Drug Absorption + Distribution

Drug Absorption + Distribution

1. 4 Stages of Drugs disposition, (ADME)

   • Absorption,Distribution,Metabolism and Excretion
     • Some drugs don't need metabolism to be excreted
   • Way drugs absorbed, Oral, GI tract, Inject, Inhale and skin
     • Rate of absorption depends on route to administer, blood flow at area and solubility and ability to cross membrane
       • Injections absorbed fast into blood supply
         • Eat or skin=slow as has to be absorbed
       • Crossing of membrane the drug needs to be lipid soluble to be fast and water soluble=slow

2. Bio-availability, amount of drug reaching bloodstream when ingested

   • Injection and Inhaling=100% reaches blood and eating/skin=<100%
   • Time course of drug action follows time course of its conc in blood plasma
   • Drug activity falls due to rate of drug being eliminated or conc of drug being dropped

3. MTC= Min Tolerated Conc (above this =side effects) MEC=Min Effective Conc (threshold for drug to act)

4. Oral, usually taken as is easy, cheap, Convenient and no medical supervision needed

   • Disadvantages of Oral like, inefficient as high dose or low solubility will have poor availability and only some of dose taken in
   • Sublingual uptake of drugs, absorb drug into blood straight from mouth
     • Advantages like rapid absorption, bypass liver so no drug lost to fast pass effect of liver, and avoid stomach acid and enzymes
       • Disadvantage hard to hold pill under tongue and only small doses can be taken this way

5. GI absorption, most drugs absorbed in small intestine,75% taken up in 1-3hours.

   • Absorption affected by, Rate of blood flow in small intestine, formulation (size and solubility), enzymes or acids inactivate drugs, drugs become ionised reduces absorption.
     • Food can dilute or bind to drug. The ionisation is when weak acid or base drug go into water
   • Can give drugs via rectum, advantages are that bypass liver and also useful if patients cant swallow
     • Disadvantage is that absorption can be incomplete and erratic

6. Intramuscular (IM) and Subcutaneous (SC) used because safer than intravenous and faster effects

   • Increase absorption by warming/massaging of area to increase absorption, shock and trauma can reduce absorption
     • IM and SC absorption depends on formulation, i.e. SC implants hormone pellets and slowly release over time, like oestrogen and progesterone as birth control

7. Intravenous straight into blood, speed of injection varies, rapid for epileptic fits and asthma but slow for cytotoxic drugs.

   • Slow infucion gives fine controls on plasma levels
     • Method used by Drug abusers.

8. Inhalation, Local effects (bronchodilators), absorbed by lungs have large SA and good supply of blood easy access to blood stream

   • Rapid systemic effect.
     • Drugs of abuse= Nicotine and cannabis and glue sniffing

9. Topical (skin), Applied on skin and can have systemic effects, Steroid creams, nitroplasters(angina), Hyoscine patches(travel sick), Oestrogen for (HormReplceTherapy)

   • Nasal sprays and eye drops

10. Ways to cross membrane

    • Diffusion through lipids, diffuse through aqueous channels, carriers, pinocytosis of fluid droplets

11. Distribution

    • Solubility and ionisation affect distribution, Ionised stay in circulation and lipid soluble enter all tissue
      • pH and pKa affect ionisation of weak acid and base
      • Apparent Vol of dist= V(d) [L]= Dose (mg)/ Plasma conc(mg/L)
        • Examples, 70L means drug in whole body and if 5L then drug just in blood stream
        • Total exposure (if someone overdoses find out how badly they fucked up), Whold body burde/Dose (mg)= V(d)[L] X Plasma conc (mg/L)
    • Factors affecting rate of dist, Membrane permeability and blood perfusion.