Farmol

• Pharmacokinetics


  What our body does to a drug
• Pharmacodynamics


  What the drug does to the body
• Pharmacokinetics process


  1. Adsorption

  2. Distribution

  3. Metabolism

  4. Excretion
• Mechanism of drugs


  • Non-specific
  • Specific - facilitated by the drugs physiochemical properties, Interactions with Macromolecules in body, Osmotic - high to low pressure, Works selectively, Change in pH, Non-specific destruction - disrupts membrane integrity
• Therapeutic Index


  Ratio of the lethal dose to the effective dose
• LD50


  Lethal dose that causes 50% death (animal)
• ED50


  Effective dose that causes 50% of the maximum effect (animal)
• TD50


  Toxic dose that causes 50% toxicity (human)
• TI


  Therapeutic Index = LD50/ED50
• Drug-receptor interaction


  Agonist, Antagonist, Allosteric
• Autocoids


  Chemical substances produced to help heal local injuries
• Classification of autocoid release

  • Immunologic release - Mast cells sensitized by IgE
  • Non-immunologic release - Chemical & physical injury of mast cells
• Types of autocoids


  • Amine derived - Histamine, Serotonin
  • Lipid derived - Prostaglandins, Leukotrienes
  • Peptide derived/vasoactive polypeptide - Angiotensin, Vasopressin
  • Endothelium derived - Nitric Oxide
• Functions of autocoids


  • Inflammation, Allergic reactions, Neurotransmission, Gastric acid Secretion
• Histamine


  Plays a role in allergic, inflammatory reactions & Gastric acid secretion. Therapeutic application: antihistamine
• Locations of histamine


  • All tissues, mostly in the lung, skin, GI tract
  • High conc on mast cells or basophils
  • Mast cells histamine is stored in granules as an inactive complex composed of histamine, Heparin, with avionic protein
• Histamine receptors


  • H1 receptors - coupled to phospholipase C, Smooth muscles
  • H2 Receptors - Stimulate adenyl cyclase enzyme & increase cAMP, Heart, Stomach acid Secretion
  • H3 receptors - G-protein-coupled, Presynaptic sites CNS & Inhibit release of other Neurotransmitters
• Mast cells


  Found in connective tissue throughout the body, especially near blood vessels, nerves, and lymphatic vessels. Activated by IgE-mediated immunologic release and non-immunologic stimuli. Contain granules filled with histamine, heparin, and other mediators. Play a key role in allergic reactions, anaphylaxis, and inflammation.
• Basophils


  Found in the bloodstream and make up about 0.5-1% of all white blood cells. Similar to mast cells in that they contain granules filled with histamine and heparin, but have a different morphology and function. Activated by IgE-mediated immunologic release, but not by chemical or physical injury. Play a role in allergic reactions and inflammation, but to a lesser extent than mast cells.
• Histamine


  A mediator released by mast cells and basophils during activation. Causes vasodilation, increased vascular permeability, smooth muscle contraction, pain and itch, and immune response regulation. Plays a crucial role in the inflammatory response and helps to recruit and activate other immune cells to the site of infection or injury.
• Histamine


  A biogenic amine involved in the immune response and inflammation. Has several functions, including vasodilation, increased vascular permeability, smooth muscle contraction, pain and itch, and immune response regulation. Mediates its effects through four different G protein-coupled receptors (H1, H2, H3, and H4).
• H1 receptor


  A G protein-coupled receptor that mediates the effects of histamine in the body. Activation of the H1 receptor leads to vasodilation, increased vascular permeability, smooth muscle contraction, and pain and itch sensations. Involved in allergic reactions and inflammation.
• H2 receptor


  A G protein-coupled receptor that mediates the effects of histamine in the body. Activation of the H2 receptor leads to increased gastric acid secretion and relaxation of smooth muscle. Involved in gastric function and cardiovascular regulation.
• H3 receptor


  A G protein-coupled receptor that mediates the effects of histamine in the brain and nervous system. Activation of the H3 receptor leads to inhibition of neurotransmitter release and modulation of neuronal activity. Involved in neurotransmission and regulation of wakefulness and appetite.
• H4 receptor


  A G protein-coupled receptor that mediates the effects of histamine in the immune system. Activation of the H4 receptor leads to chemotaxis and activation of immune cells. Involved in immune response regulation and inflammation.
• Autocoid


  A hormone that is produced and acts within the same cell
• Drugs related to PAF


  Drugs that affect the activity of PAF (Platelet-activating factor)
• NOU-Selective N-SAIDs


  • Inhibit COx-1
  • Can cause contraction of pregnant uterus
  • Can cause peptic ulcer bleeding
  • Inhibition of gastric acid secretion
  • Bronchial increase of gastric mucus secretion
  • Asthma
  • Contraction of smooth muscles
  • Nephrotoxicity
• PGF2as


  • ↑ Non-selective: Cox1/COX-2 inhibitors
  • Contraction of bronchi
  • Contraction of myometrium
  • NSAIDs & COX-2 inhibitors: selective (coxibs)
  • Preferential selective Cox-3 inhibitors
  • Antipyretic Analgesics: Ibuprofen, aspirin, naproxen, metehamic acid
  • For: PGF2a (dinoprost)
  • For: PGEC (dinoprostone) - Termination of pregnancy
• Types of COX


  • Cox-1 (constitutive) - acts in physiological conditions
  • COX-2 (inducible) - induced in inflammatory cells by pathological stimulus
  • Cox-3 - in brain
• Autocoid


  A hormone that is produced and acts within the same cell
• Drugs related to PAF


  NOU-Selective N-SAIDs, PGE1 & 2, PGF2α, PGE, Cox-1, Cox-2, Cox-3
• NOU-Selective N-SAIDs


  • Inhibit COx-1
• PGE1 & 2


  • Can cause contraction of pregnant uterus, peptic ulcer bleeding, inhibition of gastric acid secretion, increase of gastric mucus secretion, asthma, contraction of smooth muscles, nephrotoxicity
• PGF2α


  • ↑ Non-selective: Cox1/COX-2 inhibitors, contraction of bronchi, contraction of myometrium
• NSAIDs & COX-2 inhibitors

  • Selective (coxibs), preferential selective Cox-3 inhibitors, antipyretic analgesics
• PGE


  Induction of labour, termination of pregnancy
• PGF2α


  Prostaglandin F2α
• Cyclooxygenase (COX)


  Exist as 3: Cox-1 (constitutive), Cox-2 (inducible), Cox-3 (in brain)
• Cox-1


  Acts in physiological conditions