Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
22 Cards in this Set
- Front
- Back
What are the three general mechanisms to increase Norepi or 5-HT in the synapse?
|
1. block neuronal reuptake
2. block intraneuronal metabolism by MAO 3. block negative feedback receptors (autoreceptors) located in the neuron |
|
What are the tricyclic antidepressants (TCA)?
|
Desipramine
Imipramine |
|
Desipramine and Imipramine MOA?
|
Decrease REMOVAL of neurotransmitter from the synapse
When NE or 5-HT are released by a neuronal impulse, their concentration in the synapse rises and postsynaptic receptors are stimulated. Stim of these postsynaptic receptors is terminated when the presynaptic (neuronal) transporter pumps the transmitter back into the neuron. Therefore, blockade of the presynaptic NE or 5-HT transporter by drugs such as DESIPRAMINE will increase the synaptic concentration of NE or 5-HT, respectively, because they are not being removed from the synapse. -- DESIPRAMINE selectively blocks the NE uptake -- IMIPRAMINE blocks both NE and 5-HT non-selectively Bind IRREVERSIBLY so their effects last long after they are no loner present. After D/C, can take 10-14 days to resynthesize MAO to pre-drug levels |
|
TCA general pattern of S/E’s?
|
General pattern of side-effects is similar – due to these drugs blocking H1 histamine receptors, muscarinic receptors, and α-adrenergic receptors
MUSCARINIC -- dry mouth, urinary retention, blurred vision, constipation -- memory impairment -- sexual dysfxn HISTAMINERGIC -- sedation -- weight gain α1-ADRENERGIC -- orthostatic hypotension -- sexual dysfxn |
|
TCA cardiovascular effects?
|
1. Tachycardia
2. Changes in cardiac conduction -- in pts w/ normal conduction, change not significant -- most prominent ECG changes are inversion or flattening of the T waves, and increase in the PR interval (due to increase intraventricular conduction time) -- in pts w/ pre-existing cardiac disease, an increased tendency to develop AV block when treated w/ TCA -- can cause severe arrhythmias in overdosage 3. orthostatic hypotension; partially due to α1-adrenergic antagonist activity |
|
TCA CNS effects?
|
1. Fine, rapid tremor of extremities or ataxia—especially in elderly receiving high doses
2. Initiation of manic episodes in “bipolar” patients 3. Lower seizure threshold; can increase risk of tonic-clonic seizures |
|
TCA overdosage?
|
Overdose can be life-threatening. Remember that these drugs are being given to pts w/ high risk of suicide.
-- Deaths reported w/ doses of about 2,000mg -- Severe intoxication w/ doses above 1,000mg Usual daily dose of TCAs range from 75-250mg |
|
What are the MAOI’s?
|
Phenelzine
Tranylcypromine |
|
Phenelzine and Tranylcypromine MOA?
|
Increases RELEASE of neurotransmitter into the synapse
Once NE is taken back into the cytoplasm of the NE neuron by the transporter, it is either: -- destroyed by MAO-A located in the mitochondria, OR -- it is taken up by NE storage vesicles from re-use in neurotransmission In this way, the cytoplasm of the neuron is usually devoid of NE because MAO-A acts like a vacuum cleaner for cytoplasmic NE -- only NE in storage vesicles is protected by MAO and released by a neuronal impulse When patient is treated w/ MAO inhibitor such as PHENYLZINE -- NE taken back up into the cytoplasm by the NE transporter is NOT degraded by MAO-A -- concentration of NE in the cytoplasm rises -- causes concentration of NE in the synapse to increase as the NE transporter, which normally acts to remove NE from the synapse, can work in the “reverse” direction so as to facilitate the movement of NE along its concentration gradient 5-HT is also metabolized by MAO-A, so treatment w/ PHENYLZINE also increases the cytoplasmic concentration of 5-HT by a similar mechanism |
|
MAOI side effects?
|
1. HEPATIC TOXICITY
-- low incidence w/ currently used MAOIs -- very serious when it occurs due to damage to liver parenchyma (mortality rate of 20-25%) -- only w/ PHENELZINE 2. CNS EFFECTS -- generally signs of excessive stimulation -- tremors, insomnia, agitation -- precipitation of hypomanic or manic rxn in bipolar pts 3. CV EFFECTS: orthostatic hypotension due to either -- heightened stimulation of central α2 adrenoceptors OR -- accumulation of false transmitter “octopamine” in peripheral sympathetic neurons 4. FOOD AND DRUG interactions -- “cheese” reaction -- due to ingestion of indirectly acting sympathomimetic amines -- can cause HTNsive crisis -- need dietary restrictions **DO NOT take decongestants with this medicine |
|
What is the alpha2-adrenoceptor blocker?
|
Mirtazapine
|
|
Mirtazapine MOA?
|
Blocks NEGATIVE FEEDBACK mechanism
Negative feedback mechanism can modulate NE or 5-HT release -- NE reaches critical concentration in synapse and stimulates presynaptic alpha2-adrenoceptors (autoreceptors) -- autoreceptors partially inhibit further NE release Autoreceptors are found in terminal areas and cell body areas MIRTAZAPINE blocks this receptor to amplify the amount of NE released for any given frequency of neuronal stimulation There is NO block for the inhibitory presynaptic 5-HT receptors |
|
What is Buproprion’s MOA?
|
Dopamine uptake (?)
|
|
What are the SSRI’s?
|
Sertraline “Some Patients Can Feel Fine Eventually”
Paroxetine Citalopram Fluoxetine Venlafaxine Fluvoxamine Escitalapram |
|
SSRI MOA?
|
Block the reuptake of serotonin
|
|
What is special about Venfaxine?
|
SSRI but also TCA-like
At lower doses, it acts primarily as an SSRI At higher doses, it non-selectively blocks the reuptake of both serotonin and norepi |
|
SSRI and OTHERS side effects?
|
1. None inhibit MAO so no risk of HTN crisis
2. No anticholinergic side effects w/ trazodone, SSRI’s, buproprion, venlafaxine, or mirtazapine nor effects on conduction system of heart 3. No orthostatic hypotension w/ trazadone, bupropion, SSRIs or venlafazine 4. Buproprion has greater tendency to produce seizures than other marketed antidepressants 5. Mirtazapine blocks H1 (and 5-HT2) receptors quite potently. Probably responsible for its considerable weight gain |
|
Most prominent S/E’s of SSRIs and venlafaxine are…?
|
1. nausea and vomiting
2. sexual dysfxn (anorgasmia, ejaculatory disturbance) 3. mechanism: same pharm effect producing efficacy -- enhanced serotonergic transmission at certain serotonin receptors 4. late-developing weight gain |
|
What’s the pharmacology of SSRI-Induced side-effects?
|
Anxiety, insomnia, agitation – 5-HT2
Sexual dysfxn – 5-HT2 Satiation/weight loss – 5-HT2C Nausea/vomiting – 5-HT3 Be able to recognize these symptoms!! |
|
What drug combination will restore sexual fxn?
|
Buproprion + SSRI will restore sexual fxn
|
|
What is the overall efficacy of the different antidepressants?
|
They are all approx equivalent in efficacy w/ about 65-75% of patients responding to an extent that is significant clinically
|
|
Which drugs produce the least serious side effects?
|
SSRIs
Mirtazapine Venlafaxine |