2 Mood influencing agents

Lithium carbonate

Mood Stabilizers (Normotimic agents)

clinical relevance: reduce manic and deptressive phases,stabilzed patients mood

• A. Li influences secondary signaling, eg

• 1) Inhibition of inositol monophosphatase by inhibition of cascade of IP3 and DAG signals;

• 2) Inhibits glycogen synthetase kinase 3 (GSK-3)

• B. Reduces cation transport through cell membranes in neurons and myocytes,

indication: bipolar disorder

side effect: : tinnitus, aphasia, visual disturbances, hypothyroidism, Li inhibits the action of antidiuretic hormone (ADH) in the kidneys. Narrow therapeautc index. Required renal function as is naturealy excreted

Antidepressants

• serotonin dysfunction → impulsivity disorders

• norepinephrine disorders → Loss of interest and energy

• dopamine dysfunction →D ecreased motivation

Noradrenergic tract Locus coeruleus and prefrontal cortex

Serotoninergic tract Raphe nuclei and prefrontal cortex

SERT, NET, DAT

SERT- serotonin reuptake transporter

NET-norepinephrine reuptake transporter

DAT-dopamine reuptake transporter

Amitriptyline, Nortriptyline (less intense) = NMRI

Antidepressants.psychomotor inhibition. Antidepressant, sedative, coanalgesic effect

Non-selective monoamine reuptake inhibitors

SERT & NET inhibitor

(5-HT2/H1/M1-5/a1 inhibitors)

indication: major depression, chronic neurophatic pain

side effect: 3C:cardiotoxicity, convulsions, coma, Glaucoma

Duloxetine Venlafaxine = SNRIs

Antidepressant, anxiolytic, coanalgesic effect

Selective serotonin and norepinephrine reuptake inhibitors

Inhibition of SERT and NET

indication: magod depression, anxiety, chronic neurophatic pain

side effect: nausea, vometing, sexual dysfintion, (heart)

(Interaction with MAOI- serotonin syndrome)

Paroxetine Citalopram Sertraline SSRI

Antidepressant, anxiolytic effect

Selective serotonin reuptake inhibitors (SSRI)

Selective SERT inhibition

indication: major depression, obsessive compulsive disorder, panic, anxiety, phobia

Side effect: nausea, comiting, sexual dysfunction

interaction with MAOI- seotonin syndrome, hemorrhage with anticoagulants

Bupropion SDNRI

Antidepressant, CNS stimulating effect

Selective dopamine and norepinephrine re-transporter inhibitors SDNRI

Inhibition of DAT and NET

indication - major depression, smoking (addiction)

Mirtazapine NaSSA

Antidepressant, sedative effect

Noradrenergic and Specific Serotoninergic Antidepressants

Presynaptic α2-adrenoceptor, 5HT2, 5HT3 , H1 receptor antagonist → increase Ne & 5HT

indication: major depression (sedative)

Side effect: weight gain, sedation

Serotonin syndrome

AD side effect

develops rapidly - <12 hours

problem of drug interactions - tryptophan, amphetamine, triptanes, MAO inhibitor

Symptom Triad: hyperreflexia, mydriasis, neuromuscular disorders (tremor, muscle rigidity), mental disorders

(NMS is characterized by hyporeflexia and unchanged pupil)

Effects of ANS: tachycardia, tremor, sweating, hyperthermia, mydriasis

Treatment: cyproheptadine

BENZODIAZEPINS (BZD)

Anxiolytics - Low dose sedative effect, high dose hypnotic effect

positive GABA modulator → cl influx

Flumazenil

Anxiolytic

negative GABA modulator,

BZD inhibitor

Diazepam

Anxiolytics, Long acting BZD

Anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic action

Indication - anxiety, sleep disorder, muscle spasms, seizures

Side effect: anterograde amnesia, dowsniess, respiratory depression

Midazolam

Anxiolytics. Short acting BZD

indication: anesthesia, premedication, seizures

Alprazolam

Benzodiazepine

Anxiolytics, Anxiolytic, muscle relaxant, sedative, hypnotic action

indication: panic attack, anxiety, stress (Not sedative effect)

Cl: driving

Phenobarbital

Hypnotics / sedatives, Barbituric acid derivatives or barbiturates

Positive GABA,

indication:, cardiac neurosis, vegetative agitation, sleep disorders, epilepsy

SE: Dependence,addiction problem

IA: indication of chytochomre CYP enzymes

Benzodiazepine Analogs - «Group Z», Zolpidem

Hypnotics (simular to BZD), hypnotic effect

positive GABA

indication: short term treatment of sleep disorders

Side effect: somnambulism, hallucinations

(Z drugs → sleeping drugs)