Pharmacology Flashcards
What’s another name for Bipolar Disorder?
Manic-depressive illness
What are the signs and symptoms of Bipolar Disorder?
Periods of unusually intense emotion, changes in sleep patterns and activity levels, and unusual behaviours - these are called mood episodes.
What are the symptoms of the depression phase of Bipolar Disorder?
Sadness, anxiety, loss of energy, hopelessness and trouble concentrating, lose interest in activities, gain or lose weight, sleep too much or too little, think about suicide
What are the symptoms of manic episode/phase of Bipolar Disorder?
Feeling super-charged, talking more, easily distracted, thoughts race, don’t sleep enough - leads to reckless behaviour. Three or more of these symptoms nearly everyday for a weak, is a sign of manic episode.
What is a mixed episode in bipolar disorder?
Having depression and mania symptoms at the same time or very close together - manic or depressive episode with mixed features - leads to unpredictable behaviour such as taking dangerous risk when feeling hopeless but energized.
What is Psychosis and what are the signs and symptoms of it, in Bipolar Disorder?
A mental state - when the person affected has lost contact with reality.
- Hallucination - false sensory perceptions
- Delusion - False beliefs held with absolute certainty
- Disruption in thought process
- Schizophrenia - a primary psychotic condition
What causes mania episodes?
A functional excess of monoamine Neurotransmitters
What are the different counselling/therapies available to those with Bipolar Disorder?
- Cognitive behavioural therapy = focuses on changing thoughts and behaviours that accompany mood swings
- Interpersonal therapy = aims to ease the strain bipolar disorder puts on personal relationship
- Social rhythm therapy = helps people to develop and maintain daily routines
What are the treatments for Bipolar Disorder?
1st Line: Antipsychotic drugs such as Olanzapine, Risperidone, Quetiapine, Aripiprazole
2nd Line: Li+ ion
3rd: Antiepileptic drugs such as Valproic acid, carbamazepine
How long do Li+ ion take to work?
Therapeutic effects start in around 5 days and take several weeks for full effects
How long do the third line treatment take to work?
Several weeks for full effects
What social treatments are available for Bipolar Disorder?
Support Groups such as:
- Depression n Related Affective Disorder Association (DRADA)
- Depression and Bipolar Support Alliance (NDMDA)
Rehabilitation and habilitation
What is the Mechanism of Action for Li+?
The exact mechanism is for Lithium is not known.
But it is thought that Lithium might work by enzyme inhibition - the non-competitive inhibition of inositol monophosphate, which effects the Phosphatidyl inosol (PI) pathway and causes PI depletion.
Or that Lithium may be enhanced by the deactivation of the Glycogen synthase kinase (GSK-3B).
What is the Pharmacokinetics of Li+?
Lithium is taken by mouth as a carbonate salt.
Li+ enters the cell freely through several channels and ion-coupled transporter that normally serve for Na+
It is excreted by glomerular filtration but Li+ is nephrotoxic.
What are the drug interactions for Lithium?
Diuretics reduce renal lithium secretion (there’s an increase in the re-absorption of Na+ and Li+ in proximal tubule)
? NSAIDS and Ang II rec antagonists reduce renal clearance? (slide 14) - check with Tanyas 100 drug books
When taken with SSRI or MAOIs, it can cause serotonin syndrome
ACE inhibitors increase serum lithium concentrations; examples include Ramipril, Lisinopril, Enalapril etc.
What are the adverse reactions of Lithium?
At low dose: dry mouth, increased thirst and urination
Poisonous at high doses - above 1.5mM it produces a variety of toxic effects
Overdose: coma convulsions, loss of consciousness, death
Long term: hypothyroidism, diabetes insipidus
How must Lithium be given?
It must be give as modified release formulations to avoid high Cmax
And must be monitored regularly
What are the cautions of Lithium?
Pregnancy - can cause teratogenesis
Renal and thyroid function is tested before starting therapy
At what age do people usually have Schizophrenia?
Between the ages of 15 to 35
What are some causes of Schizophrenia?
- Genetic links
- Damage - to the brain during pregnancy or birth
- Stress
- Recreational drugs - ecstasy, LSD, cannabis, crack and amphetamines (speed)
What are the positive symptoms of Schizophrenia?
- Delusions
- Hallucinations
- Thought disorder
- Abnormal, disorganised behaviour
What are the negative symptoms Schizophrenia?
- Withdrawal from social contacts
- Flattening of emotional responses
- Emotional responses out of context
- Reluctance to perform everyday task
What brain abnormalities do patients with Schizophrenia have?
- Enlarged Ventricles which implies loss of brain cells and which causes poor performance on cognitive test, poor premorbid adjustment and poor response to treatment
- Reduced activity in prefrontal cortex
How are Dopamine and Schizophrenia linked?
It is hypothesised that Schizophrenia is caused by an over-activity of dopamine. That there are six time as many D4 dopamine receptors as normal brains.
Which may intensify brain signals and lead to positive symptoms
Examples:
- Amphetamine - causes paranoia, delusions, auditory
- Phenothiazines and other typical neuroleptics block D2 receptors and alleviate positive symptoms
Where are the Principle Dopaminergic Tracts located?
Nigrostriatal tract (extrapyramidal pathway) - begins in the substantia nigra and ends in the caudate nucleus and putamen of the basal ganglia
Mesolimbic tract - orginiates in the midbrain tegmentum and innervates the nucleus accumbens and adjacent limbic strcutures
Mesocortical tract - originates in the midbrain tegmentum and innervates anterior cortical areas
Tuberoinfundibular tract - projects from the arcuate and periventricular nuclei of the hypothalamus to the pituitary
Where are the Principle Dopaminergic Tracts located?
Nigrostriatal tract (extrapyramidal pathway) - begins in the substantia nigra and ends in the caudate nucleus and putamen of the basal ganglia
Mesolimbic tract - orginiates in the midbrain tegmentum and innervates the nucleus accumbens and adjacent limbic strcutures
Mesocortical tract - originates in the midbrain tegmentum and innervates anterior cortical areas
Tuberoinfundibular tract - projects from the arcuate and periventricular nuclei of the hypothalamus to the pituitary
How do conventional anti-psychotic drugs work?
They block CNS dopamine receptors in mesolimbic pathways as they have a high affinity to the family of D2 receptors.
They are rapidly absorbed from the gut but undergo extensive first-pass metabolism.
How are conventional anti-psychotic drugs eliminated?
Eliminated by metabolism in the liver
Examples of conventional antipsychotic drugs?
Chlorpromazine
Trifluoperazine
Perphenazine
Fluphenazine
Thioridazine
Haloperidol
Thiothixene
Mesoridazine
Loxapine
Molidone
Pimozide
What are the adverse reactions for conventional anti-psychotic drugs?
- Drowsiness and cognitive impariment
- Hypothermia
- Reduced seizure threshold
- Hypersensitivity
- Weight gain
- GI disturbance
- Withdrawal symptoms
- Extrapyramidal effects
What are extrapyramidal effects?
DAergic neurons in the nigrostriatal pathway regulates the extrapydramidal system that contributes to the contol of movement.
This causes:
Acute dystonia - involuntary contractions of muscles
Tongue protrusion - Tongue extending beyond ridges or teeth
Toricollis - one side of the neck becomes painful
Oculogyric crisis - spasmodic movements of the eyeballs into a fixed position
Akathisia - restlessness
Pseudoparkinson - imitates the symptoms of Parkinson’s disease eg. slow speech, muscle stiffness.
Tardive dyskinesia - sudden, irregular movements which you cannot control
What is mechanism for atypical antipsychotic drugs?
They block serontin dopamine receptors, but to a lesser degree. And they block receptors for Na, histamine, acetylcholine.
Rapidly absorbed from the gut but undergoes first-pass metabolism to inactive metbolities
Examples for atypical antipsychotic drugs?
Clozapine
Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole
What atypical drug is more effective than conventional antipsychotic drugs?
Clozapine
What are the adverse reactions of atypical antipsychotic?
- Agranulocytosis
- Hyperglycaemia
- Weight gain with clozapine and olnazapine
- Withdrawal symptoms
Which Antipsychotics are first choice drugs?
Atypical antipyschotics (other than clozapine) are first choice drugs. This is because they are less likely to cause extrapyramidal effects, they work better on negative symptoms and less chance of relapse.
However, they have long term consequences of weight gain.
What causes Epilepsy?
Epilepsy results from paroxysmal uncontrolled discharges of neurons within the CNS
What happens during an epilepsy episode?
The manifestations range from a major motor convulsion to a brief period of lack of awareness.
The following are altered:
- consciousness
- motor activity
- sensory phenomenon
- unusual behavior
What are the two classifications of Epilepsy?
- Partial (Focal) Seizures
- Generalized seizures
What are the different types of Partial (focal) seizures?
Simple partial seizures - this has motor, somatosensory or psychic symptoms. This is usually no loss of consciousness.
Complex partial seizures - This has temporal lobe or psychomotor and usually has loss of consciousness
These seizures usually begin locally, often resulting from focal structural lesion in the brain. This may remain localized or progress to generalized seizures (spread to the entire cortex)
What are the different types of generalized seizures, and what are the characteristics?
Tonic-Clonic seizures (Grand Mal) - Initial rigid extensor spasm, respiration stops, defecation, micturition and salivation occur and violent synchronous jerks
Absence seizures (Petit Mal) - Brief losss of awareness (may be described as daydream or not paying attention), no loss of posture tone, may occur 100+ times a day, primarily pediatric problem, usually disappears as child matures
Myoclonic - Seizures of a muscle or group of muscles
Atonic - Loss of muscle tone / strength
Status - A condition when consciousness does not return between seizures for more than 30 min. Has potential for the development of pyrexia, deepening coma and circulatory collapse. Death occurs in 5-10%.
These affect the whole brain with loss of consciousness
What causes epilepsy?
Anything that causes injuries to the brain can cause seizures
Describe how seizures develop?
- Unbalance of excitatory and inhibitory neurotransmission
- Excitation (too much)- inward Na+, outward Ca++ currents; neurotransmitter involved is glutamate and aspartate
- Inhibition (too little)
- inward Cl-, outward K+ currents’ neurotransmitter involved is GABA
- Abnormal electrical properties of the affected cells, causing sudden excessive and asynchronized neuronal firing
- May have no obvious stimulus or may be due to trauma, hypoglycemia or infection
Explain the movement of of ions in Epilepsy?
Action potential occurs when membrane potential crosses threshold. Na+ channels then open and Na+ begins to enter cell. K+ channels open ad K+ begin to leave cells. Na+ channels become refractory, no more Na+ enters cell. K+ continues to leave cell, causes membrane potential to return to resting level . K+ channels close, Na+ channels reset. Extra K+ outside diffuse away.
