Psychopharmacology for Mental Health and Illness Drugs

Psychopharmacology for HLSC210 (Mental Health& Illness) North Sydney Campus Drugs- an exogenous chemical that affects one or more biological processes Drug effects: The changes a drug produces in an animal’s physiological processes and behavior. Sites of action: The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells. Pharmacokinetics: movement of drugs through the body ? Absorption Distribution Metabolism Elimination Pharamacodynamics Study of qualitative effects of drugsWhere drugs act? – four sites of action ?

Receptors (agonist and antagonist/blockers) a ? Ion channels- drugs can block or open the ion channels ? Enzymes- enzymes may be inhibited to produce greater neurotransmitter effect ? Carrier proteins-transport neurotransmitters across cell membranes Bioavailability ? Amount of drug found in systemic circulation & various tissues,especially the intended ones. ? Psychiatric drugs must pass through blood-brain barrier. ? Lipid solubility is necessary for drugs passing through blood brain barrier. Efficacy, potency and tolerance ? Efficacy -how good is the drug in diminishing the manifestations of a disorder ?

Potency – dose required to produce the desired biologic response. ? Loss of effect /tolerance ? desensitization (rapid decrease in drug effect) ? tolerance (gradual decrease in the effect of a drug at a given dose) ? can lead to being treatment refractory. Target symptoms, side effects and adverse effects ? Target symptoms: specific symptoms for each class of medication ? Side effects: responses not related to target symptoms. ? Adverse effects: unwanted effects with serious physiologic consequences. Key Neurotransmitters in the Brain ? Dopamine-skeletal muscle movements, behaviour, emesis, hormone release ?

Acetylcholine –cognition, skeletal muscle movements, memory, consciousness. ? Noradrenaline –arousal, sleep, mood, appetite, hormone release, body temperature ? GABA (gamma-aminobutyric acid) –motor control, memory, consciousness ? Serotonin-,behavior, pain transmission + as for nadrenaline ? Glutamate-learning and memory Neurotransmission ? The receptor sites are specifically structured to bind with neurotransmitters. ? Soon after the neurotransmitter is released, it must quickly be inactivated and postsynaptic neuron to be able to receive new messages.

Synapse: a junction that mediates information transfer from one neuron to another neuron or to an effector cell. Components of synapse are- presynaptic terminal, synaptic cleft and postsynaptic membrane. Most common means of inactivation of NTs ? Enzymatic degradation ? Reuptake- neurotransmitter is transported back into the presynaptic neuron where it is repackaged into the vesicles. 1 Psychopharmacology » Subspecialty of pharmacology that includes medications affecting the brain and behaviour and used to treat mental disorders. ? Anti anxiety medications ? Antipsychotics ?

Antidepressants ? Mood stabilizers(anti-maniac) Drugs that reduce anxiety and induce sleep ? Benzodiazepines ? diazepam (Valium) ? lorazepam (Ativan) ? alprazolam (Xanax) ? Clobazam ? Nonbenzodiazepines ? busipirone (BuSpar) ? zolpidem (Ambien) ? Antihistamines Antianxiety (sedative-hypnotic) medication Benzodiazepines: Pharmacodynamics ? act by binding to a specific regulatory site on GABAA receptors and increases affinity of GABA binding to GABAA receptors ? chloride channels open & chloride ions move into cell, hyperpolarising the membrane? neuronal inhibition Pharmacological effects ?

reduction in anxiety and aggression ? sedation and induction of sleep ? reduction of muscle tone and coordination ? antiepileptic Indications ? anxiety disorders, sleep disorders ? seizure disorders ? preoperative medication ? muscular spasms ? alcohol withdrawal Adverse effects Common (sedation and CNS depression) ? drowsiness, confusion, lack of coordination, ? double vision, amnesia, ? vertigo, slurred speech ? Tolerance and dependence Less frequently ? headache, hypotension, anger, ? impaired concentration, ? hallucinations, paradoxical insomnia Drug interactions ?

Other CNS depressants: synergistic effects Contraindications Avoid in elderly people and children 2 » Antidote to benzodiazepine overdose ? Emetics /gastric lavage with a endotrachael tube ? Flumazenil : a competitive antagonist at benzodiazepine receptors,reverses sedative effects (IV administration) Drugs that is effective in relieving symptoms of schizophrenia Types of antipsychotic drugs Conventional/Typical ? Phenothiazines (chlorpromazine, prochlorperazine) ? Thioxanthenes (Navane) ? Haloperidol (Haldol, droperidol) Atypical or Novel ? Clozapine (Clozaril) ? Olanzapine (Zyprexa) ? Risperidone (Risperdal) ?

Aripiprazole Pharmacodynamics of typical antipsychotic drugs ? competitive blockade of D2 receptors ? competitively block other CNS neurotransmitters: 5-HT, ACh, Nad and histamine Pharmacokinetics ? dose/response unpredictable (dosage trial) ? several weeks to take effect ? Metabolism and excretiom- liver ? accumulates in fatty tissues ? 1/2 life of 24 hours or more Adverse effects Extrapyramidal effects ? Dystonia: involuntary muscle spasms, abnormal postures, torticollis, oculogyric crisis, ? Parkinsonism: rigidity, akinesia (slow movement), tremor, masklike face. ? Akathisia: inability to sit still, restlessness ?

Tardive dyskinesia: irregular repetitive involuntary movements of mouth, face, and tongue, including chewing, tongue protrusion, lip smacking, puckering of the lips, and rapid eye blinking. ? Abnormal finger movements Endocrine and sexual ? hyperprolactinaemia ? amenorrhoea, galactorrhoea ? sexual dysfunction, gynaecomastia ? weight gain (blocking histamine receptor) ? sedation ? anti-cholinergic effects ? cardiovascular – orthostatic hyportension ? blood dyscrasias – agranulocytosis Antipsychotic medications Atypical/novel agents They are selective antagonist for 5HT2 & D 2 receptor and no affinity for muscarinic receptors.

Adverse effect ? tendency for weight gain ? hyperglycaemia and orthostatic hypotension 3 » Drugs that alleviate the symptoms of depressive illness. Types of anti-depressants ? tricyclic antidepressants (TCAs) ? selective serotonin reuptake inhibitors (SSRIs) ? monoamine oxidase (MAO) inhibitors Tricyclic anti-depressants (TCAs) ? Amitriptyline ? Imipramine Pharmacodynamics ? inhibit reuptake of NAd and/or 5-HT by blocking carrier protein Pharmacokinetics ? delayed onset of action ? adjunct therapies may be required Adverse effects ? headach, dizziness, increased appetite Selective 5-HT uptake inhibitors (SSRI) ?

Fluoxetine (Prozac) ? Sertraline(Zoloft) ? Paroxetine (Paxil) ? Citalpram Pharmacodynamics ? inhibit reuptake of 5-HT Pharmacokinetics ? delayed onset of action ? adjunct therapies may be required Adverse effects ? anorexia, nausea and weight loss ? dizziness, headache, rash ? suicidal tendency Drug interactions MAO inhibitors – serotonin syndrome Monoamine oxidase inhibitors (MAOIs) Enzymes (MAOA, MAOB) found in mitochondrial membranes of nerve terminals that inactivates and degrades tyramine and catecholamines. Pharmacodynamics Inhibit enzyme responsible for the metabolism of serotonin, dopamine, norepinephrine, and tyramine.

Increases levels of norepinephrine and serontonin in the CNS. ? Selective MAOA inhibitors eg. Moclobemide, is inhibitors of MAOA and effects are reversible. (MAOB can still degrade tyramine). ? Foodstuffs rich in tyramine (eg, cheese, red wine, vegemite etc. ) must be restricted in individuals taking non-selective(irreversible) MAOI. ( may cause hypertensive crisis due to widespread release of noradrenaline in the periphery, that is not degraded) Adverse effects-hypertensive crisis,nausea, insomnia, dizziness. Anti-depressants 4.

Drugs that alleviate the symptoms of mania Lithium (Lithium Carbonate) Action: uncertain, crosses cell membranes, altering sodium transport, not protein bound Pharmacodynamics ? unknown Pharmacokinetics ? rapid oral absorption ? half-life 24 hours in adults ? narrow therapeutic range Pharmacological effects ? inhibits NT release at synapses ? increases turnover NA and 5-HT ? decreases receptor sensitivity Adverse effects ? thirst, metallic taste, ? increased frequency or urination, ? fine head and hand tremor, drowsiness, and ? mild diarrhea lithium toxicity – severe diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination.

Avoid during pregnancy. Other Mood Stabilizers drugs: (anticonvulsant) ? Carbamazepine (Tegretol) ? Valporate (Valpro) Used only when patients have not responded to lithium Pharmacodynamics Possibly enhancement of GABA activity Pharmacokinetics Metabolism and excretion-Liver metabolized by P450 system (potential drug-drug interaction) Adverse Effects ? Nausea, and vomiting ? Dizziness, drowsiness, tremor, ? visual disturbances, ? Weight gain ? Alopecia (hair loss) __________________________________________________________________________ (The end) » Mood Stabilizers: (Antimanic therapy) 5.

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