Please enable JavaScript.

Coggle requires JavaScript to display documents.

Absorption, Distribution, Metabolism, Elimination (Absorption (journey…

- - - - Passive movement (no energy expended)
        
        Majority rely on Diffusion
        
        Simple Diffusion
        
        Lipid solubility
        
        determines how well/how much of a drug passes through a membrane
        
        Partition co-efficient- the ratio of drug dissolving in oil/water
        
        1 more item...
        
        Facilitated Diffusion
        
        Solute Carries (SLC)
        
        facilitates transport of a single species down its electrochemical gradient
        
        Organic Anion Transporters (OAT)
        
        Organic Cation Transporters (OCT)
        
        2 more items...
        
        Aqueous pores
        
        formed by aquaporin proteins
        
        ~0.4nm diameter
        
        only small water soluble molecules
        
        too small to admit most drugs
      - Active Transport
        
        ATP-binging cassette (ABC) transporters
        
        Specialized transporter complexes
        
        mediate cell uptake and movement across membranes against concentration gradients
        
        p-glycoprotein transporters
        
        Primary group, superfamily
        
        1 more item...
        
        Both SLC and ABC transporters may be expressed on different surfaces of polar cells
        
        mediating movement of molecules into the cytoplasm and some mediating transport out the cell on either basolateral or luminal surfaces
        
        1 more item...
        
        Pinocytosis
        
        Only important for very large molecule that are unable to defuse through the membrane due to size
        
        Invagination (inward cavitation) of part of the cell membrane forming a vacuole in the cell cytoplasm containing extracellular material
        
        contents released into cell
        
        vacuole passes through the cell to the opposite side to the extracellular space
- - - - almost all drugs reversibly bind plasm proteins
        
        main proteins: albumin, various lipoproteins, glycoproteins, and beta globulins
        
        level of binding depends on affinity of the drug for that plasma protein
        
        binding can range from 1-99%
        
        Equilibrium is maintained as free drug is taken up into the tissues, bound drug is released from the proteins and into free circulation
        
        Plasma protein binding is saturable
        
        2 more items...
    - - assumes there are 2 places the drug can reside
        
        Good estimation of how well drug is able to leave circulation and penetrate into tissues
        
        Plasma
        
        low Vd = drug is primarily still in circulation
        
        Everywhere else
        
        High Vd = drug has left circulation
      - Does not take into account metabolism, so it is most relevant immediately after administration
- - - - Efficient pathways for dealing with foreign substances
        
        Main site for drug metabolism : Liver
        
        metabolic processes broadly prepare drugs for elimination by
        
        1st: making it more water soluble, less able to be re-absorbed by the renal tubule
        
        Phase 1: primarily mediated by cytochrome system associated with the endoplasmic reticulum in cells
        
        adds a reactive residue to the processed molecule
        
        2 more items...
        
        2nd: altering its structure such that it reduces its intrinsic efficacy and so aids in excretion
        
        Phase 2
        
        Conjugation of side chains to drugs
        
        6 more items...
        
        locations
        
        4 more items...
        
        1st pass effect
        
        metabolism of a drug prior to reaching circulation
        
        by gastric mucosa
        
        1 more item...
        
        after absorption from the gut into the hepatic portal vein and so directly to the liver where most metabolism occurs
        
        1 more item...
- - - - Renal Route- Main site for drug excretion: Kidney
        
        Tubular secretion
        
        Carrier mediated transport
        
        Drugs that are protein bound may still be readily excreted via the carrier system
        
        tubular secretion involved specific transport proteins
        
        can be antagonized
        
        1 more item...
        
        Passive diffusion
        
        Glomerular filtration
        
        molecules smaller than mx 5,000-15,000 readily pass and cleared
        
        Plasma protein binding by drugs is highly significant during excretion
        
        plasma proteins (ex- albumin) and most proteins, too large to pass
        
        Plasma protein bound drug is therefore not filtered
        
        1 more item...
      - Hepatic Route
        
        Various substances (ex- drugs) transported from plasma to bile via SLC and P-gp transporters
        
        Drug conjugates may be concentrated in bile and after release may lose the conjugate through hydrolysis
        
        releasing relatively high concentrations of reactivated drug
        
        drug is potentially free to be reabsorbed into the body
        
        Enterohepatic circulation can reabsorb excreted drugs
        
        1 more item...
        
        Feces
      - breast milk
      - sweat
      - tears
      - saliva