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Medical Pharmacology of Neurology and Mental Health
Drugs used in common neurological and mental health disorders including dementia, psychosis, depression and anxiety. Plus drugs of abuse.
79
Medical
Undergraduate 3
08/06/2013

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Term
In which conditin is Donepezil indicated and what is it's mechanism of action?
Definition
Donepezil is indicated in early stage Alzeihmers.  It is an ACh-esterase inhibitor
Term
Galantamine is also indicated in the treatment of Alzheimers.  How does it differ from Donepezil?
Definition
Galantamine is competetive and reversible, which means that its effect is dose related.  Clinically it is very similar.
Term
This drug is used later in the course of Alzheimers disease. It is a glutamate antagonist.
Definition
Memantadine.
Term
The group action of the antipsychotic family is as?
Definition
Dopamine receptor antagonists
Term
The dopamine theory of schizophrenia proposes that?
Definition

Schizophrenia is due to a disturbed and hyperactive dopaminergic signal pathway. 

 

 

 

Term
Compare and contrast Haloperidol and Chlorpromazine.
Definition

Both drugs are typical antipsychotics.  Both have EPSE and sedative effects, however Chlorpromazine has more AE, including: weight gain, hypotension and antimuscarinic effects.  

 

 

Term
The patient prescribed a typical antipsychotic is generally an elderly, dementing patient.  Why is this?
Definition
  • At low doses there is a decreased likelihood of significant AEs.  
  • Typical antipsychotics are sedatives which can improve QoL of dementing patients.
  • Anticholinergic side effects include urinary retention, which is useful in counteracting incontinence.
Term
What are three common atypical antipsychotics?
Definition
Quetiapine, Clozapine, Olanzepine, Risperidone, Aripiprazole.
Term
What are the advantages and disadvantages of atypical antipsychotics?
Definition

Atypical antipsychotics have far fewer EPSE.  

They are more likely to cause disordered metabolism, leadin to weight gain, insulin resistance.  

They are mostly sedatives.

They are very expensive.

Term
Compare and contrast one typical and one atypical antipsychotic?
Definition

Haloperidol has significant EPSE, but few other side effects.  It is relatively cheap.

Clozapine has almost no EPSE, but will cause sedation, hypotension, anticholinergic symptoms and weight gain.  It is rather expensive.

Term
EPSEs consist of 4 main syndromes?
Definition

Akathisia- restlessness and irritability

Dystonia - rigidity 

Parkinsonism - bradykinesia, shuffling gate, cog wheel rigidity 

Tardive dyskinesia - abnormal, involuntary movements

 

Term
EPSEs are most often caused by antipsychotics (esp. Haloperidol accumulative effect) but can also be caused by?
Definition
metoclopramide, TCAs and SSRIs
Term
EPSE incidence can be reduced by dose titrating antipsychotics.  How do you treat EPSE?
Definition

EPSEs can be treated with either antimuscarinic (anticholinergic) agents such as Benztropine (Congentin).  It antagonizes ACh and balances effect of dopamine.

 

Pramiprexole is a dopamine agonist and can be used to treat EPSE.

Term
Antipsychotics are indicated as first line treatment of which uncomplicated major condition?
Definition
Schizophrenia
Term
Are antipsychotics more effective at managing positive or negative symptoms of schizophrenia?
Definition
Positive symptoms: hallucinations and delusions.
Term
A schizophrenic patient with poor compliance may benefit from which antipsychotic administered IM.
Definition
Risperidone has a long action and can be administered IM.
Term
Antipsychotics may cause this rare but lethal condition?
Definition

Neuroleptic malignant syndrome.  It is characterised by hyperpyrexia, altered LOC and rigidity.

 

Classically NMS has very high creatine kinase.

Term
Chlorpromazine requires regular WCCs.  Why?
Definition
Chlorpromazine may cause agranulocytosis.
Term
Antipscychotic medications may cause abnormal ECG changes.  What would be most likely?
Definition
QT prolongation, leading to ventricular arrythmias.
Term
Describe briefly the monoamine theory of depression?
Definition
Depression is caused by an impairment of the monoaminergic system.  Particularly, deficiencies in the concentration of 5-HT and dopamine.
Term
Obviously antidepressant are used in the treatment of depression, however they are also used in the management of?
Definition
Anxiety, bipolar and OCD.
Term
The main classes of antidepressants are?
Definition
TCA, MOA inhibitors and SSRIs.
Term
TCA group mechanism of action?
Definition
Non-selectively inhibit the reuptake of 5-HT and NA.
Term
SSRI mechanism of action?
Definition
SSRIs are highly specific and effective inhibitors of serotonin reuptake by the presynaptic nerve.  Therefore increasing concentration of serotonin in the synaptic gap.
Term
Compare and contrast TCAs and SSRIs?
Definition

Both drugs are equally effective in treating depression.

 

TCAs are associated with significantly more AEs including anticholinergic effects, antihistaminergic and cardiotoxic.  Severly sedative.

 

SSRIs are more heavily associated with headaches, agitation and tremours.

 

Both cause sexual dysfunction.  SSRIs cause ejaculatory delay.

 

TCAs are indicated in in-patient management and severe, resistant depression.

Term
List two examples of TCAs?
Definition
Amitriptyline and Imipramine
Term
Imipramine is an effective antidepressant in post-menopausal women due to a particular double-effect.  Why?
Definition
Because urinary retention (an AE) may help in the treatment of nocturnal incontinence.
Term
What class of drug is Moclobemide, and what is its MoA?
Definition
Moclobemide is a MAO inhibitor indicated in depression and social anxiety.
Term
Sertraline, Paroxetine and Fluoxetine are which class of drugs?
Definition
SSRI- indicated as first-line management in depression.
Term
Compare and contrast paroxetine and fluoxetine?
Definition

Paroxetine has a significant sedative effect where as fluoxetin (Prozac) can induce anxiety and hyperactivity.

 

Fluoxetine is infamous for causing sexual dysfunction and weight loss.  Contraindicated in hepatic impairment.

 

Both are indicated in the treatment of MDD.

Term
Lithium is used to treat?
Definition

The manic episodes of bipolar disorder.  As well as prophylactically to prevent the onset of mania in schizophrenia.   

 

The classical patient is the resistant bipolar patient who has tried without success 6 months of mood stabilizing anticonvulsants (Carbemazepine).

Term
The most significant global side effect of Lithium is?
Definition
Massive fluid output leading to polyuria, dehydration and SIADH (syndrome of inappropriate antidiuretic hormone production)
Term
What is one (1) significant contraindication of TCA use?
Definition
Concurrent MAOi use.
Term
TCAs and SSRIs: one is typicall given in the morning and the other in the evening. Which is which?
Definition

SSRI morning

TCA evening

Term
Serotonin syndrome can be caused by?
Definition

Serotonin withdrawal

MAOi and SSRI polypharmacy

Clinically: tremour, hyperthermia and cariovascular symptoms.

Term
Describe Lithium's therapeutic index
Definition
Lithium has a very narrow therapeutic index.  Dose must be adjusted according to plasma levels.  Unusual excretion means lithium requires regular serum monitoring.
Term
Which family of drugs are indicated in the prophylactic management of bipolar disorder?
Definition
The mood stabilisers (i.e. antiepileptic drugs)
Term
What are the most common mood stabilisers?
Definition
Carbemazepine, Valproate, Lamotrigine, Topiramate and Phenytoin
Term
What is the mechanism of action of Carbamazepine and when is it indicated?
Definition

Carbamazepine works by decreasing the excitability of the neuronal cells by altering the permeability of the membranes.

Carbamazepine is indicated as second line management of bipolar disorder.  It is most effective in rapid cycling bipolar or a schizoaffective picture.

Term
Which anticonvulsant has superceded Carbamazepine as the mood stabiliser of choice.
Definition
Sodium Valproate
Term
In what clinical picture would Lamotrigine be the better drug of choice for bipolar?
Definition
When there is a significant depressive component.
Term
What is the main clinical benefit of adding Topiramate to a psychotropic drug regime.
Definition
Topiramate is indicated in the treatment of bipolar and induces weight loss; which may counter act the weight gain caused by the atypical antipsychotics.
Term
What life threatening skin rashs are associated with Lamotrigine use?
Definition
Stevens-Johnson syndrome and toxic epidermal necrolysis.  Cell death causes the epidermis to separate from the dermis.
Term
Describe the typical management of an uncomplicated bipolar patient.
Definition

Maintenance with Lithium.  Plus an additional mood stabiliser, potentially sodium valproate.

 

Second line treatment, may respond better to antipsychotics.

 

To manage symptoms while medications begin to work, use benzodiazepines.

 

Omega 3 fatty acids have some evidence to suggest benefit to negative symptoms.

Term
What is the group effect if the benzodiazepines (anxiolytics)?
Definition
Benzodiazepines are GABA agonists.  GABA is an inhibitory NT, therefore an agonist increases the inhibitory effects causing sedation, bradycardia and muscle relaxtion.
Term
Benzodiazepines are commonly used for there ... effects?
Definition
Hyponotic, sedative, anticonvulsant, antianxiety and muscle relaxant.
Term
Benzos are used with caution in the elderly because?
Definition
The common side effects of benzos are to induce drowsiness, dizziness and loss of coordination.  These three factors contribute to falls.
Term
Benzos are contrindicated in patients with compromised respiration because?  Give an example of such a patient?
Definition
They can cause respiratory depression.  COPD.
Term
If unavoidable, which benzos are preffered in the elderly, short or long?
Definition

 Oxazepam or Temazepam would be preffered in the elderly, as they are short acting.  

 

High potency and long acting are not recommended in the elderly i.e. Triazolam and Alprazolam

Term
Would you expect to see withdrawal symptoms with long term benzo use?
Definition
Yes
Term
Advantages and disadvantages of short acting benzo?  Give an example?
Definition
Midazolam is a short acting benzo. They have far fewer residual effect if taken before sleep.  Increased risk of abuse and withdrawal.
Term
Temazepam is an example of an?
Definition
Intermediate acting benzo.
Term
Advantages and disadvantages of long acting benzodiazepine?  Example?
Definition
Diazepam is a long acting benzo.  There is increased risk of accumulation which may have adverse effects on hepatically impaired patients.  However there is decreased risk of abuse and withdrawal.
Term
Gabapentin is used for?  Common side effects?
Definition

Gabapenin is used for the relief or neuropathic pain, seizures and bipolar.

 

Gabapentin shares the family AEs of antianxiety drugs.  Sedation, dizziness, drowsiness, drooling, respiratory depression, peripheral edema.  Increased risk of suicidal tendencies.  Risk of withdrawal and abuse leading to OD.

Term
Clonazepam length of action most closely correlates to diazepam or midazolam?
Definition
Diazepam, it is long acting.   It is a high potency benzo.
Term
What are the 6 major toxidromes?
Definition
Anticholinergic, cholinergic, hallucinogenic, opioid, sympathetic and hypnotic.
Term
Compare and contrast anticholinergic and cholinergic?
Definition

Anticholinergic is constipation, blurred vision, urinary retention, tachycardia, dry mouth and memory impairment.  Caused by antihistamines, antiparkinsons, antidepressant and antipsychotics.

 

Cholinergic: SLUDGE salivation, lacrimation, urination, diarrhea, GIT upset, emesis.

Term
Describe the classic traid of the opioid toxidrome?
Definition
Pin point pupils, altered LOC and respiratory depression.
Term
What are the typical clinical signs of a hallucingenic toxidrome?  Common causes?
Definition
Seizures, tachycardia, tachypnoeaic, hypertensive.  Caused by cocaine, ecstasy and amphetamines.
Term
Treatment of opioid overdose?
Definition
Naloxone (Narcan) is a competitive mu receptor antagonist.
Term
Most common causes of sympathamimetic toxidrome?  Clinical signs?
Definition

Prescription drug overdoses.  Pseudoephidrine, beta blockers, antoconvulsants.  

 

Diaphoresis, anxiety, seizures, hyperreflexia.

Term
Alcohol overdose produces a sedative toxidrome, it is characterised by?
Definition
Coma, slurred speech, blurred vision, ataxia and delirium.
Term
Synthetic opioid used in heroin withdrawal subsitution?
Definition
Methadone
Term
Used to reverse benzodiazepine overdose?
Definition
Flumazenil.  Flumazenil has a short half life and requires regular readmission.
Term
This anticonvulsant can cause immune compromise and bleeding disorders.
Definition
Carbamazapine
Term
Anticonvulsant associated with birth defects due to folate interactions?
Definition
Phenytoin
Term
Compare and contrast benzos and barbituates?
Definition
Benzos have a better side effect profile, decreased potential for abuse and decreased interactions.
Term
Trazodone works by ... and is indicated in?
Definition
Trazodone is an alpha adrenergic antagonist indicated in depression, anxiety and insomnia.  It can decrease BP effectively.
Term
Is Lorazepam a long or short acting benzo?
Definition
Short - like Midazolam
Term
SSRIs are first line agents in depression and?
Definition
Anxiety disorders.
Term
Quetiapine is associated with which debilitating eye condition?
Definition
Cataracts
Term
Compare and contrast the roles of Risperidone and Olanzapine in bipolar disorder.
Definition
Both can be administered IM, making compliance a lesser issue.  Risperidone is for management of stable condition where as Olanzapine is indicated in acute exaccerbations of manic episodes.
Term
Can benzodiazepines be used to treat tardive dyskinesia?
Definition
No, idealy this would be treated by titrated antipsychotic dosage.  Alternatively with an anticholinergic or dopamine agonist.
Term
Buproprion is a popular add on to depression management, unfortunatey it carries what risk?
Definition
It lowers seizure threshold
Term
Venlafaxine is a part of which drug group?
Definition
Venlafaxine is a SNRI indicated in MDD and general anxiety disorder.  It can cause glaucoma.
Term
What is the main antiparkinson's drug in use?
Definition
Levedopa/carbidopa.  L-Dopa is the precursor to dopamine, adrenalin and NA.  Carbidopa prevent peripheral conversion.
Term
Amantadine is?
Definition
An antiviral drug indicated in the tretamnet of parkinsons disease.  It is a weak NMDA glutamate antagonist and increases dopamine release.
Term
This drug is used in the treatment of pituitary tumours, parkinsons disease and hyperprolactenemia.  What is it and what is its MoA?
Definition
Bromocriptine is a dopamine agonist.
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