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Drugs Acting On Central Nervous System

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  • Revised on: 2020-08-20

Drugs Acting On Central Nervous System is among the most commonly used drugs today.
To start with is an important class of drugs known as non-steroidal anti-inflammatory drugs.

Non-steroidal Ant-inflammatory Drugs (NSAIDS).

Analgesics are broadly classified into two categories:

  1. Opioid analgesics and
  2. Non-opioid analgesics

All drugs in this category have analgesic, antipyretic and anti-inflammatory actions in different measures. They are also known as non-narcotic, non-opioid or aspirin-like analgesics.

These drugs comprise of:

  1. Salicylates,
  2. paracetamol,
  3. Non selective COX inhibitor NSAIDS and,
  4. Selective COX2 inhibitor NSAIDS.

Their chief use is to treat minor pain, i.e. headaches etc, and to control the pain and stiffness in rheumatic disorders and osteoarthritis.

Like we have mentioned, NSAIDS have three major therapeutic actions:

  • Analgesic – pain relief,
  • Antipyretic – temperature reduction and,
  • Anti-inflammatory – reduce tissue inflammation.

What is the Mechanism of action of NSAIDS?

Two enzymes are concerned with the formation of prostaglandins: cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The prostaglandins produced by COX-2 are responsible for pain and inflammation.

NSAIDs block prostaglandin production. COX-1 has a protective effect on the stomach lining.

Most NSAIDs block both COX-1 and COX-2. Although they relieve pain and inflammation, they may cause peptic ulcers. Due to this effect, selective COX2 inhibitors have been developed and are less likely to cause stomach ulceration.

THE SALICYLATES

Aspirin (Acetyl salicylic acid)

This drug has been in used since the year 1899.

Administration and absorption - Asprin is Usually given by mouth and is rapidly given by mouth and is rapidly absorbed from both the stomach and ileum.

Activation and distribution

Once in circulation and tissues, aspirin is converted into the active metabolite salicylate, in the liver; Aspirin is therefore a prodrug.

In higher therapeutic doses, some of the salicylate becomes bound to plasma proteins.

Mechanism of action

Inhibition of prostaglandins. Aspirin is a non-selective inhibitor (it inhibits both COX-1 & COX- 2). It is effective against pain of low intensity and particularly that of rheumatoid arthritis.
Asprin is a weaker analgesic than the morphine type drugs. It produces no sedation, tolerance or physical dependence.

Aspirin is also an antipyretic - It rapidly reduces fever by promoting heat loss (sweating, cutaneous vasodilation). The control of body temperature is regulated by a center in the hypothalamus, which balances heat production, resulting from metabolism against heat loss.

When a patient develops fever the heat regulating mechanism is set at a higher level than normal. Aspirin acts in this centre by inhibiting prostaglandins production in the hypothalamus and reset temperature control to normal levels in the hypothalamus for as long as aspirin therapy is maintained.

Heat loss is achieved by sweating and by dilatation of blood vessels of the skin. Aspirin is used until the body eliminates the cause of pyrexia.

Signs of inflammation (pain, tenderness, swelling, and vasodilation) are suppressed too by asprin.

Therapeutic uses of aspirin

  • Analgesic
  • Antiinflammatory - arthritis
  • Cardiovascular uses – used to inhibit platelet aggregation.

Adverse drug reaction

  1. Side effects – nausea, vomiting, epigastric pain
  2. Hypersensitivity / idiosyncrasy – though infrequent, they can be serious. Reactions include rashes, rhinorrhoea, asthma.
  3. Antinflammatory doses (3-5 g/day) - produces a syndrome called salicylism – dizziness, tinnitus, vertigo, reversible impairment of hearing and vision, mental imbalance and electrolyte imbalance.
  4. Reye’s syndrome – a rare form of hepatic encephalopathy seen in children having viral (varicella, influenza) infection.
  5. Acute salicylate poisoning – more common in children. Fatal dose in adults estimated to be 15 -30 g, but is considerably lower in children.

Signs include:

Vomiting, dehydration, electrolyte imbalance, acidotic breath, haemorrhage, convulsions and death due to respiratory failure and cardiovascular collapse.

Treatment of asprin overdose.

  • The treatment is symptomatic & supportive
  • Most important cooling and iv fluid with Na+, K+, HCO3- and glucose according to need determined by repeated monitoring.
  • Gastric lavage to remove unabsorbed drug.
  • Forced alkaline diuresis.
  • Blood transfusion and vit K should be given if bleeding occurs.

Precautions and contraindications

  • Patients sensitive to aspirin, in peptic ulcer,
  • Bleeding tendencies & patients receiving anticoagulant drugs.
  • Children suffering from chicken pox or influenza.
  • Chronic liver disease
  • Given during pregnancy it may be responsible for low birth weight.

Drug interactions

Increases the effects of : anticoagulants, oral hypoglycaemics by displacing them from protein binding sites.

PARACETAMOL (ACETAMINOPHEN)

Paracetamol is widely used as a minor antipyretic and analgesic. It has some COX inhibiting properties, although, this action is very weak.

It has no anti-inflammatory actions; therefore, it can not be used in the treatment of rheumatoid arthritis.

The main advantage of paracetamol is that it does not cause indigestion, gastric bleeding, hypersensitivity reactions are rare, it does not affect platelet function or clotting factors.

Therapeutic uses

  • The drug is given orally in tablet form. It is well absorbed and the peak plasma concentrations are usually achieved within 60 minutes.
  • Used as a mild analgesic and antipyretic for children under 12 years old as it does not cause Reye’s syndrome.

Adverse drug reactions are uncommon in normal doses.

Acute paracetamol poisoning

Paracetamol overdose causes dangerous liver damage. The margin of safety is relatively low, and doses as low as 2-3 times the maximum therapeutic doses can be harmful to the liver. If large dose > 10 g in an adult; serious toxicity can occur.

Early Treatment

  • If the patient is brought early; induce vomiting or gastric lavage.
  • Activated charcoal administered orally to prevent further absorption.
  • Other supportive measures as needed.
  • Specific antidote: N acetyl cysteine – it replenishes glutathione stores of the liver and prevents binding of the toxic metabolite.

ANALGESIC MIXTURES WITH ASPIRIN OR PARACETAMOL

There are many mixtures in which aspirin or paracetamol is combined with a small dose of weak opiate, thus the risk of dependence is reduced. These combinations are a little stronger than aspirin or paracetamol and are used for more sever pain. They are very common and are available over the counter.

Among those in common uses are:

  • codeine phosphate + paracetamol
  • Codeine phosphate + aspirin

NSAIDS and the uterus

Prostaglandins can cause contraction of the uterus and are important in the initiation of labour. NSAIDS by preventing prostaglandins formation are useful in reducing period pains and have also been used to prevent premature labour.

Older NSAIDS

  1. Indomethacin (indocid)
  2. Phenylbutazone

Both are associated with problematic side effects. Indomethacin has been used in various forms of arthritis and in acute gout.

It is effective but minor adverse effects, particularly the gastrointestinal tract are common.

Phenylbutazone has serious adverse effects, including agranulocytosis, gastric bleeding, salt and water retention.

NON SELECTIVE COX NSAIDS

  1. Diclofenac
  2. Aceclofenac
  • Ibuprofen
  1. Fenbrufen
  2. Ketoprofen
  3. Meloxicam
  • Naproxen
  • Piroxicam
  1. Sulindac

There are now a large number of NSAIDS available for use in rheumatoid arthritis and allied disorders. These drugs are given to reduce pain in dentistry and that arising from soft tissue and bony injuries.

There are certain general principles that can be applied to this group;

  • There is no preferred drug. Patients vary in their preference, and if one drug is ineffective after 2 weeks of treatment, another drug should be substituted.
  • If satisfactory response is obtained; use the lowest dose.
  • All these drugs may cause gastric irritation.
  • Ibuprofen in doses normally recommended is rather less likely to produce side effects than the others in this group.
  • Several of these drugs are available as suppositories (e.g. Diclofenac, indomethacin, ketoprofen) or as injection (Diclofenac).
  • Some NSAIDS are available over the counter (without a prescription)