CNS and Analgesics Quiz

Central Nervous System (CNS)

• The CNS consists of the brain and spinal cord
• It integrates information received from, and coordinates and influences the activity of, all parts of the bodies of bilaterally symmetric animals

Drugs Acting on CNS

• Analgesics
  • Relieve pain
  • Two main groups:
    • Opioid (Narcotic) Analgesics:
      • Most powerful
      • Relieve pain except itching
      • Can produce addiction
      • Examples: Morphine and codeine
    • Non-opioid Analgesics (analgesics- antipyretics):
      • Mild analgesics
      • Effective for certain types of pain (e.g., headache, toothache)
      • Not addictive
      • Example: NSAIDs (e.g., salicylates, paracetamol)
• Narcotic Analgesics
  • Derived from opium alkaloids
  • Few are used clinically
  • Example: Morphine (8-15mg by injection)

Pharmacological Actions of Morphine (CNS)

• Centers Depressed by Morphine
  • Cortical pain center
  • Respiratory center
  • Cough center
  • Inhibition of the polysynaptic spinal reflexes
  • Inhibition of the vasomotor center (in large doses)
• Centers Stimulated by Morphine
  • Vomiting center (CTZ in medulla) leading to nausea and vomiting
  • Occulomotor center
  • Stimulation of monosynaptic spinal reflexes (stretch reflex)
  • Release of antidiuretic hormone (ADH) from the posterior pituitary
  • Stimulation of cardiovagal center leading to slow and full pulse
• Opioid Receptors
  • Several types (mu (μ), kappa (к), delta (δ))
  • Found in the nervous system and other tissues
  • Mu (μ) receptors: Supraspinal analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation, miosis
  • Kappa (к) receptors: Spinal analgesia, miosis, sedation
  • Delta (δ) receptors: Supraspinal analgesia

Tolerance

• Failure of responsiveness to a usual dose of the drug
• Develops to the analgesic and respiratory depressant actions of Morphine after 10-14 days

Therapeutic Uses of Morphine

• Powerful analgesic for severe pain
• Pre-anesthetic medication (10-15mg subcutaneously or IM one hour before general anesthesia)
• Alleviating dyspnea
• Certain cases of severe cough (e.g., cancer of the bronchial tree)
• Certain cases of severe diarrhea (after removing the poison causing the diarrhea)

Codeine (Methyl Morphine)

• Less potent
• Produces constipation
• Nausea and vomiting are less
• Less addiction
• Uses: cough suppressant, analgesic with aspirin and paracetamol

Synthetic Morphine Derivatives

• Heroin (Diacetylmorphine)
• Pethidine
• Fentanyl
• Methadone
• Loperamide (Imodium) and diphenoxylate

Opioid Antagonists

• Nalorphine (partial agonist at mu receptors, partial antagonist at delta and kappa receptors)
• Naloxone (pure antagonist at all opioid receptors)
• Naltrexone (longer duration of action than naloxone)
• Therapeutic Uses: Treatment of acute morphine poisoning. Diagnosis of opium addiction.

Sedative-Hypnotic Drugs

• Benzodiazepines (BZs): most widely used anxiolytic drugs
  • Mechanism of Action: Potentiate GABA-ergic inhibition, increasing GABA receptor affinity for GABA, leading to enhanced hyperpolarization and neuronal inhibition
  • Pharmacological Actions: Reduction of anxiety, sedation, induction of sleep, muscle relaxation, anticonvulsant effects
  • Classification: Short-acting (triazolam), Intermediate-acting (alprazolam), Long-acting (diazepam)
• Zolpidem
  • Mechanism of action: Binds selectively to a subset of BZs receptors, facilitating GABA-mediated neuronal inhibition
• Barbiturates
  • Non-selective CNS depressants, ranging from sedation to hypnosis and unconsciousness
  • Mechanism of action: Facilitate GABA action at multiple sites, activating GABA receptors and prolonging chloride channel opening, increasing neuronal membrane hyperpolarization

CNS Stimulants

• Stimulation of CNS can be produced in humans by substances with few clinical uses, but some are drugs of abuse
• Categories: Convulsants and respiratory stimulants, Psychomotor stimulants, Psychotomimetic drugs (hallucinogens)
• Examples of analeptics: Nikethamide, Doxapram

Methylxanthines

• Include theophylline (tea), theobromine (cocoa), and caffeine (highest concentration in coffee, tea, cola drinks, chocolate, candy)
• Mechanism of action: Translocation of extracellular calcium, inhibition of phosphodiesterase leading to increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)
• Therapeutic Uses: Combination with salicylates to relieve simple headache, with ergotamine to relieve migraine, stimulate depressed CNS in alcohol ingestion, bronchial asthma, biliary colics, congestive heart failure, cardiac edema

Anti-Epileptic Drugs

• Carbamazepine: Use-dependent blockade of Na+ channels, suppressing repetitive neuronal firing, reduces propagation of abnormal impulses, attenuates action and release of glutamate
• Phenytoin (diphenylhydantoin): Use-dependent blockade of Na+ channels, blockade of L-type Ca2+ channels, potentiation of GABA action at GABAA receptors
• Lamotrigine: Use-dependent inhibition of neuronal Na+ channels, interferes with synthesis of glutamate and aspartate, reduces glutamate release (possibly through inhibition of voltage-sensitive Ca2+ channels)
• Sodium valproate: Use-dependent blockade of Na+ channels, potentiation of GABA by enhanced synthesis and release (with reduced degradation), attenuation of the excitatory action of glutamate

General Anesthetics

• General anaesthesia: state of loss of sensation, controllable reversible loss of consciousness, skeletal muscle relaxation
• Stages: I (analgesia), II (excitement), III (surgical anesthesia), IV (medullary paralysis)
• Classification: Inhaled volatile agents (hydrocarbons), IV anesthetic drugs

Local Anesthetics

• Definition: Agent that interrupts pain impulses in a specific region without loss of consciousness
• Mechanism of action: Block nerve conduction by interacting directly with receptors on neuronal Na+ channels, inhibiting Na+ ion influx; impairing propagation of action potential
• Factors affecting onset, intensity, and duration: Lipid solubility (lipophilic more potent), Protein binding (higher binding = longer action), pKa (pH at which 50% is ionized; closer pH and pKa = faster onset)