Exam 3 - Antidepressants, Drugs of Abuse

Mania

periods of enthusiasm, anger, rapid thoughts, rapid speech, extreme self-confidence, and impaired judgement.

Norepinephrine and serotonin

most antidepressants potentiate the actions of these two biogenic amine neurotransmitters

Selective Serotonin Reuptake Inhibitors (SSRIs)

group of antidepressant drugs that inhibit serotonin reuptake selectively and thereby increase serotonin activity at the synapse. Have little blocking activity against muscarinic, alpha adrenergic, and histaminic receptors. Take up to 2 weeks to produce significant improvement in mood. Maximum benefit can take up to 12 weeks to develop. Ie) fluoxetine, paroxetine

Serotonin Norepinephrine reuptake inhibitors (SNRIs)

group of antidepressant drugs that inhibit the reuptake of both serotonin and norepinephrine. Can also be effective in relieving pain due to dual inhibition. Have little blocking activity against alpha adrenergic, muscarinic, and histaminic receptors. Abrupt termination in treatment can cause a withdrawal syndrome. Ie) venlafaxine, desvenlafaxine, duloxetine

Atypical antidepressants

a mixed group of antidepressant agents that have actions at several different sites. Ie) bupropion

Tricyclic antidepressants

group of antidepressant drugs that potent inhibitors of norepinephrine and serotonin reuptake. Unlike SNRIs these drugs also block serotonergic, alpha adrenergic, histaminic, and muscarinic receptors. While they are more potent than SNRIs they have more side effects due to this reason. Mood elevation takes about 2 weeks or longer. Abrupt termination in treatment can cause a withdrawal syndrome. Ie) imipramine, amitriptyline, desipramine, amoxapine, doxepin

Monoamine oxidase inhibitors

a group of antidepressant drugs that irreversibly or reversibly inactive MAO enzyme. This allows for neurotransmitters such as norepinephrine, dopamine, and serotonin to escape degradation. Ie) phenelzine, isocarboxazid, selegiline

Monoamine oxidase

a mitochondrial enzyme found in nerve and other tissues such as the gut and liver. Functions to oxidatively deaminate and inactive monoamine neurotransmitters like norepinephrine, dopamine, and serotonin that may leak out of synaptic vesicles when the neuron is at rest. A target for antidepressant drugs.

Tyramine

natural compound found in foods such as aged cheeses, meat, and red wine that is not degradable when taken with MAO inhibitors. This compound in excess causing the release of large amount of stored catecholamines from nerve terminals resulting in hypertensive crisis.

Serotonin dopamine antagonists (SDAs)

a group of antidepressants that are occasionally used as adjunctive treatment to antidepressants in partial responders. Ie) aripiprazole, olanzapine

Inositol monophosphatase (IMPase)

enzyme that functions in the normal recycling of membrane phosphoinositides. Blocking of this enzyme by lithium blocks the depletion of free inositol and PIP2, the membrane precursor of IP3 and DAG.

Carbamazepine, valproic acid, lamotrigine

three anticonvulsants that are approved as mood stabilizer in bipolar disorder.

Hallucinogenic drugs (psychotomimetic, psychedelic drugs)

drugs that affect thought, perception, and mood. Mainly cause sensory distortion and hallucinatory experiences. Do not cause dependence. Psychological effects overlap with highly addictive major psychostimulants such as cocaine and amphetamines.

Tetrahydrocannabinol (THC)

the psychoactive alkaloid contained in marijuana

Cannabinoid (CB) Receptors

receptors in the brain that respond to THC found in marijuana. When these receptors are activated, there is a feeling of physical relaxation, hyperphagia, increased heart rate, decreased muscle coordination, conjunctivitis, and minor pain control.

5HT2A

receptor inhibited by LSD. It couples to Gq proteins and generates IP3 leading to the release of intracellular calcium.

fluoxetine (Prozac, longer half life)

paroxetine

Name two SSRIs

venlafaxine

desvenlafaxine

duloxetine

Name three SNRIs

high blood pressure and increased heart rate

What side effect may the patient experience when taking high doses of venlafaxine?

Pain syndromes

(diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, low back pain)

In addition to depression, what is an additional clinical use of SNRIs?

Bupropion

An atypical antidepressant having weak dopamine and norepinephrine reuptake inhibition. Used in the treatment of depression, as well as decreasing withdrawal symptoms and cravings for nicotine in patients attempting to quit smoking.

seizure patients (increased risk of seizures)

patients with eating disorders (decreased appetite)

What two patients should not take bupropion?

increased risk of seizures

What is one major side effect of bupropion?

Imipramine (Tofranil)

Desipramine

Doxepin

Amitriptyline (Elavil)

Amoxapine

Name five tricyclic antidepressants.

blurred vision and withdrawal

what are two important side effects of tricyclic antidepressants?

benign prostatic hyperplasia

epilepsy

arrhythmias

what three medical conditions do tricyclic antidepressants exacerbate?

low therapeutic index

why are tricyclic antidepressants dangerous?

first pass metabolism by the liver

why do tricyclic antidepressants have low and inconsistent bioavailability?

imipramine

which tricyclic antidepressant can be used for bed wetting children?

amitripyline

which tricyclic antidepressant can be used for migraines and neuropathic pain?

doxepin

which tricyclic antidepressant can be used to treat insomnia?

Selegiline

Isocarboxazid

Phenelzine (Nardil, irreversible)

name three MAO inhibitors used in the treatment of depression

phenelzine

which MAO inhibitor is irreversible?

selegiline

which MAO inhibitor is available as a transdermal patch?

hypertensive crisis

when MAO inhibitors are taken with aged foods such as wine and cheese, buildup of tyramine causes this dangerous side effect

SSRIs

which antidepressants should not be take with MAO inhibitors due to serotonin syndrome?

selegiline

which MAO inhibitor can be used in the treatment of parkinson's disease?

olanzapine

aripiprazole

name two SDAs used in the treatment of depression. Commonly taken in junction with other antidepressants.

olanzapine and fluoxetine

which SDA and SSRI are combined for the treatment of major depressive disorder and bipolar depression?

lithium

drug that inhibits IMPase. Used in the treatment of bipolar disorder

low therapeutic index

which is lithium dangerous?

chlorpromazine (thorazine)

haloperidol

two older antipsychotics used in the improvement of manic symptoms

risperidone

olanzapine

aripiprazole

three atypical antipsychotics used to manage mania

MDMA (methylenedioxymethamphetamine, ectasy, molly)

drug of abuse that causes the release of serotonin and blocks its reuptake. Build up of serotonin and depletion of its stores results in euphoria.

benzodiazepines

what class of drugs are used to calm patients who have taken MDMA?

neuromuscular blockers

what class of drugs are used to treat life threatening hyperthermia in patients who have taken MDMA?

marijuana

drug of abuse whose active component, THC, binds to CB1 receptors resulting in euphoria and relaxation. Side effects occur in 20 min and subside after 3 hours.

decreased muscle coordination

conjunctivitis

what are two side effects of marijuana?

reduces short term memory and mental activity

what effect does marijuana have on cognition?

synthetic cannabinoids (spice, K2)

drugs that are sprayed onto marijuana plants in a process known as dusting and are smoked to produce intoxication. Patient will not test positive for THC upon regular drug testing.

convulsions

acute kidney injury

death

what are three major side effects of synthetic cannabinoids?

LSD (lysergic acid diethylamine)

drug that binds to 5HT2A receptors resulting in hallucinations and delusions as well as impaired judgment. Effects appear after 30 min and last about 6-12 hrs.

can induce abortion (due to uterine contractions)

why shouldn't LSD be taken during pregnancy?

ketamine

phencyclidine

two drugs that are antagonists of NMDA type glutamate receptors. Cause hallucinations and visual alterations. Effects last for 1 hour

LSD and phencyclidine

which two drugs of abuse should not be combined due to the risk of schizophrenic attacks?