Psychopharmacology Flashcards
Drug class used to treat depression
Anti-depressant
Mechanism of action
They work by increasing the availability of one or more neurotransmitter (monoamines such as dopamine, norepinephrine and serotonin).
Name the classes of anti-depressants
TCA SSRIs SNRIs MAOIs Atypical antidepressants
TCA MOA
- TCA are potent inhibitor of norepinephrine
- TCAs also are antagonist histamine-H1 receptors, Alpha1-adrenergic receptors, and muscarinic receptors
- They also block voltage- sodium channel.
Adverse effects of TCA
Weight gain Sedation Nausea and vomiting Postural hypotension Dry mouth, constipation, urine retention Confusion, blurred vision Tachycardia and arrythmias
In overdose :
Cardiac toxicity
CNS toxicity
Contra-indication for TCA
Closed angle glaucoma
BPH
MI
Arrytmias
Safest TCA in pregnancy and elderly
Amitriptyline
TCA used in enuresis (loss of bladder control)
Imipramine
MOA of SSRI
Selective serotonin reuptake inhibitors (SSRIs) work by specifically inhibiting the reuptake of serotonin. – In addition to serotonin reuptake inhibition, fluoxetine has NE reuptake inhibition (clinically relevant at high doses), CYP450 2D6 and 3A4 inhibition (involved in metabolism), and serotonin 2C antagonist actions (activating effects).
Adverse effects of SSRI
Anxiety, Drowsiness, Insomnia, Nausea and vomiting, Sexual dysfunction (ejaculatory dysfunction, anorgasmia), Drug interaction, Energizing.
Contra-indications and indications
In younger age groups, TCAs rather SSRIs. Contra-indicated in adolescents/children – may potentiate suicidality.
SSRIs relatively safe in early pregnancy (late pregnancy risk of neonatal pulmonary hypertension, apnea, floppy syndrome).
5-HT in brain, gut and platelets – SSRIs block serotonin uptake in platelets, thus increased risk of bleeding; warfarin and SSRI’s contra-indicated
SSRI examples
Citalopram Fluoxetine vilazodone fluvoxamine sertraline
Name mood stabilizers and uses
Lithium
- Primarily used for treatment for bipolar mood disorder - counteracts both mania and depression
Carbamazepine
- Anticonvulsant used for treatment of neuropathic pain and control of seizures - also used as treatment for bipolar mood disorder
Sodium Valproate
- Used in treatment of bipolar mood disorder and epilepsy - also used to treat migraine headaches
Lithium MOA
Increases the volume of brain structures involved in emotional regulation.
Reduces excitatory neurotransmission and increase inhibitory neurotransmission.
Intracellular and molecular mechanisms further modulate neurotransmission.
Lithium has neuroprotective effects
Lithium side effects on CNS
Fine tremors Dysphoria Impaired memory Lack of spontaneity Slow reaction time
Lithium cardiac side effects
T-wave flattening
Arrhythmias
Cardiac arrest
Lithium renal side-effects
Polyuria Polydipsia Minimal change disease Interstitial nephritis Impaired renal function & renal failure
Lithium thyroid, skin and weight side-effects
Thyroid - Hypothyroidism - Non-toxic goiter Skin - Hair loss - Cutaneous Lesions Weight gain
Carbamazepine MOA
Carbamazepine is a sodium channel blocker. It binds to voltage-gated sodium channels causing inhibition of action potentials and decreased synaptic transmission.
Acts as a GABA agonist and a glutamate antagonist, and decreases dopamine turnover.
Carbamazepine side-effects
Drowsiness Dry mouth Dizziness Diplopia Ataxia GIT disturbances - Nausea, anorexia, constipation, epigastric discomfort
Sodium valproate MOA
Its precise mechanism of action is unclear.
Proposed mechanisms include
- Increasing GABA neurotransmission.
- Blocking voltage-gated sodium channels.
- Impacting various neuroprotective molecular pathways.
- Inhibiting histone deacetylase
Sodium valproate side-effects
Nausea, vomiting, constipation & diarrhea Fatigue & sedation Dysarthria & ataxia Skin rashes & hair loss Increased appetite Oligomenorrhea/Amenorrhea
MOA and goal of sedatives
Tranquilizers or CNS depressants.
Slow down brain activity→ calming effect on the body.
Name the commonly used sedative
BENZODIAZEPINES
Name non-benzodiazepine sedatives
Droperidol / Haloperidol
Alpha 2 agonisists → clonidine
Benzodiazepine MOA
GABA receptors are found in the:
- Limbic system
- Spinal cord
- Cerebellum
- Brainstem
Benzodiazepines enhance action of GABA (allosterically) at GABA-A receptor
o bind to A-type GABA receptors on different site from GABA binding site to enhance GABA action of opening channels, allowing entry of chloride ions → hyperpolarization
o reduce neuronal depolarization resulting in decreased action potentials
in response to increased GABA inhibitory effect the body neuoradapts and causes decreased GABA inhibition effect and increased glutamate excitability → when diazepam is stopped there is hyperexcitability/withdrawal symptoms
Classification of benzos drugs is based on the duration of action/half-life. Name one drug in each class and their half-life
Remember the order and names of the drugs by the mnemonic MOLD & remember that there is just a doubling pattern in ther elimination half-live
M→ midozalam (ultra short-acting) - less than 6 hours
O→ Oxazepam (short-acting) - 6-12 hours
L→ Lorazepam (intermediate-acting) - 12-24 hours
D→ Diazepam (long-acting) - 24 hours
Note that short acting agents have greater tendency to cause overt dependency and withdrawal
Explain the difference between short- and rapid-acting drugs
Short acting→ the effects last for a short period
Rapid acting→ the effects occur rapidly
Indications for bonzos
Acute aggressive behaviours - Lorazepam (sedating restless patient who can move around) and diazepam (for the restless patient who needs to be restrained)
- Always ensure that resuscitation equipment and flumazenil (antidote is present) because sedation can cause respiratory failure
Epilepsy – status epilepticus (state of having one seizure that lasts more than 5 minutes or having more than 1 seizure within 5 minutes without going back to normal level of consciousness between episodes)
Anaesthesia
Alcohol withdrawal syndrome/delirium tremens.
Muscle tone disorders such as acute dystonia.
Serotonin syndrome
Anxiety disorders (not favoured at all, rather use antidepressant medication like SSRIs and SNRIs)
Other - Quick relief of hypertension in drug overdoses, Treating tachycardia caused by stimulants like cocaine
What is used in dystonia
Dystonia- give biperidine
- Treatment of EPSE caused by antipsychotics
Explain the dependence mechanism
The main problem with dependency is that it can occur even after several weeks of treatment with therapeutic doses.
Without benzodiazepines, you see that GABA plays an inhibitory role on the VTA (Ventral tegmental area) where dopamine is produced. However, when benzodiazepines are used over time, you get neuroadaptation where there is decrease GABA activity in order to maintain homeostasis and overcome the drug effects. This results in disinhibition of dopamine producing neurons
How could you avoid dependence
Treatment should be kept to a minimum, reviewed regularly and discontinued as soon as possible.
Do NOT use for anxiety states
Longstanding anxiety disorders and panic disorders should be managed with counselling and low-dose antidepressants.
Although the benzodiazepines have hypnotic properties, it is not desirable to use them in the routine management of insomnia
Therapeutic relationship between client and doctor is very important:
- Patients often do not view Benzo dependence as an addiction because their doctor prescribed the medication = denial is a big problem
What are antipsychotic drugs?
Antipsychotic drugs are a class of medicines used to treat psychosis and other mental and emotional conditions
Name the two classes of antipsychotics and give examples of each
Typicals: •Chlorpromazine •Haloperidol •Flupentixol •Fluphenazine •Thioridazine
Atypicals: •Clozapine •Olanzapine •Risperidone •Aripiprazole •Lurasidone
MOA of typical antipsychotic
First generation antipsychotics act by blocking D2 receptors.
They are non-selective and therefore block D2 receptors in all areas of the brain.
They also block histaminic, noradrenergic and cholinergic receptors.
What are typical antipsychotics used for
•Schizophrenia •Schizoaffective disorder •Bipolar disorder •Severe agitation •Dementia •Delirium •Major depressive disorder with psychotic features Non-psychiatric indications: nausea, vomiting, Tourette's' syndrome, Huntington 'disease, intractable hiccups
EPSEs from typical antipsychotics
Parkinsonism, Acute dystonic reactions, Tardive dyskinesia ,Akathisia ,Neuroleptic malignant syndrome
Possible other affects of antipsychotics
Endocrine system Gastrointestinal system Cognition Seizure threshold Cardiovascular system Other side effects include blurred vision, hot flushes and weight gain
Contra-indications of antipsychotics
Known hypersensitivity Cardiac abnormalities Previous EPSEs Parkinson's disease Renal or hepatic insufficiency
Atypical antipsychotics MOA
Second-generation antipsychotics work by blocking D2 receptors as well as serotonin receptors.
5-HT2A and 5-HT2C subtypes of serotonin receptors are the most involved
Atypical antipsychotics uses
- Treatment resistant schizophrenia
- Bipolar mood disorder – mania or mixed
- Major depressive disorder
- Agitation
Atypical antipsychotics contra-indications
Prolactinoma Parkinsonism Tardive dyskinesia Severe neutropenia Bone marrow depression Previous neuroleptic syndrome
Atypical antipsychotics contra-indications
Prolactinoma Parkinsonism Tardive dyskinesia Severe neutropenia Bone marrow depression Previous neuroleptic syndrome
Side-effects of atypical antipsychotics
Weight gain , agranulocytosis, constipation, Hyperprolactinemia, Myocarditis, pericarditis, Convulsions
