Pharmacodynamics Flashcards
Pharmacodynamics
Effects of drugs on the body (or on microorganisms in the body); biochemical and physiological mechanisms of drug action and the relationship between drug concentration and effect.
Drugs act by binding receptors
“receptor” is a protein, which may be
- An enzyme
- Cell surface receptor (membrane protein)
- Nuclear receptor, which affects transcription of new mRNA/proteins in the nucleus of the cell.
Drugs act by binding receptors
A drug may be an agonist or antagonist.
- Agonist activates the receptor.
- Antagonist blocks/inhibits the receptor.
Enzymes
Proteins that catalyze (speed up) chemical reactions. End in -ase.
- Enzymes have active sites where their substrates bind.
- Inhibitors (antagonists) many bind…
- at the active site, mimicking substrates.
- away from the active site, but in a way that alters the active site.
Drug dose responses
- Phase 1: low drug dose.
- Phase 2: physiological response increases in proportion to # of receptors bound by the drug.
- Phase 3: receptors all bound/saturated with drug.
Drug dose responses: Phase 3: Plateau
More drug produces no/little further effect.
Therapeutic range
Range of plasma drug concentration above the level needed for therapeutic effect, below level of toxic effects.
- Often measured as therapeutic index.
- Want a high therapeutic index!
Drug efficacy
- Some drugs produce a larger effect than others - they are more effective.
- Mostly a factor for agonists (not antagonists).
Drug potency
How much drug is needed to give a response.
Tolerance
Decreased effect of a drug due to prolonged use.
Pharmacodynamic tolerance
- Number of drug receptors changes with time.
- Body/cells adapt to repeated stimulation. Eg. morphine.
Metabolic tolerance / enzyme induction
- Increased synthesis of cytochrome P450’s.
- Faster drug inactivation (liver cells adapt).
Drug dependence
When an individual has a strong compulsion to take a drug regardless of actual clinical need.
Physical dependence
Physically observable withdrawal symptoms.
Psychological dependence
Physically observed symptoms are not evident, but patient still has a convulsion to obtain the drug.
Drug interactions
- Taking two or more drugs at the same time may alter the effects of the drugs.
- Several ways this can happen, may result in increased or decreased drug effects.
- Additive or synergistic effects
- Competition for inactivation
- Enzyme induction
- Competition for serum albumin
Additive or synergistic effects
Two drugs that have similar effects individually may work together to create a larger effect.
- Helpful sometimes, eg antihypertensives.
- Harmful sometimes.
- Primary purposes of the drugs may be different.
Competition for inactivation
An isozyme may be busy/saturated inactivating one drug, so if a second one is added, t 1/2 of both increases.
- Mainly affects cytochrome P450 enzymes.
Enzyme Induction
• Opposite of competition for inactivation.
• Stimulation of cytochrome P-450 synthesis.
- Regular administration (several weeks) of some drugs stimulates the liver to make more drug metabolizing enzymes.
- higher level of enzymes results in faster inactivation of any drug using that CYP.
- Net effect: active levels of both drugs decrease.
Regular use of alcohol can cause induction of cytochrome P-450 isozymes which can result in faster drug metabolism.
- However chronic alcoholism can cause cirrhosis of the liver resulting in liver tissue death and lower liver enzyme levels.
- predicting the metabolic competency of a heavy drinker can be hard to predict.
Competition for serum albumin
• Non-polar drugs can compete for binding to serum albumin in blood transport.
- Net result: increased levels of available, unbound drug.
• Common drugs bound by albumin:
- warfarin (Coumadin)
- sulfonamides (antibiotics)
- digoxin (treatment of congestive heart failure)
- Dilantin (anti-seizure)
• When a second drug that binds to serum albumin is added to a patient on Coumadin, the Coumadin may be displaced from albumin and increase actual levels of active (non-protein bound) warfarin, causing greatly increased risk of bleeding and hemorrhage.
