Psychopharmacology -- Pharmacology

Pharmacokinetics (PK)

• Movement of drugs

• how the body acts on drugs

Pharmacodynamics (PD)

• Power of drugs

• How drugs act on the body

PK: Describe ADME(T)

Absobtion

Distribution

Metabolism

Elimination/excretion

Toxicity

NOTE: all these factors are influenced by body weight

• dose

• body fluid

Forms of Administration - PK

• oral

• inhalation

• transdermal

• intranasal

• sublingual

• injection

Oral

• The drug must be soluble and stable in the stomach fluid 

• Food in the stomach will slow down “passing”

  • Delayed absorption and decreased maximum drug level achieved 

• About 75% absorbed in 2 - 3 hours 

  • Slow 

• Advantages 

  • Safest

  • easier to give a measured, specific dose

  • Slow 

• Disadvantages

  • Slow 

  • Occasional vomiting or stomach distress

  • Unpredictable absorption rate

  • Some drugs are destroyed by stomach acid 

• Caveat: crushing tablets - consider dangers and alternate routes

Inhalation

• Probably 2nd most popular method 

• Faster than oral 

• Why would inhalation be faster than oral 

  • Goes straight to your lungs, then to your bloodstream very quickly

  • Your brain needs oxygen, so it also goes to your brain quickly

Transdermal

• Skin Patches

• Advantages

  • Alternative to oral (no gastrointestinal side effects)

  • Increased penetration at sites with greater cutaneous blood flow

  • Extended release 

• Limitations/Disadvantages

  • Skin is a strong barrier (the drug must be able to penetrate skin)

Sublingual

• (mucous membranes)

  • Chemicals can enter the bloodstream more easily

• Advantages 

  • Fast acting - efficient and quick absorption

  • Does not irritate the stomach and cause vomiting 

• Disadvantages

  • Unpleasant taste of drugs - not used much 

Injection and Types

• Advantages 

  • One of the fastest absorption rates (but depends on type)

• Disadvantages

  • Sterile conditions necessary 

  • Danger of too much drug administration (over-dose)

  • Painful 

Types

• Subcutaneous (SC)

  • under the skin

• Intravenous (IV)

  • Into the vein (quickest!!)

• Intramuscular (IM)

  • Into the muscle

PK - Distribution

• To understand absorption from the blood → brain, we have to know about two concepts

1. Lipid solubility

   1. Lipophilic drugs (like lipids - AKA: fat), take much longer ot reach the site of action 

      1. Cannabis 

      2. alchohol

2. The Blood-Brain-Barrier (BBB)

   1. Not an actual wall, but a structural concept, providing a gatekeeper function

      1. A line of cells at the brain → determines what can enter the brain and what cannot

   2. Psychoactive drugs must penetrate the BBB to reach sites of action

Some drugs can diffuse through the BBB

Metabolism - PK

Metabolism 

• Definition → to break down 

• To become deactivated, a drug must:

  • Be excreted from the body or be chemically changed 

• LIVER and KIDNEY: the primary organs in drug metabolism and the elimination of the drug

Liver and Kidney (metabolism)

• Liver breaks down circulating drugs, and the metabolites are then carried in the bloodstream to the kidneys, where they might remain in the urine for excretion 

  • First-pass metabolism 

• Enzymes – proteins that break down and metabolize drugs

  • Specialty enzymes in the liver are called liver microsomal enzymes

  • Lack of specificity – also breaks down toxins in food and environmental pollutants 

• Your kidney eliminates water, so your kidneys can get rid of water if the drug is water-soluble

• If it is fat-solubl,e the kidneys will not excrete it → it will go back into the kidneys and keep trying to get it in water soluble form 

Metabolite

• The metabolite no longer has the same action as the drug 

  • Usually 

• The metabolite is more likely to be excreted by the kidneys 

• Metabolites may be 

  • Inactive !!

  • Active

    • And may even be as active as the original chemical, known as the parent compound 

• Prodrugs - pharmacologically inactive, but their metabolites are active 

  • Chemotherapeutic drugs

  • L-DOPA (to treat parkinson’s disease)

• Summary 

  • Steps in the sequence of elimination and breakdown

  • Blood → hepatic artery → liver, metabolizes to by-products → returned ot bloodstream → kidney 

  • ****metabolite****

Tolerance - PK

• What might be the effect of chronic exposure to a drug on the total amount of enzymes in the liver 

  • Enzyme levels would increase 

• What would the impact of that have on metabolism 

  • Metabolism would increase

• What would be necessary to maintain the same amount of the drug in the body

  • Drug intake would have to increase 

• Metabolic Tolerance 

Excretion - PK

• Major route of drug elimination

  • Kidneys and urine

• Lungs - exhaling 

  • Not every chemical can be breathed out 

  • EX → alcohol (breathalyzer)

• Skin - sweating 

  • You can sometimes smell alcohol on a person

• Fecal matter 

Eliminaiton

• Process and rate are typically described by 2 laws of kinetics 

  • Zero order (LINEAR)

    • A constant amount of drug is eliminated per unit time, and that is independent of the concentration in the blood 

    • Example: alcohol will be metabolized and eliminated at a constant rate no matter how much has been ingested 

  • First-order (EXPONENTIAL)

    • Refers to the process whereby the rate of elimination is proportional to the amount of drug in the body, i.e, the larger the quantity of a drug, the faster the body “tries” to get rid of it

    • The majority of drugs are eliminated in this way