biogenic synthesis and release?

1. Biogenic theory of depression proposes that depression is due to a deficiency of monoamines (Nepi/5HT) at certain key sites in the brain
2. This down regulation will increase synthesis --> increased availability post synapse.

1. What are the pharmacologic similarities and differences between TCAs adn SSRIs?

2. Include the indications and adverse effects in your discussion.

Similarities:

• both block 5HT reuptake

Differences:

• TCAs block Nepi reuptake
• TCAs block muscarinic, histaminic and alpha receptors (note the difference between blocking the reuptake and blocking the receptors)
  
• TCAs are much more toxic than SSRIs

1. Name two serotonin/Nepi reuptake inhibitors (SNRIs) (provide generic and trade names).

2. When might these medications be indicated instead of SSRIs or TCAs.

1. Cymbalta (duloxetine)
2. Effexor XR (venlafaxine)

SNRIs can be effective in relieving physical symptoms of pain (neuropathic)

1. What are the trade names of the atypical antidepressants bupropion, mirtazapine, nefazodone and trazodone?

2. What is known about their mechanism of action?

3. When might these agents be preferred over TCAs, SSRIs, SNRIs?

Bupropion (Wellbutrin): dopamine and Nepi reuptake inhibitor, considered to be low risk for drug-drug interactions.

• This is the only drug that blocks dopamine reuptake
• Can be used for addictive behaviors such as smoking cessation.

• block Nepi/5HT reuptake (and also have many other effects that separate them from SNRIs) increasing monoamines in synaptic cleft --> antidepressant effects
• block alpha adrenergic, histaminic and muscarinic receptors
• TCAs are named b/c of their chemical structure (tricyclic compounds)
• SNRIs are named b/c of their action (block 5HT and Nepi reuptake)
• SNRIs are much less toxic than TCAs

1. What two MAOIs are currently available in the US?

2. Name a muscle relaxant, narcotic and inhalational anesthetic agent that should never be used with MAOIs.

3. What other medications commonly administered during the intraoperative period should be used cautiously in patients taking MAOIs?

1. Halothane and Meperedine (demerol) are contraindicated.

2. Anticholinergic drugs and those with anticholinergic effect should also be avoided if possible

• atropine, glycopyrrolate and pancuronium (muscle relaxant)

3. Avoid indirect acting sympathomimetics b/c of unpredictable or exaggerated effects (ephedrine)

4. Do use direct acting catecholamines and other vasoactive drugs but start with small doses and use with caution.

1. MAOIs inhibit activity of the enzyme monoamine oxidase

2. MAO functions as a safety valve to inactive any excess neurotransmitter (Nepi, dopamine, 5HT)

3. This then prevents the breakdown of monoamine neurotransmitters and increases their availability within the presynaptic neuron

4. MAOIs can either bind permanently or irreversibly to MAO, if bound irreversibly it will take a minimum of 2 weeks for the body to replace these enzymes

5. Anesthesia considerations should be taken if patient is on MAOIs expecially if sympathomimetics are to be used as well as narcotics (demerol), barbiturates and anticholinergics

6. If needed direct acting sympathomimetics should be used as opposed to indirect acting

7. Do not administer MAOIs with SSRIs d/t risk of serotonin-syndrome which can be life threatening

1. What are the indications and mechanism of action of lithium?

2. Which second messenger system is associated with lithium?

3. What special problems are associated with the perioperative management of patients who have been taking lithium?

1. Lithium is an antimanic agent used in the treatment of mani-depressive patients with manic episodes.

2. Lithium is believed to attenuate signaling via receptors coupled to the PIP2 second-messenger system.

3. Patients taking lithium need to have adequate fluid perioperatively to avoid hemoconcentration and resultant toxicity d/t to lithium's narrow therapeutic range.

4. Lithium may potentiate effects of NDMRs. Lithium may affect renal, thyroid, and parathyroid function.

Question 12.1 from book:

A 55 year old teacher began to experience changes in mood. He was losing interest in his work and lacked the desire to play his daily tennis match. He was preoccupied with feelings of guilt, worthlessness and hopelessness. In addition to the psychiatric symptoms, the patient c/o muscle aches throughout his body. Physical and lab tests were unremarkable. After 6 weeks of therapy with fluoxetine, the patient's symptoms resolved. However, the patient c/o sexual dysfunction. Which of the following drugs might be useful?

MIRTAZAPINE

Sexual dysfunction commonly occurs with TCAs, SSRIs and SNRIs. Mirtazapine is largely free from sexual side effects.

Question 12.2 from book:

A 25 year old woman has a long history of depressive symptoms accompanied by body aches. Physical and lab tests are unremarkable. Which of the following drugs might be useful in this patient?

DULOXETINE

Duloxetine is an SNRI that can be used for depression accompanied by neuropathic pain. MAOs and SSRIs have little activity against neuropathic pain.

Question 12.3 from book:

A 51 year old woman with symptoms of major depression also has narrow angle glaucoma. Which of the following antidepressants should be avoided?

AMITRIPTYLINE

Because of its potent antimuscarinic acitivty, amitriptyline should not be given to patients with glaucoma because of the risk of acute increases in IOP.

Question 12.4 from book:

A 36 year old man presents with symptoms of compulsive behavior. If anything is out of order, he feels that "work will not be accomplished effectively or effficiently." He realizes that his behavior is interfering with his ability to accomplish his daily tasks but cannot seem to stop himself. Which of the following drugs would be most helpful?

FLUVOXAMINE

SSRIs are particularly effective in treating obsessive compulsive disorder