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Chapter 1 Part 1: Principles of Pharmacology, most drug absorption occurs…

- - - - CNS stimulants
      - CNS depressants
      - Analgesics (pain relieving)
      - hallucinogens
      - pyschotherapeutics
- - - - therapeutic effects: drug-receptor interaction produces DESIRED CHANGES (physical or behavioral)
      - all other effects are SIDE EFFECTS
      - want to MINIMIZE side effects and MAXIMIZE therapeutic effects
    - - Specific effects: actually based on PHYSICAL AND BIOCHEMICAL interactions of a drug with a TARGET SITE in living tissue
      - Nonspecific effects: NOT based on drug-receptor interaction
        
        ex. Placebo effect: belief in a drug may produce REAL PHYSIOLOGICAL EFFECTS despite LACK of chemical activity (may work bc of CLASSICAL CONDITIONING)
        
        how to evaluate specific vs. non-specific effects? DOUBLE-BLIND PLACEBO CONTROLLED STUDY: neither participant nor experimenter knows what group participant is in (placebo or not), random placement
- - - - Route of administration: how and where a drug is administered influences HOW MUCH drug reaches its target site and HOW QUICKLY the effect occurs
        
        Enteral (GI tract) vs. Parenteral
        
        enteral: ORAL (pill)
        
        enteral methods are SLOW and produce VARIABLE BLOOD LEVELS of the drug
        
        parenteral: injection, inhalation, topical, snorting
      - Absorption and distribution: movement of the drug from SITE OF ADMINISTRATION --> BLOOD CIRCULATION
        
        unless given IV, drug must cross SEMI-IMPERMEABLE membranes before it reaches systemic circulation
        
        Oral (PO): drug must pass through WALL OF STOMACH OR INTESTINE into bloodstream (must be resistant to destruction by stomach acid/enzymes)
        
        highly variable blood levels
        
        first pass metabolism (pre-systemic metabolism): defense mechanism
        
        potentially harmful chemicals pass via the PORTAL VEIN (from GI tract) to the LIVER --> chemically altered
        
        CYP450 enzymes in liver
        
        reduces bioavailability of the drug
        
        other contributors: enzymes in GI lumen, gut wall, and bacterial enzymes
        
        the reason why drug blood levels are irregular, unpredictable, and rise slowly than other methods of administration
        
        rate of gastric emptying: food SLOWS movement of drugs into the intestine
        
        ex. drinking alcohol on empty stomach --> more drunk quicker
        
        most drugs aren't fully absorbed until they reach the SMALL INTESTINE
        
        Inhalation: drug passes DIRECTLY from LUNGS --> BLOOD --> HEART --> BRAIN (via carotid)
        
        rapid absorption because of the many PULMONARY CAPILLARIES
        
        rapid effect on the brain (within seconds)
        
        Intranasal: direct nose --> brain transport via olfactory nerve pathways
        
        Local and Systemic effects
        
        Local: nasal passages
        
        Systemic: moves across a SINGLE epithelial layer into brain (AVOIDS first-pass metabolism)
        
        BYPASS the Blood-Brain-Barrier (olfactory transfer)
        
        achieves DIRECT ACCESS to CSF
        
        Intravenous (IV): drug passes into HEART, then LUNGS, back to HEART to the BRAIN
        
        most RAPID AND ACCURATE
        
        Gene therapy: application of DNA (which encodes a specific protein) to a particular target site
        
        CAR-T cell therapy: cell-based therapy for cancer attack and kill cancer cells
        
        DNA can be used to INCREASE or BLOCK expression of gene product to correct clinical condition
- - - - lipid solubility INCREASES absorption of drug into the blood, determines how readily a drug will pass lipid barriers to enter brain
        
        most drugs ARE NOT LIPID-SOLUBLE (weak acids or bases that ionize when dissolved in water)
        
        ionization depends on pH and pKa
        
        drugs are absorbed in body fluids that differ in pH
        
        WEAK ACIDS ionize MORE READILY in a BASIC environment and are LESS IONIZED in an ACIDIC environment
        
        WEAK BASES ionize MORE READILY in an ACIDIC environment and are LESS IONIZED in a BASIC environment
        
        environments
        
        stomach fluid: HIGHLY ACIDIC
        
        small intestine: WEAKLY ACIDIC
        
        blood: WEAKLY BASIC
        
        drugs that are HIGHLY IONIZED are POORLY ABSORBED from GI, CANNOT be given by PO
        
        less ionized = more lipid soluble
        
        ex. Aspirin (weak acid)
        
        in the stomach (highly acidic), aspirin is mostly NON-IONIZED (in-tact)
        
        lack of charge makes it more LIPID SOLUBLE
        
        absorbed READILY from stomach --> blood
        
        2 more items...
- - - - Highest concentration of a drug occurs where blood flow is GREATEST
        
        lipid soluble drugs are readily distributed to brain tissue and can EASILY ENTER BRAIN TISSUE
        
        Blood Brain Barrier: separation between BRAIN CAPILLARIES and the BRAIN/CSP
        
        semi-permeable: allows lipid-soluble molecule but NOT IONS
        
        functions
        
        protect brain from foreign substances (i.e. viruses, bacteria)
        
        shield brain from hormones and neurotransmitters from the rest of the body
        
        maintain homeostasis
        
        some brain areas are not isolated (circumventricular organs - CVOs)
        
        AREA POSTREMA or chemical trigger zone (CTZ) in the medulla
        
        MEDIAN EMINENCE of the hypothalamus
  - - - Neonatal abstinence syndrome: babies addicted to opioids
- - - - affects MAGNITUDE AND DURATION of drug action
        
        DELAYS effects
        
        basis for drug testing
        
        individual variability
        
        REDUCES concentration of drug at its sites of action
      - nonselective
        
        drugs remain in the body for extend periods
        
        similar drugs can COMPETE for the same depot binding sites --> overdose