Fichas
antidepressants
Fichas del conjunto (30)
- 1a list of TCAs:Amitriptyline
Clomipramine
Dothiepin
Doxepin
Imipramine
Nortriptyline
TCAs inhibit reuptake of both
noradrenaline and serotonin into
presynaptic terminals - 2anticholinergic side effects of antidepressantsdry mouth
blurred vision
constipation
decreased sweating and saliva - 3seretonergic AEs•Feeling agitated, shaky or anxious
Feeling of being sick
•Indigestion
•Sexual dysfunction - 4Adrenergic ADRs• Relaxation of blood vessels in GI (manifesting as nausea and vomiting)
• Arrhythmias
• Widening of the pupils
Orthostatic hypotension - 5Dopaminergic side effectsPhysiological dependence
• Sleepiness
• Drowsiness
• Compulsive behaviours can take on any form (e.g., shopping, eating,
gambling, sexual activities) - 6Selective serotonin reuptake inhibitors (SSRIs)Example: Fluoxetine (famous Prozac)
SSRIs selectively inhibit the presynaptic reuptake of
serotonin (5-hydroxytryptamine or 5HT)
SSRIs:
Citalopram
Dapoxetine
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Also given for obsessive-compulsive disorder (OCD) - 7Serotonin toxicity (serotonin syndrome)Serotonin toxicity may occur with a high dose of a single drug, when >1 serotonergic agents are used together, or when changing antidepressants with an inadequate washout period between drugs. Synaptic serotonin concentration increases, overstimulating the serotonin receptors and causing:
hyperreflexia, clonus, tremor, incoordination mental state changes (eg confusion, hypomania, agitation) shivering, sweating, fever and diarrhoea. - 8Serotonin and noradrenaline reuptake inhibitorsVenlafaxine - SNRI
•Inhibition of 5HT, NA & DA reuptake
•At low doses acts like SSRIs
•Intermediate to high doses effects on NA become important
•Cross between SSRI and TCA •Metabolised to desvenlafaxine (active
metabolite, also given as a drug) - 9Reboxetine - NRIMOA:
•Inhibits NA reuptake
•Weakly inhibits 5-HT reuptake •Antagonist at alpha-2 receptors - 10Monoamine oxidase inhibitorsExample: Phenelzine (both MAO-A and –B inhibitor)
MAOIs irreversibly inhibit monoamine oxidases A and B (MAO-A and MAO-B), increasing the synaptic concentrations of adrenaline, dopamine, noradrenaline and serotonin.
Non selective (first antidepressants)
• Irreversible inhibition of MAO A & B in
CNS & periphery
• Increased brain levels of 5HT>NA >>DA
• Cheese reaction (tyramine)
• Selective MAO-A inhibitor • Moclobemide
• Reversible
• Less interaction with food
• Many drug interactions - 11St John’s WortHypericum perforatum
• MOA
• Weak MAOI
• Inhibits 5HT reuptake
• Mild depression only
• Few side effects at normal doses - 12Atypical antidepressantsMirtazapine
Tetracyclic antidepressant; postsynaptic blockade of serotonin 5HT2 and 5HT3 receptors and presynaptic blockade of alpha2-receptors. It is also a potent H1 antagonist which accounts for its sedative effects.
Moclobemide
Moclobemide reversibly inhibits monoamine oxidase (MAO); it is relatively selective for type A (MAO-A). Synaptic concentrations of serotonin, noradrenaline and dopamine are increased.
Reboxetine
Inhibits noradrenaline reuptake; weakly inhibits serotonin reuptake.
Their MOA could not be easily classified - 13Choice of ADAll approximately equal in efficacy, although individual patient response may vary markedly. No class is superior in terms of tolerability.
TCAs, SSRIs, mirtazapine and moclobemide can be regarded as first line drugs in adults.
Venlafaxine and Reboxetine are considered second line. Non-selective MAOIs are generally reserved for patients with previous good response, or when other treatments are ineffective or not tolerated.
Previous response to a drug is the best predictor of future response to treatment - 14Comparative antidepressant informationSedation: SSRIs and MAOIs tend to be less sedating than TCAs or mirtazapine
Need for adjunctive drugs: anxiolytic and sedative/hypnotic drugs are less likely to be needed at the start of treatment with TCAs or mirtazapine. Orthostatic hypotension: least likely with SSRIs, venlafaxine, reboxetine and moclobemide.
Toxicity: TCAs, MAOIs and possibly venlafaxine are more toxic in overdose than other first line antidepressants.
Weight gain: TCAs and mirtazapine are often associated with weight gain. - 15Changing antidepressantsNeed for an antidepressant-free period to prevent ADRs due to drug interactions. General considerations:
Taper antidepressants slowly to avoid withdrawal symptoms
When deciding length of changeover, consider clinical urgency
Consider drug elimination half-life
Consider the possibility of serotonin toxicity - 16Mode of Action AntipsychoticsAntipsychotic actions are thought to be mediated (at least in part) by blockade of dopaminergic transmission in various parts of the brain (in particular the limbic system).
- 17Antipsychotics•All effective antipsychotics block dopamine D2 receptors •Differential blockade of other dopamine receptors (e.g. D1) may influence therapeutic and adverse effects •Antagonism of other receptors may influence antipsychotic activity, e.g. 5HT2 antagonism with some agents.
- 18Dopamine - functions• Motor control - nigrostriatal system Deficiency results in rigidity, tremor and difficulty initiating movement
• Behavioral effects - mesolimbic system Over-activity could lead to abnormal behavior
• Endocrine control - tuberoinfundibular system*. Dopamine and dopamine agonists suppress prolactin release, dopamine antagonists may stimulate it
*Dopamine released at this site regulates the secretion of prolactin from the anterior pituitary gland. - 19Schizophrenia - Dopamine hypothesis• Amphetamine produce a syndrome similar to the ‘positive’ features of schizophrenia
• Levodopa may aggravate the condition
• Apomorphine and bromocriptine (D2 agonists); overdose produces behavioural abnormalities similar to schizophrenia
• D2 receptor antagonists are effective in controlling the positive features of the disorder
• Increased D2 receptor binding in the brains of schizophrenic subjects. Evidence of genetic variation in the D4 receptor to which some anti-psychotic drugs have high affinity - 20Anti-psychotic Drugs - Modes of ActionAnti-psychotic Drugs - Modes of Action
• All anti-psychotic drugs have inhibitory effects on the D2 receptor
• Some have actions against the D4 receptor • All have other effects - to varying degrees
• Serotonin blockade (may improve negative symptoms)
• Histamine H1 blockade (drowsiness)
• Alpha adreno receptor blockade (postural
hypotension)
All antipsychotics (summary)
• All block dopamine receptors
• Some antipsychotics also
• Block serotonin receptors
• Block cholinergic receptors
• Block alpha - 1 receptors
• Block histamine receptors - 21Typical antipsychotics (EPSE prevalent adverse effect)• Bind to D2 receptors throughout the brain. Non- specific, long-acting blockade-results in EPSE, may augment negative symptoms and cognitive dysfunction, may increase prolactin (breast secretions, irregular periods, reduced bone density, sexual dysfunction)
- 22Atypical antipsychotics (EPSE not very prevalent)Bind better to D2 receptors in parts of the brain that control psychosis than in those that cause the above side effects. Do so by either blocking serotonin or competing loosely with it
- 23Weight GainOccurs in about 40% of patients
•Mechanism seems to be associated with effects on satiety centre combined with sedation leading to lowered metabolic rate and increase in hunger and thirst
•Clozapine and Olanzapine – significant - 24LithiumLithium is the drug of choice for treatment and prophylaxis of acute mania.
- 25Valproate and carbamazepineValproate and carbamazepine are used as alternatives when lithium is considered poorly tolerated or ineffective; they are sometimes used with each other or with lithium. Valproate and carbamazepine also appear to be particularly suitable for those with rapid cycling illness (4 or more episodes a year). Lamotrigine may also be considered for depressive episodes or maintenance treatment.
- 26mood stabilizer for bipolar disorderMood stabilizers are medications that help control the highs and lows of bipolar disorder. They are the cornerstone of treatment, both for mania and depression. Lithium is the oldest and most well- known mood stabilizer. Lithium takes from one to two weeks to reach its full effect.
- 27Lithium• Widely recommended treatment for BPD • 60-80% success in reducing acute manic
and hypomanic states
• However... issues in non-compliance to take medication, adverse effects and high relapse rate.
Lithium closely resembles sodium and substitute for sodium as a charge through sodium channels. However, lithium is not pumped out as quick as sodium by the Na+/K+ – ATPase. This results in an intracellular accumulation of lithium, a partial loss of intracellular potassium and a partial depolarization of cells.
Consequently, lithium inhibits depolarization-evoked neurotransmitter release (noradrenaline & dopamine).
In addition, lithium inhibits several enzymes involved in the normal recycling of membrane phosphoinositol. This results in a depletion of PIP2, the precursor for IP3 and DAG. - 28Common side effects of lithium:•Weight gain
•Drowsiness
•Tremor
•Weakness or fatigue
•Excessive thirst; increased urination •Stomach pain
Why looking for alternative to lithium?
•Thyroid problems
•Memory and concentration problems •Nausea, vertigo
•Diarrhoea - 29Anticonvulsant as mood stabilizers for bipolar disorderValproic acid •Lamotrigine •Carbamazepine
Anticonvulsants are used in the treatment of bipolar disorder as mood stabilizers. Originally developed for the treatment of epilepsy, they have been shown to relieve the symptoms of mania and reduce mood swings. - 30Antipsychotic medications for bipolar disorderOften, antipsychotic medications are combined with a mood stabilizer such as lithium or valproic acid. Antipsychotic medications used for bipolar disorder include:
•Olanzapine •Quetiapine •Risperidone •Ariprazole •Ziprasidone •Clozapine
Información
- Descripción
- (Drugs FlashCards) pharmacology Fichas sobre antidepressants , creado por Amelia Claire el 26/09/2017.
- Creado por
- Amelia Claire
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