Lec 1& 2
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Pharmacology is the study of how drugs interact with living systems. It has two main areas - pharmacokinetics, which examines what the body does to drugs, and pharmacodynamics, which examines what drugs do to the body. There are several factors that influence drug absorption including the route of administration, physicochemical properties of the drug, dosage form, and concentration of the drug. Absorption involves movement of the drug from its site of entry into blood or lymph without chemical change, and can occur via passive diffusion, active transport, or endocytosis.
Lec 1& 2
- 1. Please, shut down your mobile
- 2. Faculty of PharmacyDepartment of PharmacologypharmacologyGeneral Pharmacology3rd year pharmacy studentsBy “Dr. Shimaa Elshazly”
- 3. What is pharmacology?The term pharmacology comes from the Greek words:•Pharmakon- drug or medicine•Logos- the truth about or a rational discussion …………Truth about medicine• Pharmacology is the study of howdrugs exert their effects on livingsystems.• More specifically it is the study ofthe interactions between a livingorganism and drugs that alter normalbiochemical function.
- 4. History of PharmacologyEarly pharmacologyfocused on naturalsubstances, mainly plantextracts.
- 5. Modern approach Pharmacology is a discipline as a bridge, not only to connect pharmacy with medicine, but also to link foundational medicine to clinical medicineFoundational MedicineClinical MedicinePharmacologyMedicinePharmacyManufacture of DrugsResearch of Drugs
- 6. ……..Subdivisions of PharmacologyClinical Pharmacology:application of pharmacodynamics and pharmacokinetics to human.•Toxicology -Study ofharmful effects of drug•Posology- How medicines aredosed or calculation of dose•Pharmacognosy-Development of medicinalsubstances obtained fromplants
- 7. Division of Pharmacology:The science of pharmacology is divided into TWO important and interrelated areas : Pharmacokinetics: Study of the absorption,distribution, metabolism and excretion of drugs(ADME).……………..what the body does to the drugB. Pharmacodynamics: Study of the molecular,biochemical and physiology effects of drugs oncellular systems and their mechanisms of action.……………..what the drug does to the body
- 8. What Is a Drug? A drug is a substance which when given to a patient can affect his body functions. This effect is useful in the treatment of a disease ( therapeutic ).If given in high dose it may cause a disease due to the toxicity of the drug itself. In other meaning:Chemical agents used in the diagnosis, treatment, or prevention of diseaseWhat are the sources of a drug?1- Natural2- Semisynthetic3- Purely synthetic4.Mineral Origin5.Genetic Engineering
- 9. 1- Natural: Plant Origin: eg.Atropine from belladonna & Morphine from Opium. b) Animal Origin: eg. Insulin, calcitonin etc. 2- Semisynthetic: These are compounds that are obtained from natural source and subjected to chemical modification eg.Penicillins and heroin (prepared by acetylation of morphine). 3- Purely synthetic: Are purely chemically synthesized. eg. The majority of drugs. 4.Mineral Origin:eg. Iodine, magnesium sulphate 5.Genetic Engineering:a) Gene Therapy. b) Recombinant DNA as the production of human insulin from bacterial origin.
- 10. Pharmacokinetics of drugs(ADME)……………..what the body does to the drugAre studies of: Absorption
- 12. Metabolism
- 13. Excretion or Eliminationof drugs
- 15. Drug Absorption• Absorption is the movement of a drug from its site of application into the blood or lymphatic system without being chemically altered• Mathematically it is define in terms of Bioavailability (Rateand extent of absorption).
- 16. BioavailabilityDefinition: Rate and extent of absorption i.e. Ka (Absorption constant)………. Rate of absorption. Area under curve (AUC)………. extent of absorption.• for i.v.: 100%• for non i.v.: ranges from 0-100%e.g. lidocaine bioavailability is 35% due to destruction in gastric acid and liver metabolism
- 17. Process of AbsorptionIn order for a drug to be absorbed, it must be able topass through cell membranes (which is a lipidbarrier)• Lipid soluble drugs would be ideal to pass through themembrane easily.• Drugs can be absorbed by 4 main ways :1. Simple diffusion = passive diffusion. 2. Active transport. 3. Facilitated diffusion. 4. Pinocytosis (Endocytosis).
- 18. Cell membrane
- 20. Simple or passive diffusion Water soluble drug (ionized or polar) is readily absorbed via aqueous channels or pores in cell membrane.
- 21. Lipid soluble drug (nonionized or non polar) is readily absorbed via cell membrane itself.
- 23. Occurs along concentration gradient. Non selective
- 24. Not saturable
- 25. Requires no energy
- 26. No carrier is needed
- 27. Depends on lipid solubility.Simple diffusionLow concHigh conc
- 28. Simple diffusionDrugs exist in two forms ionized (water soluble) & nonionized forms (lipid soluble) in equilibrium.Drug ionized + nonionized Only nonionized form is absorbable.
- 29. Six things influence the rateof diffusionConcentration gradientBig concentration difference (Fick’s Law) increasediffusion.
- 30. Size of molecule involved Large molecules slowdiffusion
- 31. Distance the molecule has to travelShort distance increase diffusion
- 33. Solubility of the molecule
- 34. Surface area of the membrane over which the molecule can work.Large surface area increase diffusionActive Transport Relatively unusual.
- 35. Occurs against concentration gradient.
- 36. Requires carrier and energy.
- 37. Specific
- 38. Saturable.
- 39. Iron absorption.
- 40. Uptake of levodopa by brain.
- 41. Carrier-mediated Facilitated DiffusionOccurs along concentration gradient.
- 43. Selective.
- 44. Saturable.
- 45. No energy is required.
- 46. Selection is by size; shape; charge.
- 47. Common molecules entering/leaving cells this way include glucose and amino-acids.
- 52. Phagocytosis (Endocytosis & Exocytosis)Endocytosis: uptake of membrane-bound particles. Exocytosis: expulsion of membrane-bound particles. High molecular weight drugs or Highly lipid insoluble drugs
- 53. Factors which influence the rate of absorption:– Routes of drug administration– The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug
- 54. Routes of drug administrationEnteral via gastrointestinal tract (GIT).Oral SublingualRectal Parenteral administration = injections.Topical applicationInhalation
- 56. First pass MetabolismMetabolism of drug in the gut wall or portalcirculation before reaching systemic circulationSo the amount reaching system circulation is less than the amount absorbedWhere ? Liver
- 57. Gut wall
- 58. Gut LumenResult ? Low bioavailability.
- 59. Short duration of action (t ½).First pass effect
- 60. Dosage forms Capsules Tablets Syrup SuspensionHard- gelatin capsuleSoft- gelatin capsuleTabletsSpansule
- 61. Sublingual
- 63. Parenteral administrationIntradermal (I.D.) (into skin)Subcutaneous (S.C.)Intramuscular (I.M.)Intravenous (I.V.) (into veins)Intra-arterial (I.A.) (into arteries)Intrathecal (I.T.) (cerebrospinal fluids )Intraperitoneal (I.P.) (peritoneal cavity)Intra - articular (Synovial fluids)Intracardial
- 66. Ampoule Vial
- 67. 1- Intravenous ( IV ) The drug is injected right into the venous blood.Advantages: Immediate effect.
- 68. Suitable for drugs not absorbed by the gut.
- 69. Rapidly destroyed drugs, short t½ can be infused continuously to provide a steady state of plasma concentrationDisadvantages: Dangerous if given rapidly.
- 70. Prolonged infusion of irritant drugs lead to venous thrombosis.
- 71. Susceptibility to infection if not using aseptic conditions. 2- Intramuscular Injection is made into a large muscle Advantages: Reliable & produces more rapid absorption than SC.
- 72. Could be used for irritant drugs.
- 73. Could be used for depot preparations eg. Long actingpenicillins.Disadvantages: It is painful.
- 74. Not accepted as self administration.
- 75. Risk of infection & formation of abscess.3- Subcutaneous (SC)Just under the skinAdvantages Can be given by the patient
- 76. Slow to obtain sustained drug effect eg. Insulin but generally complete
- 77. Suitable only for nonirritant drugs.Disadvantages Large volume may be painful.
- 78. Tissue damage from irritant drugs
- 79. Maximum of 2 ml injection
- 80. Heat, Vasoconstrictors such as adrenaline greatly decrease the rate of absorption. Produce local effect to: Skin (percutaneous) e.g. allergy testing, topical local anesthesia
- 81. Mucous membrane of respiratory tract (Inhalation) e.g. asthma
- 82. Eye drops e.g. conjunctivitis
- 83. Ear drops e.g. otitis externa
- 84. Intranasal, e.g. decongestant nasal sprayTopical application
- 85. Inhalation
- 86. Nebulizer Atomizer
- 87. Transdermal delivery system (TDS) TDS is a method by which the drug is releasedand absorbed through the skin for systemicabsorption by a medicated adhesive patchapplied to skin * Slow effect (prolonged drug action) e.g. the nicotine patches Advantages: Lead to more stable drug level in the blood.
- 88. Avoid inactivation by first hepatic bypass eg. Nitroglycerine
- 89. Minimal side effects. Factors which influence the rate of absorption:– Routes of drug administration–The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug
- 90. Factor affecting absorption……Physico-chemical properties of drug Molecular weight· Drugs with a small M.W. are absorbed well· Drugs which are large (often proteins) are absorbed poorly. Chemical and enzymatic stability· The drug should be stable in gastric acid and in gut enzymes.e.g. Penicillin G is highly acid labile, or unstable in acid. Aqueous and lipid solubility· For better absorption a drug must have optimum water and lipid solubility or a optimum partition coefficient. If it is highly lipid soluble it would not dissociate in the circulation i.e. Ion trapping. On the other hand, if it is highly water soluble then it will not cross the biological membrane.
- 91. Factor affecting absorption……pH and lipid solubility:Most drugs are either weak acids or weak bases and can exist in either the ionised (less lipid soluble) or unionised (more lipid soluble) form depending on the pH of the surrounding environment.REMEMBER THAT A DRUG IS ABSORBED BETTER IN THEUNIONISED FORM (Lipophillic drug can cross cell membrane)
- 92. Ion TrappingBody fluids where a pH difference will favor trapping of highlylipophillic drugs: e.g. Breast milk , Aqueous humor (eye) ,Vaginal secretions , Prostatic secretionsAspirin is an acidic drug (pKa=5) and exist in the unionised form in stomach (pH 2.0)
- 93. In this form, it can enter the cells of the stomach lining (pH=7.4) where it is ionized and, in this form, it cannot leave the cell.
- 94. The concentration of ionized aspirin inside the cell continues to rise until it saturates and precipitates as crystals, which lead to gastric bleeding.Factors which influence the rate of absorption:– Routes of drug administration– The physicochemical properties of the drug– Dosage forms– Circulation at the site of absorption– Concentration of the drug
- 95. Drug dosage formsDifferent dosage forms have different rate and extent of absorption.
- 96. A syrup has fast rate of absorption as compare to tablet
- 97. A capsule has fast rate of absorption than tablet
- 98. Controlled-release, timed-release, sustained-release dosage form have a uniform absorption and less side effectsThank you