Drug Pharmacology: Antihistamine Side Effects, Opioid Classification, and Half-Lives

Antihistamine Side Effects and Pharmacokinetics

Adverse Effects

• Gastrointestinal: Nausea, vomiting, diarrhea, constipation, epigastric pain (in some cases), increased appetite. Examples: Astemizole and Azelastine.
• Central Nervous System (CNS): Sedation. Examples: Azelastine, Cetirizine, and...
• Cardiovascular: QT prolongation by blocking K+ channels. (Observed with) Terfenadine and Astemizole.
• Other Reactions: Headache, rash, hypersensitivity, and anaphylaxis.

Pharmacokinetics (Half-Lives - VM)

Astemizole

VM: 20–24 hours

Cetirizine

VM: 7–10 hours

Elastin

VM: 10–16 hours

Loratadine

VM: 12–15 hours

Mizolastine

VM: 8–13 hours

Etc.

Other antihistamines vary.

Muscle Relaxants (Miorelajantes)

Long-Term Benzodiazepines (Half-Lives)

Diazepam

VM: 20–80 hours

Clonazepam

VM: 18–28 hours

Midazolam

VM: 1–3 hours

Skeletal Muscle Relaxants (Half-Lives)

Carisoprodol

VM: 8 hours

Chlorzoxazone

VM: 1–2 hours

Methocarbamol

VM: 14 hours

Cyclobenzaprine

VM: 2–3 hours

Narcotic Analgesics (Opioids)

Opioid Receptor Effects

Opioids exert effects based on receptor type and location:

• Mu (μ Receptor Effects 1): Analgesia, sedation, nausea and vomiting, constipation, urinary retention, miosis, bradycardia, increased temperature (Tº), and tolerance.
• Mu (μ Receptor Effects 2): Sedation, respiratory depression, dependence.
• Kappa (κ Receptor Effects): Weak analgesia, sedation, respiratory depression, weakness, miosis, low tolerance, no cross-tolerance to Mu (μ).
• Delta (δ Receptor Effects): Respiratory depression, weak analgesia, nausea and vomiting, pruritus, tolerance and cross-tolerance... The classified into δ receptors.

Classification of Opioids

1. Pure Agonists: Effects determined by the type and location of the stimulated receptor. Examples: Morphine, Codeine, Fentanyl, Tramadol, Dihydromorphone, Methadone, Meperidine, Dihydroxymorphone, Levorphanol, Propoxyphene, Alphaprodine.
2. Partial Agonists: Exhibit a lower intrinsic activity at μ receptors, resulting in clinical effects of lesser magnitude. Example: Buprenorphine.
3. Agonist-Antagonists: Mixed action with agonist activity in one type of receptor and antagonist activity in another. Examples: Pentazocine, Nalbuphine, Butorphanol, Nalorphine.
4. Pure Antagonists: Displace the agonists, leading to reversal of the clinical effect in a dose-dependent manner. Example: Naloxone.

Mechanism of Action (Three Levels)

Opioids act at three primary levels:

1. Posterior horns of the Spinal Cord.
2. Central midbrain and diencephalon.
3. Limbic Cortical Level.

Opioid Pharmacokinetics (Half-Lives)

Codeine (Minor Opioid)

VM: 2–4 hours

Tramadol (Minor Opioid)

VM: Varies

Major Opioids: Morphine, Fentanyl, Meperidine, Methadone.

Opioid with Mixed Action: Buprenorphine.

Antitussives (Cough Suppressants)

Antitussive agents act via different mechanisms:

• Acting on the Cough Center:
  • Opiates: Codeine, Dextromethorphan, Noscapine.
  • Non-Opiates: Clofedianol.
• Acting on the Afferent Limb of the Cough Reflex:
  • Local Anesthetics: Lidocaine, Benzocaine.
• Acting on the Efferent Limb of the Cough Reflex (Mucociliary or Changing Factors):
  • H1 Antihistamines: Diphenhydramine.
  • Anticholinergics: Ipratropium.