Nervous System

Ass. 1
Ass.2

1.

a.Sympathomimetic drugs

MOA and indication

The mechanisms of sympathomimetic drugs can be direct-acting (direct interaction between drug and
receptor), such as α-adrenergic agonists, β-adrenergic agonists, and dopaminergic agonists; or indirect-
acting (interaction not between drug and receptor), such as MAOIs, COMT inhibitors, release stimulants,
and reuptake inhibitors that increase the levels of endogenous catecholamines.

The clinical indications for sympathomimetics are broad and include asthma, heart failure, shock, and anaphylaxis.
Side effects include hypertension, sinus tachycardia, and skeletal muscle tremor.
b.Sympatholytic Drugs

Antiadrenergic agents inhibit the signals of epinephrine and norepinephrine. They are primarily postsynaptic
adrenergic receptor antagonists (alpha and beta adrenergic receptor antagonists, or "blockers"), inhibiting the
downstream cellular signaling pathways of adrenergic receptors.

They may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder,
panic disorder and PTSD.

2.

a.Parasympathomimetic drugs

 Mechanism of action
 Direct parasympathomimetics: bind to muscarinic or nicotinic ACh receptors
 Indirect parasympathomimetics: inhibit acetylcholine esterase 

 Mechanism of Action
 Direct-acting parasympathomimetic agents act at muscarinic ACh receptors to mimic the
physiologic effects resulting from activation of the parasympathetic nervous system. All
muscarinic receptor subtypes (M1-M5) are G protein-coupled receptors linked to
intracellular signal transduction pathways. Binding of direct agonists to Gq-coupled M1,
M3, and M5 receptor subtypes stimulates phospholipase C, which initiates the
phosphatidylinositol signaling cascade, ultimately leading to the mobilization of
intracellular calcium and activation of protein kinase C. Binding of direct agonists to
Gi/o-coupled M2 and M4 receptor subtypes leads to inhibition of adenylyl cyclase
activity, resulting in decreased levels of cyclic AMP, and to increased potassium
conductance, resulting in hyperpolarization of the membrane potential.[7][8]
 The five subtypes of muscarinic ACh receptors have varying distributions throughout the
central nervous system and periphery. For example, M1 receptors are mainly found in
cortical regions of the brain, autonomic ganglia, glands (gastric and salivary), and enteric
nerves. M2 receptors are predominantly expressed in cardiac and smooth muscle. M3
receptors are abundant in exocrine glands, smooth muscle, and vascular endothelium.[9]
 The parasympathomimetic effects of indirect-acting agents are mediated by their
inhibitory effect on the hydrolysis of endogenous ACh at cholinergic synapses by
acetylcholinesterase. Increased synaptic concentrations of ACh results in prolonged
stimulation of cholinergic receptors throughout the central and peripheral nervous
systems.[10]

The significant effects of parasympathomimetic medications are summarized below by organ

system:
 Eye
o Contraction of the sphincter pupillae muscle (miosis)
 o Contraction of the ciliary muscle (accommodation for near vision)
 Cardiovascular
o Vasodilation (via endothelium-derived relaxing factor)
o Decrease in firing rate of the sinoatrial node (negative chronotropy)
o Decrease in conduction velocity through the atrioventricular node (negative
dromotropy)
o Decrease in contractile strength of the atria (negative inotropy)
 Gastrointestinal
o Stimulation of salivary and gastric glands
o Increase in gut motility
o Relaxation of sphincters
 Urinary
o Contraction of the detrusor muscle
o Relaxation of the trigone and sphincter muscles
 Respiratory
o Contraction of bronchial smooth muscle
o Stimulation of tracheobronchial secretions
 Other Effects
o Stimulation of secretion from lacrimal, sweat, and nasopharyngeal glands
Mechanism of Action
 a. G –protein linked (Muscarinic), through transmembrane 2nd messenger signaling
 b. Ligand gated Ion channels (Nicotinic)
 Muscarinic receptors act through DAG/IP3 second messenger system.

Indications

Drug Indications

Direct parasympathomimetics (direct agonist)

Bethanechol Postoperative
and neurogenic ileus and urinary retention
 Drug Indications

Direct parasympathomimetics (direct agonist)

Carbachol Alleviation of intraocular pressure

Miosis

Pilocarpine Induces sweat, tears, and saliva

production
Open-angle and closed-angle glaucoma

Methacholine Diagnosis of bronchial hypersensitivity →

See bronchial challenge test.

Indirect parasympathomimetics (indirect agonist)

Neostigmine Postoperative ileus and urinary retention 

Myasthenia gravis
Postoperative reversal of neuromuscular
blockade

Pyridostigmine Myasthenia gravis

Edrophonium Used to diagnose myasthenia gravis in

the past 

Physostigmine  Glaucoma
Antidote for atropine overdose

Donepezil Alzheimer's disease

Rivastigmine

Galantamine
Or

Direct-Acting Parasympathomimetics
 Bethanechol: Urinary retention, postoperative and neurogenic ileus
 Carbachol: Induction of miosis, open-angle glaucoma
  Cevimeline: Xerostomia (especially in Sjögren syndrome)[1]
 Methacholine: Challenge test to assess airway hyperresponsiveness in the clinical
diagnosis of asthma
 Pilocarpine: Induction of sweating, lacrimation, and salivation, open-angle and closed-
angle glaucoma
Indirect-Acting Parasympathomimetics
 Donepezil, Rivastigmine, and Galantamine: Alzheimer diseases
 Edrophonium: Historically used in the diagnosis of myasthenia gravis
 Neostigmine: Postoperative and neurogenic ileus and urinary retention, myasthenia
gravis, postoperative reversal of neuromuscular blockade
 Physostigmine: Antidote for anticholinergic toxicity
 Pyridostigmine: Myasthenia gravis
b.Anticholinergic Drugs

Anticholinergic drugs competitively inhibit binding of the neurotramsmitter, acetylcholine. They target

either muscuranic acetylcholine receptors or, less commonly, nicotinic acetylcholine receptors.

Anticholinergics are used to treat a variety of conditions. These include:

 Muscuranic receptors are found on nerve endings to smooth muscles cells, secretory glands and the eye.
They are also found in the central nervous system.
 Nicotinic acetylcholine receptors are located at the nerve endings of neuromuscular junctions and are the
target of muscle relaxing drugs.
 chronic obstructive pulmonary disease (COPD)

 overactive bladder and incontinence

 gastrointestinal disorders, such as diarrhea

 asthma

 dizziness and motion sickness

 poisoning caused by toxins such as organophosphates or muscarine, which may be found in some
insecticides and poisonous mushrooms

 symptoms of Parkinson’s disease, such as abnormal involuntary muscle movement

Ass.3

1. Parkinson’s Disease

Parkinson's disease is a progressive nervous system disorder that affects movement. Symptoms start
gradually, sometimes starting with a barely noticeable tremor in just one hand. Tremors are common, but the
disorder also commonly causes stiffness or slowing of movement.

The pathophysiology of Parkinson's disease is death of dopaminergic neurons as a result of changes in

biological activity in the brain with respect to Parkinson's disease (PD). There are several proposed mechanisms
for neuronal death in PD; however, not all of them are well understood. Five proposed major mechanisms for
neuronal death in Parkinson's Disease include protein aggregation in Lewy bodies, disruption of autophagy, changes
in cell metabolism or mitochondrial function, neuroinflammation, and blood-brain barrier (BBB) breakdown resulting in
vascular leakiness.

2. Schizophrenia

Schizophrenia is a chronic, severe mental disorder that affects the way a person thinks, acts, expresses
emotions, perceives reality, and relates to others. Though schizophrenia isn’t as common as other major mental
illnesses, it can be the most chronic and disabling.

3. Alzheimer’s Disease

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking
skills and, eventually, the ability to carry out the simplest tasks. In most people with the disease—those with
the late-onset type—symptoms first appear in their mid-60s. Early-onset Alzheimer’s occurs between a person’s
 30s and mid-60s and is very rare. Alzheimer’s disease is the most common cause of dementia among older
adults.

Pathophysiology

The 2 pathologic hallmarks of Alzheimer disease are

 Extracellular beta-amyloid deposits (in senile plaques)

 Intracellular neurofibrillary tangles (paired helical filaments)

The beta-amyloid deposition and neurofibrillary tangles lead to loss of synapses and neurons, which results in
gross atrophy of the affected areas of the brain, typically starting at the mesial temporal lobe.

The mechanism by which beta-amyloid peptide and neurofibrillary tangles cause such damage is incompletely
understood. There are several theories.

The amyloid hypothesis posits that progressive accumulation of beta-amyloid in the brain triggers a complex
cascade of events ending in neuronal cell death, loss of neuronal synapses, and progressive neurotransmitter
deficits; all of these effects contribute to the clinical symptoms of dementia.
Prion mechanisms have been identified in Alzheimer disease. In prion diseases, a normal cell-surface brain
protein called prion protein becomes misfolded into a pathogenic form termed a prion. The prion then causes other
prion proteins to misfold similarly, resulting in a marked increase in the abnormal proteins, which leads to brain
damage. In Alzheimer disease, it is thought that the beta-amyloid in cerebral amyloid deposits and tau in
neurofibrillary tangles have prion-like, self-replicating properties.

4.Seizure

A seizure is a sudden, uncontrolled electrical disturbance in the brain. It can cause changes in your
behavior, movements or feelings, and in levels of consciousness. If you have two or more seizures or a tendency to
have recurrent seizures, you have epilepsy.
5.Hydrocephalus

Hydrocephalus is an abnormal buildup of cerebrospinal fluid (CSF) in the ventricles of the brain. The fluid is
often under increased pressure and can compress and damage the brain.

6.Cerebral Palsy

Cerebral Palsy is considered a neurological disorder caused by a non-progressive brain injury or

malformation that occurs while the child’s brain is under development. Cerebral Palsy primarily affects body
movement and muscle coordination. Though Cerebral Palsy can be defined, having Cerebral Palsy does not
define the person that has the condition.

Cerebral palsy is caused by damage to the motor cortex of the brain. This is the part of the brain that affects
muscle control and coordination. CP treatments are always highly individualized to suit the needs of the patient.

7. Multiple Sclerosis

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system that
disrupts the flow of information within the brain, and between the brain and body.

Pathophysiology of multiple sclerosis. Multiple sclerosis is an inflammatory

demyelinating disease of the CNS in which activated immune cells invade the central
nervous system and cause inflammation, neurodegeneration, and tissue damage. The
underlying cause is currently unknown.
https://www.google.com/search?q=mechanism+of+action++
+of+sympathomimetic+drugs&hl=en&sxsrf=ALeKk00XZCgIjqL9sgxIyDgmskvfO1ehXA:1585809536586&s
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=1366&bih=635#imgrc=MGep41NbpIRvWM

https://www.healthline.com/health/anticholinergics

https://www.healthline.com/health/anticholinergics#uses

https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055

https://en.wikipedia.org/wiki/Pathophysiology_of_Parkinson%27s_disease

https://www.nia.nih.gov/health/what-alzheimers-disease

https://www.msdmanuals.com/professional/neurologic-disorders/delirium-and-dementia/alzheimer-
disease

https://www.mayoclinic.org/diseases-conditions/seizure/symptoms-causes/syc-20365711

https://www.emed.theclinics.com/article/S0733-8627(10)00074-X/pdf