CNS Pharma Flashcards
What is cheese reaction?
Certain cheese, wines, pickled meats etc contain large amounts of Tyramine. Tyramine is an indirectky acting sympathomimetic.
In a patient receiving MAO Inhibitors, this ingested tyramine escapes degradation in the intestinal wall and the liver . It reaches systemic circulation and causes release of large amount of Noradrenaline.
This can lead to hypertensive crisis and cerebrovascular accidents.
DOC for cheese reaction: Phentolamine (Non selective alpha blocker)
Therapeutic Window effect of TCAs.
Optimal antidepressant effect seen within a narrow range of plasma concentration.
Between 50-200 ng/mL.
For amitryptiline, nortryptiline, imipramine.
Side effects of TCA.
- Anticholinergic - Dry mouth, blurred vision, constipation, urine retention
- Sedation
- Increased appetite and obesity
- “Switch over” to to mania (Bipolar disorder cases where the other pole is being unmasked by TCA)
- Alpha 1 blockade: Postural hypotension
- Tremors, sweating
- Seizures
- Sexual distress
- Arrythmias (due to anticholinergic+ direct NA potentiation+ direct cardiac depression)
- Hepatotoxic
Explain Monoaminergic hypothesis and Neurotrophic hypothesis of depression.
1) Monoaminergic hypothesis
- Depression occurs due to decreased Adrenergic and Serotonergic transmission in the brain (Cortical and limbic areas)
- Anti depressant drugs increase NA and Serotonin in the brain
- The 2-3 week delay in antidepressant effect of drugs is because initially they stimulate the presynaptic Alpha2 and 5-HT1 receptors which inhibit release
- Over time, adaptive changes occur which desensitize the presynaptic receptors. Net effect is increased NA and 5-HT transmission
2) Neurotrophic hypothesis
- Depression occurs due to decreased BDNF and NGF in the brain
- NGF are required for neuroplasticity and formation of synapses
- Antidepressant drugs increase BDNF levels and promote neuroprotection and neuroplasticity
Currently accepted hypothesepis is a combination of the above two.
Name the SSRIs. What are the side effects.
(Mnemonic: Effective For Sadness, Panic and Compulsion)
Escitalopram Fluoxetine, Fluvoxamine Sertraline Paroxetine Citalopram
S/E: SSSS
- Stomach upset
- Serotonin syndrome
- Sexual distress
- Suicidal thoughts
Others: Bleeding tendency, QT prolongation by Citalopram
Name atypical antidepressants.
Trazodone
Mianserin
Mirtazapine
Bupropion
Classify antidepressants.
- RIMA (Reversible inhibitors of MAO-A) Eg. Moclobemide
- TCA (Tricyclic antidepressant) Eg. Imipramine, Amitryptiline
- SSRIs (Selective serotonin reuptake inhibitors)
- SNRIs (selective noradrenaline reuptake inhibitors) Eg. Venlafaxine, Desvenlafaxine, Duloxetine
- Atypical antidepressants
Mechanism of action of TCA.
They inhibit the reuptake of Noradrenaline and Serotonin by blocking the NET and SERT on the neuronal membrane. They increase the concentration of NA and Serotonin in the synaptic cleft, thus exerting anti depressant effect.
Mechanism of action of Typical Antipsychotic drugs.
Typical antipsychotic drugs block Dopamine D2 receptors.
Decrease dopaminergic transmission in the mesolimbic and mesocortical areas in the brain, thus exerting their antipsychotic effect.
However they only relieve the positive symptoms of psychosis(hallucinations, excitation, aggressiveness) but not the negative symptoms.
Mechanism of action of Atypical antipsychotics.
They are weak dopamine D2 blockers but strongly inihibit 5HT2 receptors.
They relieve both the positive and negative symptoms of psychosis.
ADPKD— Definition, Pathogenesis, Clinical Features.
It is a hereditary disorder characterized by multiple expanding cysts in both kidneys, which ultimately destroy the renal parenchyma and cause renal failure.
Pathogenesis:
1) Mutation of PKD1 gene (85% cases) - On Chromosome 16p - Encodes Polycystin 1
2) Mutation of PKD2 gene - On chromosome 4q - Encodes Polycystin 2
Mutations in these two proteins — altered mechanosensation by tubular cilia and altered Calcium flux— Altered tububular epithelial growth and differention — abnormal ECM interactions, abnormal cell proliferation and fluid secretion — cyst formation — cyst causes glomerular and vascular damage and causes interstitial inflammation
Morphology:
Gross- Enormous size (4kg), external surface seems only composed of cysts with no parenchyma
Microscopy-
1) Functioning nephrons are present between the cysts
2) Cysts filled with serous fluid, sometimes haemorrhagic fluid
3) Arise from different parts of the tubules and thus have different lining epithelium
Clinical features:
- flank pain
- bilateral abdominal masses
- renal colic (due to blood clots in urine)
- hypertension
- renal failure (when sufficient no. of neohrons are destroyed
What are the side effects of Antipsychotics.
1) Dose related side effects
- CNS : Sedation, Seizures
- Hypotension and arrythmia
- Anticholinergic : Dry mouth, blurry vision, constipation, urinary retention etc
- Metabolic Side effects: Insulin resistance, dyslipidemia, obesity
- Extra Pyramidal :
Drug incuded parkinsonism, Akathisia (m/c), Acute dystonia (earliest), Neuroleptic Malignant syndrome, Tardive dyskinesia
2) hypersensitivity reactions
- Cholestatic jaundice
- Rashes
- Agranulocytosis
- Myocarditis
How would you treat Acute dystonia caused by an antipsychotic drug?
Centrally acting Anticholinergic is used.
DOC: Trihexyphenidyl/Benzhexol
Alternatives: Biperiden/ Benztropine
Or, an antihistaminic with high Anticholinergic action may be used
Eg. Promethazime, Diphenhydramine
How to treat Tardive dyskinesia?
DOC: Valbenazine or Deutetrabenzine (VMAT2 inhibitors)
Or change to atypical antipsychotics.
What is Malignant neuroleptic syndrome? How would you treat it?
It is the most severe extra pyramidal side effect of antipsychotic drugs. Characterized by - Hyperthermia - Rigidity - Hypotension - Tremors
Treatment: I.V Dantrolene is DOC
More specific drug is Bromocriptine
