Pharmacology: Autacoids and Antihistaminics

Autacoids

Definition and Classification

• Autacoids: local hormones with heterogenous structures and diverse pharmacological actions
• Classified into:
  • Amines: histamine, serotonin
  • Ergot alkaloids
  • Vasoactive peptides: angiotensin II, vasopressin, endothelin, natriuretic peptides, substance P, neurotensin
  • Fatty acid derivatives: eicosanoids, platelet-activating factor (PAF)

Histamine

Chemistry and Functions

• Amine formed from amino acid histidine
• Functions:
  • Inflammation
  • Immediate allergic reaction
  • Neurotransmitter
  • Neuromodulator

Release of Histamine

• Release mechanisms:
  • Immunologic reaction (allergy)
  • Mechanical injury
  • Inflammation
  • Chemical stimulation (drugs, toxins)

Histamine Receptors

• Four types of receptors:
  • H1: endothelium, smooth muscles, brain, skin
  • H2: gastric mucosa, cardiac muscle, brain
  • H3: presynaptic neurons
  • H4: leukocytes, bone marrow

Actions of Histamine

• Vasoactive effects:
  • H1: vasodilation, hypotension, increased capillary permeability
  • H2: positive chronotropic and inotropic effects
  • H3: decreased transmitter release
  • H4: chemotactic effect

Antihistamines

• Types:
  • Physiologic antagonists (adrenaline)
  • Histamine release inhibitors (mast cell stabilizers)
  • Adrenal steroids (inhibit antigen-antibody reaction)
  • Pharmacologic competitive antagonists (H1, H2, H3, H4 receptors)

Antihistaminics (H1 Receptor Blockers)

First Generation

• Examples: diphenhydramine, chlorpheniramine, promethazine
• Characteristics:
  • Lipid soluble
  • Metabolized by liver microsomal enzymes
  • Renal excretion
  • Short duration (4-6 hours)
  • Sedation

Second Generation

• Examples: fexofenadine, loratidine, cetirizine
• Characteristics:
  • Less lipid soluble
  • Metabolized by hepatic microsomal enzymes (CYP3A4)
  • Longer duration (12-24 hours)
  • No sedation

Pharmacodynamics

• Reversible competitive blockade of H1 receptors
• Effects:
  • Relief of allergic symptoms
  • Sedation
  • Antiemetic and antinausea
  • Antiparkinsonian

Therapeutic Uses

• Allergic reactions
• Nausea and vomiting of pregnancy
• Motion sickness prophylaxis
• Sedative-hypnotic

Adverse Effects

• Sedation
• Dizziness
• CNS depression
• Excitation
• Dry mouth
• Constipation
• Urine retention
• Teratogenic

Serotonin (5-HT)

Chemistry and Functions

• Formed from amino acid L-tryptophan
• Functions:
  • Neurotransmitter
  • Neuromodulator
  • Potent stimulant for pain and itching
  • Gastrointestinal tract contraction

Receptors

• Five types of receptors:
  • 5-HT1A and 5-HT1B: CNS
  • 5-HT2: CNS, platelets, peripheral blood vessels
  • 5-HT3: CNS, peripheral nerves
  • 5-HT4: GIT (enteric nervous system)

Agonists and Antagonists

• Agonists:
  • Buspirone (5-HT1A)
  • Triptans (5-HT1D)
  • Itopride (5-HT4)
• Antagonists:
  • Cyproheptadine (5-HT2, H1, muscarinic)
  • Methysergide (5-HT2)

Adverse Effects and Contraindications

• Agonists:
  • Tingling, dizziness, neck pain, chest pain
  • Contraindicated in angina, hypertension, peripheral vascular disease, pregnancy
• Antagonists:
  • Drowsiness, dry mouth, retroperitoneal and pleural fibrosis

Ergot Alkaloids

Chemistry and Classification

• Derivatives of lysergic acid
• Classification:
  • Natural alkaloids
  • Semisynthetic derivatives

Pharmacokinetics

• Poor oral absorption
• Caffeine increases absorption
• Delayed onset and prolonged duration

Pharmacodynamics

• Partial agonist at alpha-1 adrenoceptor and 5-HT2 receptors
• Stimulates oxytocic effect, cardiac inhibitory center, and chemoreceptor trigger zone

Uses

• Acute attack of migraine
• Postpartum hemorrhage
• Subinvolution of uterus
• Variant (Prinzmetal) angina

Adverse Effects and Contraindications

• Cold extremities, tingling, numbness, gangrene, hypertension, nausea, and vomiting
• Contraindicated in coronary heart disease, peripheral vascular disease, hypertension, pregnancy, liver disease, and renal disease

Migraine Headache

Definition and Clinical Picture

• Paroxysmal unilateral headache
• Preceded by aura
• Characterized by unilateral throbbing headache, nausea, and pallor

Prophylaxis

• Avoidance of precipitating factors
• Serotonin antagonists
• Propranolol
• Amitriptyline
• Flunarizine

Treatment

• Mild attack: analgesics, antiemetics
• Severe attack: ergotamine or dihydroergotamine with caffeine, sumatriptan

This quiz covers autacoids, antihistaminics, and serotonin agonists and antagonists, including their therapeutic uses and adverse effects.