Pharmacology Exam 4

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mental state of excessive sadness characterized by persistently low mood or extensive loss of pleasure and interest

Major depressive disorder
Tricyclic antidepressants
- three ring core
- similar to phenothiazines
- most NE reuptake inhibitors
Tertiary amines
- inhibit both NE and 5HT reuptake
- imipramine: also anticholinergic
- amitriptyline
- trimipramine: no inhibition at monoamine transport
- clomipramine: most potent; also used for OCD
- doxepin
Secondary amines
- relatively selective NE reuptake inhibitors
- desipramine: less anti ach effect
- nortriptyline: not selective
- protriptyline
Pharmacological action of tricyclic antidepressants in non-depressed pt

no mood elevating effects
action of tricyclic antidepressants in depressed patients
- elevate mood
- decrease time in REM sleep
Anticholinergic actions of TCAs

3` greater than 2`
TCA alpha adrenergic blockade

selective fore alpha 1 more than alpha 2, no affinity for beta
Mechanism of action for TCAs

inhibit neuronal uptake of biogenic amines in the CNS (NE and 5HT)
Pharmacokinetic properties of TCAs
- high protein binding
- highly lipophilic
- well absorbed
- significant 1st pass metabolism
Side effects of TCAs
- anti ACH and alpha adrenergic blockade are common: GI & postural hypotension
- weight gain
- excessive sweating
CNS side effects of TCAs
- hypomania to mania transition
- restlessness
- insomnia
- tremor/seizures
- antihistamine effects
Cardiac toxicity of TCAs
- tachycardia
- orthostatic hypotension
Drug interactions with TCAs

compete with antiepileptics, antipsychotics, smoking and barbituates
Interaction of TCAs with antipsychotics

prodtein binding and additive anticholinergic action
interactions of TCAs with anihypertensive agents

guanethidine
interactions of TCAs with MAOIs
- serotonin syndrome when co-treated with SSRIs
- akathisia like restlessness
Therapeutic uses of TCAs
- used toether with lithium for BPD
- enuresis in children and elderly
- ADHD (NE selective)
- Tourette's
- Severe anxiety disorders
- chronic pain
commonly used SSRT Drugs
- fluoxetine
- paroxetine
- sertraline
- citalopram
- fluvoxamine
pharmacodynamic action of SSRIs

high affinity for serotonin transporter 80% inhibition but not histamine, ach and alpha-adrenoceptors
Pharmacokinetics of SSRIs
- highly lipophilic
- active metabolite is norfluoxetine
potent inhibitors of CYP2D6 and TCA

fluoxetine and paroxetine
Side effects and toxicity of SSRIs
- GI upset
- weight gain
- sexual function
Drug interactions with SSRIS

causes 5-HT syndrome with MAOIs
Therapeutic uses of SSRIs
- MDD
- GAD
- PTSD
- OCT
- Panic disorder
- PMDD & bulimia
SNRIs

venlafaxin and duloxetine
Drug interactions with SNRIs

MAOI causes 5HT syndrome
Therapeutic uses of SNRIs
- panic disorder
- social anxiety disorder
- pain disorder
- urinary incontinence
may be used for diabetic neuropathy and fibromyalgia

duloxetine
5HT2 antagonists
- trazodone
- nefazodone (hepatotoxicity)
Atypical antidepressants

bupropion mirtazapine
bupropion
- unicyclic
- blocks NE and DA reuptake
- increased availability of NE and DA
- smoking cessation
Mirtazapine
- tetracyclic
- presynaptic A2 autoreceptor antagonist
- blocks 5HT2 and 5HT3 receptors
- H1 antagonist
Non-selective & irreversible MAOIs
- phenelzine
- Tranylcypromine
Selective MAOIs
- selegiline (MAO-B)
- Clorgyline (MAO-A)
Pharmacologic actions of MAOIs
- Mood elevation in depressed patient
- increased motor activity and appetite
- excitement and euphoria
- Suppression of REM sleep
Mechanisms of action of MAOIs
- inhibit oxidative deamination of monoamines (NE and 5HT)
- Tranylcypromine: amphetamine like effects
Pharmacokinetic properties of MAOIs
- readily absorbed
- not given parenterally
- Hydrazide: cleaved to hydrazine then acylated
Side effects and toxicity of MAOIs
- excessive CNS stimulation
- orthostatic hypotension
- weight gain
- anorgasmia
- hepatotoxicity (especially with hydrazides)
Drug and Food interactions with MAOIs
- enhance effects of CNS depressants by interfering with metabolism
- potentiate effects of sympathomimetics (hypertensive crisis)
- Tyramine may lead to hypertensive crisis
- first pass metabolism in GI tract and tyramine
Therapeutic uses of MAOIs
- secondary use for depression
- phobic anxiety when TCA and ECT don't work
uses for lithium carbonate
- BPD (especially manic phase)
- prevention of mania and depression
- recurrent endogenous depression
- schizophrenia
- unipolar depression
Mechanism of lithium
- inhibiting sodium dependent action potentials and sodium exchange across the membrane
- inhibition of IP3 and DAG production in neurons, GSK3 inhibition
- Decreases NE and DA turnover
- increases 5 HT activity amd ACH synthesis
- blocks DA receptor supersensitivity
Pharmacokinetics of lithium
- readily absorbed
- eliminated through urine
- increased sodium = increased lithium excretion
- low therapeutic index, requires monitoring
Toxicity with lithium
- acute intoxication
- tremor (propranolol and atenolol may be used)
- prolonged effects
- edema & sodium retention
Prolonged effects with lithium
- ligand-GPCR uncoupling
- hypothyroidism/increased TSH secretion
- polydipsia
- polyuria
- aquired nephrogenic diabetes insipidus
Drug interactions with lithium
- diuretics (increase reabsorption of Li)
- aspirin and acetamenophen
- Norepinephrine (Li antagonizes NE effect on blood pressure)
- old neuroleptics: severe extrapyramidal syndrome
Act on MAO

MAO inhibitors
Act on NE reuptake
- desipramine
- maprotiline
Acto on alpha 2 receptor

mirtazapine
act on 5-HT reuptake
- fluoxetine
- trazodone

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Pharmacology Exam 4

Description

antidepressant drugs and lithium

Updated

2010-11-14T05:11:56Z

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