Drugs used in neurodegenerative disorders

1. DRUGS FOR
NEUROGENERATIVE
DISORDER
By- kahkesha samshad.
M.pharm(1st year) pharmacology.
1600100558B

2. NEURODEGENERATIVE DISORDER
 Neurodegenerative disease is a conditions which primarily affect the neurons in the
human brain.
 Neurons are the building blocks of the nervous system Which includes the brain and
spinal cord
 Examples of neurodegenerative diseases include Parkinson’s, Alzheimer’s, etc
 Neurodegenerative diseases are incurable and debilitating conditions that result in
progressive degeneration or death of nerve cells
 This causes problems with movement (called ataxias), or mental functioning
(called dementias).
 Dementia, also known as senility, A Broad category of brain diseases that cause a
long term and often gradual decrease in the ability to think and remember. Great
enough to affect a person's daily functioning. Other common symptoms include
emotional problems, problems with language, and a decrease in motivation.

3. ALZHIEMER DISEASE
 Alzheimer’s disease is the most common form of dementia. It is a neurological brain
disorder named after a German physician, Alois Alzheimer, Who first described it in
1906.
 Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys
memory and thinking skills . Abnormal changes in the brain worsen over time.
 Memory loss is one of the earliest symptoms, along with a gradual decline of other
intellectual and thinking abilities, called cognitive functions, and changes in personality
or behaviour.
 Alzheimer's advances in stages, progressing from mild forgetfulness and cognitive
impairment to widespread loss of mental abilities . The time course of the disease varies
by individual, ranging from five to 20 years
 main symptoms of Alzheimer’s : Memory loss and confusion. Difficulty thinking and
understanding , Confusion in the evening hours , Delusion, disorientation, forgetfulness,
making things up, Mental confusion, difficulty concentrating, Inability to create new
memories , Inability to do simple maths, Inability to recognise common things

4. causes
 Alzheimer's disease causes loss of brain cells in areas of the brain. Some of the
deterioration may be related to a loss of chemical messengers in the brain,
called neurotransmitters acetylcholine That allow nerve cells in the brain to
communicate properly . People with Alzheimer's disease have two things in the
brain that are not normal: amyloid plaques and neurofibrillary tangles
 Amyloid plaques are clumps of a protein called beta amyloid ,this plaque builds
up around the cells in the brain that communicate with each other.
Neurofibrillary tangles are made from a protein called tau. Normally, the tau
protein helps cells communicate in the brain but In Alzheimer's disease, the tau
protein twists and tangles . The tangles clump together, and some nerve cells
die, which makes communication in the brain much harder.
 As brain cells die, it shrinks. The damage to the brain eventually causes
problems with memory, intelligence, judgment, language, and behaviour.

5.  Drug for Alzheimer’s Diseases •
 Donepezil (Aricept) is the only Alzheimer's drug approved to treat all stages
of the disease. ...
 Galantamine (Razadyne) is approved to treat mild to moderate Alzheimer's. .
 Rivastigmine (Exelon) is approved for mild to moderate Alzheimer's disease

6. Donepezil-
 sold as the trade name Aricept among others, is a medication used to
treat alzhiemer’s disease. It appears to result in a small benefit in mental function and
ability to function.
 Use, however, has not been shown to change the progression of the disease. Treatment
should be stopped if no benefit is seen.
 It is taken by mouth.
 Common side effects include nausea, trouble sleeping, aggression, diarrhoea, feeling
tired, and muscle cramps. Serious side effects may include abnormal heart rhythms,
frequent urge to urinate, and seizures.
 Donepezil is a centrally acting reversible acetylcholine esterase inhibitor and
structurally unrelated to other anticholinesterase agents.
 Donepezil and rivastigmine selectively inhibits cholinesterase in the CNS with less
effect on cholinesterase in peripheral tissues.
 These drugs can slow the deterioration of cognitive function.

7. PARKINSON’S DISEASE.
 Degenerative brain disorder affecting movement . It is caused by the deficiency
of a chemical in the brain called Dopamine
 Named after James Parkinson . Who published 'An Essay on the Shaking Palsy' in
1817, which established Parkinson’s as a recognised medical condition.
 the main symptoms of Parkinson’s Disease are Tremor: can occur at rest, in the
hands, limbs, or can be postural , Muscular: difficulty standing, Difficulty
walking, difficulty with bodily movements, Involuntary movements, muscle
rigidity, Problems with coordination, rhythmic muscle contractions, Slow bodily
movement,
 Parkinson's disease is caused by the progressive impairment or deterioration of
neurons (nerve cells) in an area of the brain known as the substantia nigra . When
functioning normally, these neurons produce a vital brain chemical known as
dopamine Dopamine serves as a chemical messenger allowing communication
between the substantia nigra and another area of the brain called the corpus
striatum. This communication coordinates smooth and balanced muscle
movement . A lack of dopamine results in abnormal nerve functioning, causing a
loss in the ability to control body movements

8. Classification.
1. Drug affecting brain dopaminergic system-
 Dopamine precursor- levodopa(L-dopa)
 Peripheral decarboxylase inhibitor- carbidopa, benserazide.
 Dopaminergic agonists- bromocriptine, ropinirole, pramipexole.
 MAO-B inhibitor- selegline, rasagline
 COMT inhibitors- entacapone, tolcapone
 Glutamate (NMDA receptor) antagonist(dopamine facilitator)- Amantadine
2. Drug affecting brain cholinergic system-
 Central anticholinergics- trihexyphenidyl(benzhexol), procyclidine, biperidem.
 Antihistaminics- orphenadrine, promethazine.

9. LEVODOPA(L-DOPA)
 Precursor of dopamine.
 It is inactive by itself, but it is immediate precursor of the transmitter dopamine.
 Both therapeutic and adverse effects result from the decarboxylation of levodopa to dopamine.
Pharmacological Actions.
 CNS- no effect on normal individual. Marked symptomatic improvement in parkinsonian
patients.
 CVS- cause tachycardia by acting on 𝛃 adrenergic receptor.
 CTZ- elicits nausea and vomiting.
 Endocrine- inhibits prolactin release to increase GH release.
PHARMACOKINETICS- it is rapidly absorbed orally from the small intestine by utilizing the active
transport process meant for aromatic amino acids.
 Bioavailability is affected by- gastric emptying.
ADVERSE EFFECTS- Nausea and vomiting, postural hypotension, cardiac arrhythmias,
exacerbation of angina, alteration in taste sensation.
After long therapy- abnormal movement(dyskinesia), behavioral effects, fluctuations in motor
performance.

10. CARBIDOPA AND BENSERAZIDE
 Carbidopa and benserazide are extracerebral dopa decarboxylase inhibitors. They do not
penetrate blood brain barrier and do not inhibit conversion of levodopa to dopamine in
the brain. Administration along with levodopa, they increase its t ½ in the periphery and
make more of it available to cross blood-brain barrier and reach its side of action.
 Levodopa is usually given in combination with carbidopa.
AMANTADINE-
 This drug is an antiviral agents that probably works by increasing the release and
inhibiting the reuptake of dopamine on nigrostriatal neurons.
 Adverse effect- it may cause livedo reticularis (a reddish blue mottling of the skin with
edema)
 It is used as a single agent in mild Parkinson’s disease or more often as an adjunct to
levodopa.

11. Amyotrophic lateral sclerosis(ALS)
 when the motor neurons eventually die, the ability of the brain to control
muscle movement is lost Causing paralysis of A progressive
neurodegenerative disease “is a condition in which cells of the brain and
spinal cord are lost.” This affects mostly motor neurons . The cells that
control needed voluntary muscle activity such as speaking, skeletal muscle
movement, breathing, and swallowing.
 essential body systems.
 Possible causes of ALS is- Oxidative stress.
 Drug for ALS –
 U.S. officials have approved only one drug that can help slow down ALS
 It’s called riluzole (Rilutek)
 It’s designed to reduce damage to your motor nerve cells by lowering the amount of a
substance called glutamate.
 It is available in tablet and liquid form.

12. SENIAL DIMENTIA
 Senile dementia is a disease caused by degeneration of the brain cells.
 senility, which is now more commonly referred to as senile dementia. Characterized
by a decrease in cognitive abilities. This may include the person’s ability to
concentrate, to recall information, and to properly judge a situation. Senility is a
deterioration of body and mind associated with advanced aging.
HUNGTINGTON’S DISEASE
 Huntington’s disease is an autosomal dominant hereditary disorder characterized by
choreiform movements and progressive mental impairment, usually beginning in
middle age.
 The pathogenesis of the disease is related to the degeneration of GABA neurons in
the striatum which leads to disinhibition of thalamic nuclei and to an increase of
thalamic input to the cortex.