Pharmacology

Question 1

What’s another name for Bipolar Disorder?

Answer 1

Manic-depressive illness

Question 2

What are the signs and symptoms of Bipolar Disorder?

Answer 2

Periods of unusually intense emotion, changes in sleep patterns and activity levels, and unusual behaviours - these are called mood episodes.

Question 3

What are the symptoms of the depression phase of Bipolar Disorder?

Answer 3

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

Question 4

What are the symptoms of manic episode/phase of Bipolar Disorder?

Answer 4

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.

Question 5

What is a mixed episode in bipolar disorder?

Answer 5

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.

Question 6

What is Psychosis and what are the signs and symptoms of it, in Bipolar Disorder?

Answer 6

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

Question 7

What causes mania episodes?

Answer 7

A functional excess of monoamine Neurotransmitters

Question 8

What are the different counselling/therapies available to those with Bipolar Disorder?

Answer 8

• 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

Question 9

What are the treatments for Bipolar Disorder?

Answer 9

1st Line: Antipsychotic drugs such as Olanzapine, Risperidone, Quetiapine, Aripiprazole

2nd Line: Li+ ion

3rd: Antiepileptic drugs such as Valproic acid, carbamazepine

Question 10

How long do Li+ ion take to work?

Answer 10

Therapeutic effects start in around 5 days and take several weeks for full effects

Question 11

How long do the third line treatment take to work?

Answer 11

Several weeks for full effects

Question 12

What social treatments are available for Bipolar Disorder?

Answer 12

Support Groups such as:
- Depression n Related Affective Disorder Association (DRADA)

• Depression and Bipolar Support Alliance (NDMDA)

Rehabilitation and habilitation

Question 13

What is the Mechanism of Action for Li+?

Answer 13

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).

Question 14

What is the Pharmacokinetics of Li+?

Answer 14

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.

Question 15

What are the drug interactions for Lithium?

Answer 15

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.

Question 16

What are the adverse reactions of Lithium?

Answer 16

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

Question 17

How must Lithium be given?

Answer 17

It must be give as modified release formulations to avoid high Cmax

And must be monitored regularly

Question 18

What are the cautions of Lithium?

Answer 18

Pregnancy - can cause teratogenesis

Renal and thyroid function is tested before starting therapy

Question 19

At what age do people usually have Schizophrenia?

Answer 19

Between the ages of 15 to 35

Question 20

What are some causes of Schizophrenia?

Answer 20

• Genetic links
• Damage - to the brain during pregnancy or birth
• Stress
• Recreational drugs - ecstasy, LSD, cannabis, crack and amphetamines (speed)

Question 21

What are the positive symptoms of Schizophrenia?

Answer 21

• Delusions
• Hallucinations
• Thought disorder
• Abnormal, disorganised behaviour

Question 22

What are the negative symptoms Schizophrenia?

Answer 22

• Withdrawal from social contacts
• Flattening of emotional responses
• Emotional responses out of context
• Reluctance to perform everyday task

Question 23

What brain abnormalities do patients with Schizophrenia have?

Answer 23

• 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

Question 24

How are Dopamine and Schizophrenia linked?

Answer 24

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

Question 25

Where are the Principle Dopaminergic Tracts located?

Answer 25

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

Question 25

Where are the Principle Dopaminergic Tracts located?

Answer 25

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

Question 26

How do conventional anti-psychotic drugs work?

Answer 26

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.

Question 27

How are conventional anti-psychotic drugs eliminated?

Answer 27

Eliminated by metabolism in the liver

Question 28

Examples of conventional antipsychotic drugs?

Answer 28

Chlorpromazine
Trifluoperazine
Perphenazine
Fluphenazine
Thioridazine
Haloperidol
Thiothixene
Mesoridazine
Loxapine
Molidone
Pimozide

Question 29

What are the adverse reactions for conventional anti-psychotic drugs?

Answer 29

• Drowsiness and cognitive impariment
• Hypothermia
• Reduced seizure threshold
• Hypersensitivity
• Weight gain
• GI disturbance
• Withdrawal symptoms
• Extrapyramidal effects

Question 30

What are extrapyramidal effects?

Answer 30

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

Question 31

What is mechanism for atypical antipsychotic drugs?

Answer 31

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

Question 32

Examples for atypical antipsychotic drugs?

Answer 32

Clozapine
Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole

Question 33

What atypical drug is more effective than conventional antipsychotic drugs?

Answer 33

Clozapine

Question 34

What are the adverse reactions of atypical antipsychotic?

Answer 34

• Agranulocytosis
• Hyperglycaemia
• Weight gain with clozapine and olnazapine
• Withdrawal symptoms

Question 35

Which Antipsychotics are first choice drugs?

Answer 35

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.

Question 36

What causes Epilepsy?

Answer 36

Epilepsy results from paroxysmal uncontrolled discharges of neurons within the CNS

Question 37

What happens during an epilepsy episode?

Answer 37

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

Question 38

What are the two classifications of Epilepsy?

Answer 38

• Partial (Focal) Seizures
• Generalized seizures

Question 39

What are the different types of Partial (focal) seizures?

Answer 39

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)

Question 40

What are the different types of generalized seizures, and what are the characteristics?

Answer 40

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

Question 41

What causes epilepsy?

Answer 41

Anything that causes injuries to the brain can cause seizures

Question 42

Describe how seizures develop?

Answer 42

1. 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

2. Abnormal electrical properties of the affected cells, causing sudden excessive and asynchronized neuronal firing
3. May have no obvious stimulus or may be due to trauma, hypoglycemia or infection

Question 43

Explain the movement of of ions in Epilepsy?

Answer 43

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.