History of pharmacology & contributions of various scientists in pharmacology
Pharmacology ?
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Transcript of Pharmacology ?
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Copyright © 2008 Lippincott Williams & Wilkins.
Chapter 7
Introduction to Cell Physiology
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Chemotherapeutic AgentsChemotherapeutic Agents
• Alter cellular function or disrupt cellular integrity, causing cell death
• Prevent cellular reproduction, eventually leading to cell death
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Chemotherapeutic DrugsChemotherapeutic Drugs
• Destroy organisms that invade the body
– Bacteria, viruses, parasites, protozoa, fungi
• Destroy abnormal cells within the body
– Neoplasms and cancers
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Parts of a Human CellParts of a Human Cell
• Nucleus
• Cell membrane
• Cytoplasm
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Structure of a CellStructure of a Cell
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Cell NucleusCell Nucleus
• Contains genetic material
– Necessary for cell reproduction
– Regulates cellular production of proteins
• Each cell is “programmed” by the genes for the production of specific proteins
– Allows the cell to carry out its function
– Maintains cell homeostasis or stability
– Promotes cell division
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Cell MembraneCell Membrane
• Surrounds the cell
• Separates the intracellular fluid from the extracellular fluid
• Essential for cellular integrity
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Structure of a Lipid Cell MembraneStructure of a Lipid Cell Membrane
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Organelles of the CytoplasmOrganelles of the Cytoplasm
• Mitochondria
• Endoplasmic reticulum
• Free ribosomes
• Golgi apparatus
• Lysosomes
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Components of Cell MembraneComponents of Cell Membrane
• Cell membrane is made up of lipids and proteins
• Several lipids make up the cell membrane
– Phospholipids
– Glycolipids
– Cholesterol
• Lipid layer provides a barrier for the cell and maintains homeostasis of the cell
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Receptor SitesReceptor Sites
• Found on the cell membrane
• Specific receptor sites allow interaction with various chemicals
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Identifying MarkersIdentifying Markers
• Surface antigens
• Important in the role of cellular immunity
• Histocompatibility proteins allow for self-identification
• The body’s immune system recognizes these proteins and acts to protect self-cells and to destroy non–self-cells
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ChannelsChannels
• Channels or pores allow for the passage of substances into and out of the cell
• Some drugs are designed to affect certain channels within the cell
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Cell PropertiesCell Properties
• Endocytosis
– Involves incorporation of material into the cell
– Pinocytosis and phagocytosis occur
• Exocytosis
– Allows a cell to move a substance to the cell membrane and secrete the substance outside the cell
– Hormones, neurotransmitters, and enzymes are excreted into the body by this process
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Homeostasis of the CellHomeostasis of the Cell
• Passive transport
– Happens without the expenditure of energy and can occur across any semipermeable membrane
– Occurs by diffusion, osmosis, and facilitated diffusion
• Active transport
– Energy-requiring process
– Movement of particular substances against a concentration gradient
– Important in maintaining cell homeostasis
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Passive TransportPassive Transport
• Diffusion
– Does not require energy
– The movement of solutes from a region of high concentration to a region of lower concentration across a concentration gradient
• Osmosis
– Does not require energy
– Movement of water from an area low in solutes to an area high in solutes
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Phases of the Cell CyclePhases of the Cell Cycle
• G0 phase
– Resting phase
• G1 phase
– Gathering phase • S phase
– Synthesizing phase
• G2 phase
– Last substances needed for division are collected and produced
• M phase – Actual cell division occurs, producing two identical
daughter cells
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Cell CycleCell Cycle
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Cell PhysiologyCell Physiology
• May alter the cell membrane, causing the cell to rupture and die
• May deprive the cell of certain nutrients, altering the proteins that the cell produces and interfering with normal cell functioning and cell division
• May affect the normal cells of patients to some extent
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Chapter 8
Anti-infective Agents
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Drug Therapy Across the LifespanDrug Therapy Across the Lifespan
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Development of Anti-infective TherapyDevelopment of Anti-infective Therapy
• 1920s
– Paul Ehrlich worked on developing a synthetic chemical effective against infection-causing cells only
– Scientists discovered penicillin in a mold sample
• 1935
– The sulfonamides were introduced
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Mechanisms of ActionMechanisms of Action
• Interfere with biosynthesis of the bacterial cell wall
• Prevent the cells of the invading organism from using substances essential to their growth and development
• Interfere with steps involved in protein synthesis
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Mechanisms of Action (cont.)Mechanisms of Action (cont.)
• Interfere with DNA synthesis
• Alter the permeability of the cell membrane to allow essential cellular components to leak out
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Mechanism of Anti-infective AgentsMechanism of Anti-infective Agents
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Anti-infective ActivityAnti-infective Activity
• Anti-infectives vary in their effectiveness against invading organisms
• Some are selective: they are effective only for a small number of organisms
• Bactericidal: kill the cell
• Bacteriostatic: prevent reproduction of the cell
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Narrow Spectrum vs Broad SpectrumNarrow Spectrum vs Broad Spectrum
• Narrow spectrum of activity
– Effective against only a few microorganisms with a very specific metabolic pathway or enzyme
• Broad spectrum of activity
– Useful in treating a wide variety of infections
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Human Immune ResponseHuman Immune Response
• Goal of anti-infective therapy is reduction of the population of the invading organism
• Drugs that eliminate all traces of any invading pathogen might be toxic to the host as well
• Immune response is a complex process involving chemical mediators, leukocytes, lymphocytes, antibodies, and locally released enzymes and chemicals
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Problems With Treating Infections in Immunosuppressed Patients
Problems With Treating Infections in Immunosuppressed Patients
• Anti-infective drugs cannot totally eliminate the pathogen without causing severe toxicity in the host
• These patients do not have the immune response in place to deal with even a few invading organisms
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ResistanceResistance
• Anti-infectives act on a specific enzyme system or biological process; many microorganisms that do not act on a specific system are not affected by the particular drug
• This is considered natural or intrinsic resistance to that drug
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Acquired ResistanceAcquired Resistance
• Microorganisms that were once sensitive to the particular drug have begun to develop acquired resistance
• This results in serious clinical problems
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Ways Resistance Develops Ways Resistance Develops
• Producing an enzyme that deactivates the antimicrobial drug
• Changing cellular permeability to prevent the drug from entering the cell
• Altering transport systems to exclude the drug from active transport into the cell
• Altering binding sites on the membranes or ribosomes, which then no longer accept the drug
• Producing a chemical that acts as an antagonist to the drug
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Preventing ResistancePreventing Resistance
• Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used
• Make sure doses are high enough, and the duration of drug therapy long enough
• Be cautious about the indiscriminate use of anti-infectives
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Identification of the PathogenIdentification of the Pathogen
• Identification of the infecting pathogen is done by culture
• A culture of a tissue sample from the infected area is done
– A swab of infected tissue is allowed to grow on an agar plate
– Staining techniques and microscopic examination identify the bacterium
• Stool can be examined for ova and parasites
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Sensitivity of PathogenSensitivity of Pathogen
• Shows which drugs are capable of controlling the particular microorganism
• Important to be done for microorganisms that have known resistant strains
• Along with a culture, identifies the pathogen and appropriate drug for treatment
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Factors Affecting Prescribing Anti-infective Agents
Factors Affecting Prescribing Anti-infective Agents
• Identification of the correct pathogen
• Selection of the right drug
– One that causes the least complications for that particular patient
– One that is most effective against the pathogen involved
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Combination TherapyCombination Therapy
• Use of a smaller dosage of each drug
• Some drugs are synergistic
• In infections caused by more than one organism, each pathogen may react to a different anti-infective agent
• Sometimes, the combined effects of the different drugs delay the emergence of resistant strains
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Adverse Reactions to Anti-infective TherapyAdverse Reactions to Anti-infective Therapy
• Kidney damage
• Gastrointestinal (GI) tract toxicity
• Neurotoxicity
• Hypersensitivity reactions
• Superinfections
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Prophylaxis of Anti-infective AgentsProphylaxis of Anti-infective Agents
• People traveling to areas where malaria is endemic
• Patients who are undergoing gastrointestinal or genitourinary surgery
• Patients with known cardiac valve disease, valve replacements, and other conditions requiring invasive procedures