Drugs act on central nervous system

Learning objectives: Learn about the drugs that act on central nervous system, their classification and mechanism of action

Sympathetic vs Parasympathetic nervous system  

Autonomic Nervous System (ANS)

• Controls involuntary body functions like heart rate, digestion, respiration, and gland activity.

• The Autonomic Nervous System (ANS) is divided into two main divisions that work in opposition to maintain body balance (homeostasis).:

1. Sympathetic nervous system (SNS) – “fight or flight”

2. Parasympathetic nervous system (PNS) – “rest and digest”

1. Sympathetic Nervous System (SNS)

• Function: Prepares the body for stressful or emergency situations.

• Origin: Thoracolumbar region of the spinal cord (T1–L2).

• Main neurotransmitters: Acetylcholine (preganglionic), Norepinephrine (postganglionic).

• Key effects:

• Increases heart rate and force of contraction

• Dilates bronchi to improve breathing (bronchodilation)

• Constricts blood vessels in the skin and gut

• Increase blood pressure

• Dilates pupils (mydriasis)

• Reduces gastrointestinal motility and secretions, thereby, digestion and intestinal activity

 • Urinary retention

• Stimulates sweat glands

• Adrenal medulla releases adrenaline for rapid response

 • Increase Blood glucose (glycogenolysis, gluconeogenesis)

  • Ejaculation

Neurotransmitters for Sympathetic Nervous System (SNS)

• Preganglionic: Acetylcholine (ACh)

• Postganglionic: Noradrenaline (Norepinephrine)

(Exception: sweat glands → ACh) 

2. Parasympathetic Nervous System (PNS)

• Function: Conserves energy and promotes relaxation, digestion, and repair.

• Origin: Cranial nerves (III, VII, IX, X) and sacral spinal cord (S2–S4).

• Main neurotransmitter: Acetylcholine (both pre- and postganglionic).

• Key effects:

• Slows heart rate

• Constricts bronchi

• Stimulates digestion and intestinal activity

• Constricts pupils and focuses the lens for near vision

• Promotes urination

• Stimulates salivation

Neurotransmitters for Parasympathetic Nervous System (PNS)

• Preganglionic: Acetylcholine (ACh)

• Postganglionic: Acetylcholine (ACh) [Memory trick: Acetylcholine (ACh) for both in Parasympathetic Nervous System]

• Sympathetic NS→ Emergency  = fight or flight → prepares for action

• Parasympathetic NS→ Peace  = rest and digest → conserves energy and restores body function

Epilepsy

Epilepsy is a common chronic neurological disorder that is characterized by recurrent unprovoked seizures.

Epilepsy is a brain disorder in which clusters of nerve cells, or neurons, in the brain sometimes signal abnormally. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and behaviour or sometimes convulsions, muscle spasms, and loss of consciousness. Epilepsy is a disorder with many possible causes. Anything that disturbs the normal pattern of neuron activity - from illness to brain damage to abnormal brain development - can lead to seizures. Epilepsy may develop because of an abnormality in brain wiring, an imbalance of nerve signalling chemicals called neurotransmitters, or some combination of these factors. Having a seizure does not necessarily mean that a person has epilepsy. Only when a person has had two or more seizures is he or she considered having epilepsy. EEGs and brain scans are common diagnostic test for epilepsy.

Epilepsy is a condition in which a person has recurrent seizures. A seizure is defined as an abnormal, disorderly discharging of the brain's nerve cells, resulting in a temporary disturbance of motor, sensory, or mental function.

There are many types of seizures, depending primarily on what part of the brain is involved. The term epilepsy says nothing about the type of seizure or cause of the seizure, only that the seizures happen again and again. A stricter definition of the term requires that the seizures have no known underlying cause. This may also be called primary or idiopathic epilepsy.

Episodes of abnormal electrical activity within the brain result in seizures.

The specific area of the brain affected by the abnormal electrical activity may result in a particular type of seizure.

If all areas of the brain are affected by the abnormal electrical activity, a generalized seizure may result. This means that consciousness is lost or impaired. Often all the person's arms and legs stiffen and then jerk rhythmically.

One seizure type may evolve into another during the course of the seizure. For example, a seizure may start as a partial, or focal, seizure, involving the face or arm. Then the muscular activity spreads to other areas of the body. In this way, the seizure becomes generalized.

Seizures caused by high fevers in children are not considered epilepsy. Also see children’s seizures.

Cause of Epilepsy:

It is estimated to affect one percent of the U.S. population, about 2.5 million people.

In about half of all cases no cause can be found, but

• head injuries,

• brain tumors,

• lead poisoning,

• problems in brain development before birth, and

• certain genetic and infectious illnesses can all cause epilepsy.

Epilepsy occurs when nerve cells in the brain fire electrical impulses at a rate of up to four times higher than normal. This causes a sort of electrical storm in the brain, known as a seizure. A pattern of repeated seizure is referred to as epilepsy. Medication controls seizure for the majority of patients, who are otherwise healthy and able to live full and productive lives.

Basic research aims to identify viral, genetic, or other factors that cause epilepsy. These findings provide the basis for developing new and improved methods of prevention and therapy.

Is there any treatment?

Once epilepsy is diagnosed, it is important to begin treatment as soon as possible. For about 80 percent of those diagnosed with epilepsy, seizures can be controlled with modern medicines and surgical techniques. Some antiepiletic drugs can interfere with the effectiveness of oral contraceptives. In 1997, the FDA approved the vagus nerve stimulator for use in people with seizures that are not well-controlled by medication.

What is the prognosis?

Most people with epilepsy lead outwardly normal lives. While epilepsy cannot currently be cured, for some people it does eventually go away. Most seizures do not cause brain damage. It is not uncommon for people with epilepsy, especially children, to develop behavioral and emotional problems, sometimes the consequence of embarrassment and frustration or bullying, teasing, or avoidance in school and other social setting. For many people with epilepsy, the risk of seizures restricts their independence (some states refuse drivers licenses to people with epilepsy) and recreational activities. People with epilepsy are at special risk for two life-threatening conditions: status epilepticus and sudden unexplained death. Most women with epilepsy can become pregnant, but they should discuss their epilepsy and the medications they are taking with their doctors. Women with epilepsy have a 90 percent or better chance of having a normal, healthy baby.

What research is being done?

Scientists are studying potential antiepileptic drugs with goal of enhancing treatment for epilepsy. Scientists continue to study how neurotransmitters interact with brain cells to control nerve firing and how non-neuronal cells in the brain contribute to seizures. One of the most-studied neurotransmitters is GABA, or gamma-aminobutryic acid. Researchers are working to identify genes that may influence epilepsy. This information may allow doctors to prevent epilepsy or to predict which treatments will be most beneficial. Doctors are now experimenting with several new types of therapies for epilepsy, including transplanting fetal pig neurons into the brains of patients to learn whether cell transplants can help control seizures, transplanting stem cells, and using a device that could predict seizures up to 3 minutes before they begin. Researchers are continually improving MRI and other brain scans. Studies have show that in some case, children may experience fewer seizures if they maintain a strict diet - called the ketogenic diet - rich in fats and low in carbohydrates.

Partial Seizures

Partial seizures are divided into simple, complex and those that evolve into secondary generalized seizures.

Simple partial seizures are further subdivided into four categories according to the nature of their symptoms: motor, autonomic, sensory or psychological.

 Motor symptoms include -

movements such as jerking and stiffening.

Sensory symptoms caused by seizures involve unusual sensations affecting any of the five senses (vision, hearing, smell, taste or touch). When simple partial seizures cause sensory symptoms only (and not motor symptoms), they are called "auras."

Autonomic symptoms affect the autonomic nervous system, which is the group of nerves that control the functions of our organs, like the heart, stomach, bladder, intestines. Therefore autonomic symptoms are things like racing heart beat, stomach upset, diarrhea, loss of bladder control.

The only common autonomic symptom is a peculiar sensation in the stomach that is experienced by some patients with a type of epilepsy called temporal lobe epilepsy. Simple partial seizures with psychological symptoms are characterized by various experiences involving memory (the sensation of deja-vu), emotions (such as fear or pleasure), or other complex psychological phenomena.

Complex partial seizures, by definition, include impairment of awareness. Patients seem to be "out of touch," "out of it" or "staring into space" during these seizures. There may also be some "complex" symptoms called automatisms. Automatisms consist of involuntary but coordinated movements that tend to be purposeless and repetitive. Common automatisms include lip smacking, chewing, fidgeting and walking.

The third kind of partial seizure is one that begins as a focal seizure and evolves into a generalized convulsive ("grand-mal") seizure.

Most patients with partial seizures have simple partial, complex partial and secondarily generalized seizures. In about two-thirds of patients with partial epilepsy, seizures can be controlled with medications. Partial seizures that cannot be treated with medications can often be treated surgically.

Classification of Epilepsy:

A. Generalized seizure:

1. Generalized clonic- tonic seizure/ Grand mal/ Major Epilepsy:

- Commonest epilepsy

- Lasts 1-2 mins

- The usual sequence is aura-cry

- Unconsciousness

- Tonic spasm of all body muscles

- Clonic jerking followed by prolonged sleep and depression of all CNS functions.

2. Absence seizure/ Petit mal/ Minor Epilepsy:

- Prevalent in children

- Lasts about 1-2 minutes

- Momentary loss of consciousness.

- Patients apparently freezes and stares in one direction

- No muscular component or little bilateral jerking

- EEG shows characteristic 3 cycle per second spike and wave pattern.

3. Atonic seizure/ Akinetic epilepsy:

- Unconsciousness with relaxation of all muscles due to excessive inability discharge.

- Patient may fall.

4. Myoclonic seizure:

- Shock like momentary contraction of muscles of a limb or the whole body.

5. Infantile spasm/ Hypsarhythmia

- Seen in infants

- Probably not a form of epilepsy

- Intermittent muscle spasm and progressive mental deterioration

- Diffuse changes in the inter-seizure EEG are noted.

B. Partial Seizures

Partial seizures are divided into simple, complex and those that evolve into secondary generalized seizures.

1. Simple partial seizure/ Cortical focal epilepsy:

- Lasts 0.5-1 min

- Convulsions are confined to a group of muscle or localized sensory disturbance depending on the area of cortex involved in the seizure, without loss of consciousness.

2. Complex partial seizure/ Temporal lobe epilepsy/ Psychomotor:

-        Attacks of bizarre and confused behaviour

-        Purposeless movement

-        Emotional change lasting 1-2 min along with impairment of consciousness

-        An aura proceeds

-        The seizure focus is located in the temporal lobe.

3. Simple partial or complex partial seizures secondarily generalised:

- The partial seizure occurs first and evolves into generalised tonic-clonic  seizures with loss of consciousness.

International Classification of Epilepsies and Epileptic Syndromes 1

1. Localization-related (focal, local, partial) epilepsies and syndromes

1.1. Idiopathic with age-related onset

A. Benign childhood epilepsy with centrotemporal spikes

B. Childhood epilepsy with occipital paroxysms

1.2. Symptomatic

2. Generalized epilepsies and syndromes

2.1. Idiopathic, with age-related onset (listed in order of age)

A. Benign neonatal familial convulsions

B. Benign neonatal convulsions

C. Benign myoclonic epilepsy in infancy

D. Childhood absence epilepsy (pyknolepsy)

E. Juvenile absence epilepsy

F. Juvenile myoclonic epilepsy (impulsive petit mal)

G. Epilepsy with grand mal seizures on awakening

2.2. Idiopathic and/or symptomatic (listed in order of age)

A. West syndrome (infantile spasms)

B. Lennox-Gastaut syndrome

C. Epilepsy with myoclonic-astatic seizures

D. Epilepsy with myoclonic absences

2.3. Symptomatic

A. Nonspecific etiology

a. Early myoclonic encephalopathy

B. Specific etiology

a. Epileptic seizures may complicate many disease states

3. Epilepsies and syndromes undetermined as to whether they are focal or generalized

3.1. With both generalized and focal seizures

A. Neonatal seizures

B. Severe myoclonic epilepsy in infancy

C. Epilepsy with continuous spike waves during slow-wave sleep

D. Acquired epileptic aphasia (Landau-Kleffner syndrome)

3.2. Without unequivocal generalized or focal features

4. Special syndromes

4.1. Situation-related seizures

A. Febrile convulsions

B. Seizures related to other identifiable situations such as stress, hormonal changes, drugs, alcohol, or sleep deprivation

4.2. Isolated, apparently unprovoked epileptic events

4.3. Epilepsies characterized by specific modes of seizure precipitation

Symptoms of Epilepsy

The following symptoms may indicate someone has epilepsy. A medical exam is advised if one or more of these symptoms are present. The symptoms include:

• A convulsion with or without a fever

• Short periods of blackout or confused memory

• Occasional "fainting spells" in which bladder or bowel control is lost, followed by extreme fatigue

• Episodes of blank staring

• Brief periods of no response to questions or instructions

• Sudden stiffening or falls for no apparent reason

• Episodes of blinking or chewing at inappropriate times

• Dazed behavior; being unable to talk or communicate for a short time

• Repeated movements that look out of place or unnatural

• Sudden fear, anger or panic for no reason

• Odd changes in the way things look, sound, smell or feel

• Muscle jerks of arms, legs or body

• Clusters of swift jerking movements in babies

Conditions that may be mistaken for epilepsy:

• Seizures associated with high fever

• Fainting

• Sleep disorders: nightmares, narcolepsy, cataplexy

• Psychiatric disorders: panic attacks, fugue states, psychogenic seizures

• Transient ischemic attacks (TIAs): brief interruptions of blood flow to the brain

• Migraine headaches

• Childhood breath-holding episodes 

Practice questions

Further reading

• Antibiotic Classes in 7 minutes

• A Brief Overview of Classes of Antibiotics

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