DRUGS ACTING ON NERVOUS SYSTEM-PART II (BSc. NURSING)

 DRUGS ACTING ON NERVOUS SYSTEM

PREPARED BY MR. ABHIJIT DAS


ANALGESICS: NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

ANALGESIC:

An analgesic is a drug that relieves pain.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

NSAIDs are medications that reduce pain, inflammation, and fever by blocking certain enzymes in the body.

CLASSIFICATION OF NSAIDS:

A.   Nonselective COX inhibitors

1.     Salicylates: Aspirin.

2.     Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen.

3.     Anthranilic acid derivative: Mephenamic acid.

4.     Aryl-acetic acid derivatives: Diclofenac, Aceclofenac.

5.     Oxicam derivatives: Piroxicam, Tenoxicam.

6.     Pyrrolo-pyrrole derivative: Kitorolac.

7.     Indole derivative: Indomethacin.

8.     Pyrazolone derivatives: Phenylbutazone, oxyphenbutazone.

B.   Selective COX-2 inhibitors

Celecoxib, Parecoxib, Etoricoxib.

C.   Analgesic-antipyretics with poor anti-inflammatory action

1.     Paraaminophenol derivative: Paracetamol (Acetaminophen).

2.     Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone.

3.     Benzoxazocine: Nefopam

MECHANISM OF ACTION OF NSAIDS

The mechanism of action of  NSAIDs is the inhibition of the enzyme cyclooxygenase (COX).

In response to injury, Cyclooxygenase is required to convert arachidonic acid into thromboxanes (TXA2), Prostacyclins (PGI2), and Prostaglandins (PGE2



Thromboxane is responsible for platelet aggregation, prostacyclin is responsible for gastric protection  and prostaglandin is responsible for pain, fever and inflammation.

So, NSAIDs inhibit production of prostaglandins, a group of compounds that contribute to inflammatory response and are responsible for signs such as fever and pain.

ASPIRIN

Aspirin is acetylsalicylic acid. It is rapidly converted in the body to salicylic acid which is responsible for most of the actions. 

MOA:

Aspirin non-selectively inhibits COX enzyme that means aspirin inhibits both COX-1 and COX-2. So ultimately PGE2 biosynthesis is inhibited, which was responsible for pain, fever, and inflammation.


PHARMACOLOGICAL ACTIONS:

1.     Respiration

At anti-inflammatory doses, respiration is stimulated. Further rise in salicylate level causes respiratory depression which may lead to death due to respiratory failure.

2.     CVS (Cardio Vascular System)

Larger doses of aspirin cause direct vasodilation so Blood pressure may fall.

3.     GIT (Gastro Intestinal Tract)

Aspirin irritates gastric mucosa, causes nausea and vomiting.

Aspirin also causes acute ulcer and erosive gastritis.

4.     Blood

Aspirin reduces platelet aggregation and bleeding time is prolonged to nearly twice the normal value.

5.     Immunological effect

Aspirin inhibits antigen-antibody reaction.

ADVERSE EFFECTS:

1.     At analgesic dose aspirin causes nausea, vomiting, blood loss in stools, peptic ulcer etc.

2.     Skin rashes of various types.

3.     Bone marrow depression leading to anaemia.

4.     Hypersensitivity reactions

5.     Dizziness

THERAPEUTICAL USES:

1.     As analgesic for headache, backache, joint pain, tooth ache etc.

2.     As antipyretic against fever of any origin. Paracetamol, being safer, is generally preferred.

3.     Used in Rheumatoid arthritis.

4.     Used in post myocardial infraction patients by inhibiting platelet aggregation.

CONTRAINDICATIONS:

1.     Allergy or hypersensitivity to aspirin or other NSAIDs.

2.     Active peptic ulcer disease or a history of gastrointestinal bleeding.

3.     Severe liver or kidney disease.

4.     Bleeding disorders or a tendency towards bleeding.

DOSE AND ROUTE:

1.     For pain relief or fever reduction:

·         Adult dose: 325-650 mg every 4 to 6 hours as needed.

·         Maximum daily dose: 4 grams.

2.     For antiplatelet therapy (prevention of heart attack or stroke):

·         Adult dose: 75-325 mg once daily.

Aspirin is commonly administered orally (ROUTE).

ROLE OF NURSE:

1.     Assessment: Nurses assess the patient's medical history, allergies, and current medications to determine if aspirin is appropriate for the patient's condition.

2.     Administration: Nurses administer aspirin according to the prescribed dosage, route, and schedule, ensuring patient safety and adherence to protocols.

3.     Monitoring: Nurses monitor patients for adverse reactions to aspirin, such as gastrointestinal bleeding or allergic reactions, and intervene promptly if necessary.

4.     Documentation: Nurses maintain accurate records of aspirin administration, including dosage, route, patient response, and any adverse events

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OPIOID ANALGESICS

Opioid analgesics are drugs primarily used to relieve pain. They work by binding to opioid receptors in the brain, spinal cord, and other areas of the body, reducing the perception of pain.

  • Opium: Opium is a natural substance derived from the sap of the opium poppy plant (Papaver somniferum). It contains various alkaloids, including morphine and codeine, which have pain-relieving properties.

·         Opioids: Opioids are substances that includes natural, semi-synthetic, and synthetic drugs that act on the body's opioid receptors. They can be derived from opium (like morphine and codeine), semi-synthesized from opium alkaloids (like heroin), or entirely synthetic (like fentanyl and pethidine).

CLASSIFICATION

1.     Natural opioids: Morphine, Codeine

2.     Semi-synthetic opioids: Oxycodone, Hydrocodone, Heroin

3.     Synthetic opioids: Fentanyl, Methadone, Pethidine

MORPHINE

MOA:

Morphine's mechanism of action involves blocking calcium channels on presynaptic neurons, which in turn blocks the release of neurotransmitters such as substance P.

Additionally, morphine opens potassium ion channels on postsynaptic neurons, leading to repolarization (no depolarization) and preventing further signal transmission.


PHARMACOLOGICAL ACTIONS:

1.     Central Nervous System (CNS):

·         Reduces visceral pain

·         Induces drowsiness

·         May produce a pleasurable floating sensation

2.     Respiration:

·         Depresses the respiratory center

·         Overdose can lead to respiratory depression, morphine poisoning, and potentially death

3.     Cardiovascular System:

·         Causes vasodilation

·         Reduces blood pressure (BP)

·         May result in bradycardia (slow heart rate)

·         Reduces cardiac work

4.     Gastrointestinal Tract (GIT):

·         Reduces gastrointestinal motility

·         Reduces gastrointestinal secretion

5.     Smooth Muscle:

·         Can cause bronchoconstriction (contraction of bronchial smooth muscle)

·         Induces contraction of the urinary bladder

ADVERSE EFFECTS:

1.     Respiratory depression, which can lead to death in cases of morphine overdose.

2.     Mental confusion and sedation.

3.     Hypotension (low blood pressure).

4.     Development of tolerance and dependence with prolonged use.

5.     Allergic reactions, though these are relatively rare, they can include symptoms such as rash, itching, and difficulty breathing.

THERAPEUTIC USES:

1.     Analgesics: Used for moderate to severe pain relief.

2.     Preanesthetics: Can alleviate anxiety and provide pain relief before anesthesia.

3.     Antitussive agents: Used to suppress severe coughing.

4.     Treatment of diarrhea: Sometimes used for severe cases when other medications fail.

CONTRAINDICATIONS:

1.     Respiratory depression: Patients with compromised respiratory function, such as severe asthma or chronic obstructive pulmonary disease (COPD).

2.     Acute or severe bronchial asthma: Morphine can worsen respiratory function in these patients.

DOSE AND ROUTE:

The typical dose of morphine ranges from 5 to 30 milligrams, administered orally or via injection (IV, IM & SC), every 4 hours as needed for pain relief.

ROLE OF NURSE:

1.     Assessment: Nurses evaluate pain level, vital signs, medical history, and allergies before giving morphine.

2.     Education: Nurses inform patients and families about morphine's purpose, dosage, side effects, and safety.

3.     Administration: Nurses give morphine as prescribed, following safety guidelines.

4.     Monitoring: Nurses watch for adverse reactions like respiratory depression or allergic responses and act swiftly if needed.

5.     Documentation: Nurses keep detailed records of morphine use, including dosage, patient response, and any issues.


DRUGS FOR NEURODEGENERATIVE DISORDERS

NEURODEGENERATIVE DISORDERS

Neurodegenerative disorders are conditions characterized by progressive damage to the nervous system, leading to the worsening of neurons (nerve cells) and ultimately impairing their functions.

Examples include Parkinson's disease & Alzheimer's disease.

Alzheimer's disease: progressive memory loss and cognitive decline.

Parkinson's disease: movement difficulties due to dopamine neuron degeneration.

DRUGS FOR PARKINSON’S DISEASE

  1. Dopaminergic agents: Levodopa/carbidopa, dopamine agonists
  2. MAO-B inhibitors: Selegiline, rasagiline
  3. COMT inhibitors: Entacapone, tolcapone
  4. Anticholinergic drugs: Benztropine, trihexyphenidyl

DOPAMINERGIC AGENTS

MOA:

Levodopa (L-DOPA): Turns into dopamine, boosting dopamine levels in the brain to alleviate Parkinson's symptoms.

Carbidopa: Blocks an enzyme dopamine decarboxylase that breaks down levodopa outside the brain, allowing more levodopa to reach the brain and convert into dopamine, enhancing its effectiveness in treating Parkinson's disease.


ADVERSE EFFECTS:

  • Levodopa/carbidopa: Nausea, dyskinesias (involuntary movements), fluctuations in motor response.

USES:

  • Levodopa/carbidopa: treatment for Parkinson's disease to alleviate motor symptoms.

DOSE AND ROUTE:

Levodopa and carbidopa are usually taken orally, with the typical starting dose of levodopa being around 100 mg, gradually increasing to 200 mg or more per tablet. Carbidopa is combined with levodopa at a ratio of 1:4, often at a dose of 25 mg carbidopa per 100 mg levodopa.

CONTRAINDICATIONS:

Common contraindications for levodopa and carbidopa therapy include:

1.     Hypersensitivity: Patients with a known hypersensitivity to levodopa, carbidopa, or any of the components of the formulation should avoid its use.

2.     Non-selective monoamine oxidase (MAO) inhibitors: Concurrent use of levodopa/carbidopa with non-selective MAO inhibitors is contraindicated due to the risk of hypertensive crisis.

ROLE OF NURSE:

1.     Patient education on medication administration and potential side effects.

2.     Monitoring for therapeutic response and adverse reactions.

3.     Providing emotional support and encouragement.

 

COMT INHIBITORS

MOA:

These drugs inhibit the enzyme COMT (catechol-O-methyltransferase), which normally breaks down levodopa in the bloodstream. By inhibiting COMT, these medications increase the availability of levodopa in the brain, enhancing its effectiveness in managing Parkinson's symptoms.


ADVERSE EFFECTS:

1.     Nausea

2.     Dyskinesias: Dyskinesias are unintentional and irregular movements

3.     Orthostatic hypotension: Some individuals may experience a drop in blood pressure upon standing (orthostatic hypotension)

USES:

1.     Enhance effectiveness of levodopa therapy.Top of Form

2.     Treatment of Parkinson’s disease

DOSE AND ROUTE:

Entacapone: Typically administered orally, with a usual dose of 200 mg taken with each levodopa/carbidopa dose, up to a maximum of 8 doses per day.

CONTRAINDICATIONS:

Contraindications for COMT inhibitors:

1.     Hypersensitivity to the medication.

2.     Concurrent use with non-selective MAO inhibitors.

ROLE OF NURSE:

The role of a nurse in the context of patients taking medications like COMT inhibitors involves:

1.     Educating patients on medication use.

2.     Monitoring for effects and side effects.

3.     Providing support and addressing concerns.

4.     Collaborating with the healthcare team.

 

MAO-B INHIBITORS

MOA:

Monoamine oxidase-B (MAO-B) inhibitors act by selectively inhibiting the enzyme monoamine oxidase type B, which is responsible for the breakdown of dopamine in the brain. By blocking this enzyme, MAO-B inhibitors prevent the degradation of dopamine, thereby increasing its availability.


ADVERSE EFFECTS:

1.     Gastrointestinal disturbances: Including nausea, vomiting, and diarrhea.

2.     Insomnia: Difficulty falling asleep or staying asleep.

3.     Hypotension: A sudden drop in blood pressure, leading to dizziness or lightheadedness.

USES:

1.     Management of Parkinson's disease: MAO-B inhibitors are used as adjunctive therapy to levodopa/carbidopa or dopamine agonists to improve motor symptoms and overall function in Parkinson's disease patients.

2.     Delaying disease progression: Some evidence suggests that MAO-B inhibitors may have neuroprotective effects, potentially slowing the progression of Parkinson's disease.

DOSE AND ROUTE:

Rasagiline: Typically administered orally, with a usual dose of 1 mg once daily

CONTRAINDICATIONS:

Common contraindications for MAO-B (monoamine oxidase-B) inhibitors include:

1.     Hypersensitivity: Patients with a known hypersensitivity to MAO-B inhibitors or any of the components of the medication should avoid its use.

2.     Concurrent use with other MAO inhibitors: MAO-B inhibitors should not be used concurrently with non-selective MAO inhibitors (e.g., phenelzine, tranylcypromine) due to the risk of hypertensive crisis.

ROLE OF NURSE:

In the context of patients taking medications like MAO-B inhibitors, the role of a nurse involves:

1.     Guiding patients on medication administration and potential side effects.

2.     Observing and documenting treatment responses and adverse reactions.

3.     Offering guidance and addressing patient queries or worries.

4.     Cooperating with healthcare peers to ensure comprehensive patient care.


DRUGS FOR ALZHEIMER’S DISEASE

1.     NMDA Receptor Antagonist: Memantine

2.     Cholinesterase Inhibitors: Donepezil, Galantamine, Rivastigmine, Tacrine

MEMANTIDINE

MOA:

Memantine blocks NMDA receptors, preventing excessive calcium influx into neurons and reducing excitotoxicity caused by glutamate, thus protecting neurons from damage.


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ADVERSE EFFECTS:

1.     Dizziness

2.     Headache

3.     Confusion

USES:

1.     Alzheimer's disease

2.     Vascular dementia (Vascular dementia is a type of dementia that occurs when impaired blood flow to the brain leads to cognitive decline)

DOSE AND ROUTE:

Memantine (oral tablets): The usual starting dose is 5 mg once daily, with gradual titration over several weeks to a target maintenance dose of 10 mg twice daily (20 mg/day)

CONTRAINDICATIONS:

1.     Hypersensitivity to memantine or its components.

2.     Severe renal impairment.

3.     Concurrent use with other NMDA receptor antagonists.

ROLE OF NURSE:

1.     Educating patients on medication use.

2.     Monitoring for effects and side effects.

3.     Collaborating with the healthcare team.

CHOLINESTERASE INHIBITORS

MOA:

·        Block Enzyme: Cholinesterase inhibitors (ChEIs) block the enzyme acetylcholinesterase (AChE).

·        Increase Acetylcholine: This prevents the breakdown of acetylcholine

·        Boost Communication: Higher acetylcholine levels improve communication between brain cells.

·        Enhance Memory and Cognition: This helps improve memory and cognitive functions in Alzheimer's patients.

ADVERSE EFFECTS:

1. Nausea

2. Diarrhea

3. Muscle cramps

USES:

1.     Alzheimer's disease

2.     Myasthenia gravis

DOSE AND ROUTE:

1.     Donepezil:

·         Dose: 5-10 mg once daily (initial), can be increased to 23 mg once daily

·         Route: Oral

2.     Rivastigmine:

·         Dose: 1.5-6 mg twice daily (oral), or 4.6-13.3 mg/24 hours (transdermal patch)

·         Route: Oral, Transdermal

3.     Galantamine:

·         Dose: 4-12 mg twice daily (immediate-release), or 8-24 mg once daily (extended-release)

·         Route: Oral

CONTRAINDICATIONS:

Contraindications of Cholinesterase Inhibitors

1.     Bradycardia

2.     Peptic ulcer disease

3.     Asthma or chronic obstructive pulmonary disease (COPD)

4.     Urinary tract obstruction

ROLE OF NURSE:

1.     Administer Medication: Give cholinesterase inhibitors as prescribed.

2.     Educate Patients: Explain medication purpose, dosage, and potential side effects.

3.     Monitor Patients: Track their response to treatment and any adverse reactions.

4.     Collaborate with Team: Work with other healthcare professionals for coordinated care.

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