Administration and Absorption of Drugs

Factors that effect the action of a drug 1.Rate of accumulation at its site of action 2.Concentration of the drug at the site of action 3.The duration of the drug’s contact at those sites

Pharmocokinetics Refers to the movement of chemicals in a biological system This includes: –Administration and absorption –Distribution –Binding properties –Metabolic mechanisms –Elimination from the system

Administration of drugs To be effective a drug must enter the body and get to its site of action Best method of administration of a drug depends on the drug Most drugs dissolved in a fluid (saline) or contained in a mixture as in pills or capsules – type of substance is important Injections tend to be fast acting, oral administration is usually slow acting and of a longer duration

Routes of administration – Enteral routes Administered through the alimentary canal – oral or anal Common problem is that absorption rate can be highly variable –Absorption of orally administered drugs is greatly influenced by stomach contents –Hostile acid environment can interfere with absorption Other problems: –Some people cannot take pills –Uncooperative patients may refuse or “cheek” them

Routes of administration – Parenteral routes Injection –Intravenous – drug injected into vein Advantages – fastest way administer drug and dosage most accurate Disadvantages – chance of infection if conditions not sterile and no way to retrieve the drug in case of allergic or toxic reaction –Intramuscular – drug injected into muscle mass – slower but safer –Subcutaneous – injection under the skin or implanted under the skin –Direct injection in the nervous system

Routes of administration – Parenteral routes Pulmonary routes – inhalation into the lungs Topical routes – placing drug on the surface usually a surface with a mucous membrane –Sublingual – placed under the tongue –Intranasal – powder or liquid absorbed through mucous membrane in the nose –Skin – skin patches or topical anesthesia

Absorption of Drugs With the exception of drugs directly injected into the nervous system and topical anesthesia, drugs have to cross at least 2 membranes to reach its site of action –At a minimum, it has to cross into the blood stream, out of the blood stream, and into the cell Walls of blood vessels and cell membranes are semi-permeable

The bloodstream and drug movement How fast a drug gets into the bloodstream depends on route of administration Once in the blood, a drug has access to all types of tissue, muscle, fat skin, lungs, etc.

Structure of capillaries Capillaries in most of the body are made up of cells with gaps in between the cells These gaps allow some substances, but not blood cells of large proteins, to move in and out of the capillaries Some drug molecules will bind to these large proteins reducing the amount of “free” molecules in the blood When these free molecules leave the blood stream, bound molecules become unbound to maintain a stable concentration

Blood – brain barrier In the brain, the cells are more tightly packed so molecules have to move through the cells themselves – this makes up part of the blood-brain barrier Astrocytes make up the rest of the blood-brain barrier by sending out “feet” that help seal the capillary walls

Blood-brain barrier Very few substances can cross this barrier Membranes of the capillary cells and astrocytes are made up of lipids Only lipid soluble substances can be absorbed into the cells and pass through them This barrier important because the brain has no immune system

Movement across semi-permeable membranes Three types of fluid –Fluid in the bloodstream –Fluid outside the cells – extra cellular fluid –Fluid inside the cells – intracellular fluid These fluids can move back and forth across membranes Example thirst –Lack of fluid in blood –Extra cellular fluid moves into bloodstream –Intracellular fluid moves out of the cells –Loss of fluid detected; signal sent to drink

Movement across semi-permeable membranes Filtration – as fluid moves into a cell the membrane filters out large molecules which include many drug molecules Movement through diffusion – follows chemical gradient – chemicals flow from areas of high concentration to areas of low concentration –If a chemical is highly concentrated outside a cell, and openings exist, it will move into the cell

Placental Barrier A weak barrier between mother and fetus Large amounts of materials are exchanged between mother and fetus Most drugs easily cross the placental barrier – almost every drug a mother takes the fetus takes

Solubility Lipid soluble drugs – drugs that can be dissolved in lipids – fatty substances that make up cell membranes – including the blood-brain barrier Water soluble drugs – drugs that can dissolve in water – they will not passively move through a cell membrane so they require active transport