WK2: PHARMACODYNAMICS

Pharmacodynamics = is the study of the effect of drugs on the body.

Drugs act within the body to mimic the actions of the body’s chemical messengers.
Dose-Response Relationship = is the body’s physiological response to changes in drug concentration at the site of action.
- Physiological = how organisms, organ systems, individual organs, cells, and biomolecules carry out chemical and physical functions in a living system
Potency – refers to the amount of drug needed to elicit a specific physiologic response to a drug.
Efficacy – the magnitude of effect a drug can cause when exerting its maximal effect.
Maximal efficacy – the point at which increasing a drug dosage no longer increases the desired therapeutic response
Therapeutic Index – (TI) describes the relationship between the therapeutic dose of a drug (ED50) and the toxic dose of a drug (TD50)
- Therapeutic dose of a drug – is the dose of a drug that produces a therapeutic response in 50% of the population.
- Toxic dose of a drug – is the dose that produces a toxic response in 50% of the population.

Parameters of Drug Action

If the ED50 and TD50 are close - drugs have a narrow therapeutic index. require close monitoring to ensure patient safety.
Onset – is the time it takes for a drug to reach the minimum effective concentration (MEC) after administration.
- Time from drug administration to first observable effect (T0-T1)
Peak – occurs when it reaches its highest concentration in the blood/plasma concentration. T0-T2
Duration of action – is the length of time the drug exerts a therapeutic effect. period from onset until the drug effect is no longer seen. T1-T3
Therapeutic Drug Monitoring
- Drug concentration can be determined by measuring peak and trough drug levels.
  - peak – highest plasma concentration. 30 minutes after infusion.
  - trough – lowest plasma concentration. 30 minutes before the next infusion

Theories of Drug Action

A. Drug-Receptor Interaction
- Certain portion of the drug molecule (active site) selectively combines with some molecular structure (reactive site) on the cell to produce a biological effect
  - Receptor site - drugs act at specific areas on cell membranes; react with certain chemicals to cause an effect within the cell
  - “Lock and Key Theory” - specific chemical (key) approaches a cell membrane and finds fit (the lock) at receptor site- affects enzyme
  - the system within the cell - produces certain effects.
    - Drug+Receptor=Effect
B. Drug-Enzyme Interaction
- Interferes with enzyme systems that act as catalysts from various chemical reactions
- If single step in one of enzyme system is blocked- normal function is disrupted
C. Nonspecific Drug Interaction
- Act by biophysical means that do not affect cellular/enzymatic reactions.
- drugs do not bind to receptors but instead saturate the water or lipid
- part of a cell - drug actions occur based on the degree of saturation.
  - Neutralization of stomach acid by antacids.
D. Selective Toxicity
- Specific action on cellular structures that are unique to the microbe.
- All chemotherapeutic agents would act only in one enzyme system needed for life of a pathogen or neoplastic cell.
- It is essential to the pathogen but not to the host.

B. Drug-Enzyme Interaction

DRUG RESPONSE

Primary - always desirable/physiologic effects
Secondary - desirable or undesirable
- Example: Diphenhydramine (Benadryl)
  - Primary effect: antihistamine; treat symptoms of allergy
  - Secondary: Drowsiness

Classification of Drug Action

Rapid - few seconds to minutes
- IV, SL, Inhalations
Intermediate- 1-2 hours after administration
- IM, SC
Delayed/Slow- several hours after administration
- Oral, rectal

Categories of Drug Action

Stimulation/Depression
- Stimulation - increased rate of cell activity/secretion from the gland
  - T3/T4 for hypothyroidism
- Depression - decreased cell activity and function of a specific organ.
  - Iodine, propylthiouracil
Replacement - replaces essential body compounds
- Example: Insulin
Inhibition/Killing of Organism
- ¡Interfere with bacterial cell growth
- ¡Example: Antibiotics
Irritation
- Example: Laxative- irritate the inner wall of colon---increased peristalsis-increased defecation

Drug-Drug Interaction

Additive Effect - 2 drugs with similar actions are taken for a doubled effect
- 1+1=2
- Ibuprofen + paracetamol= added analgesic effect
- Codeine with acetaminophen = better pain control
Synergistic - combined effect of 2 drugs is greater than the sum of the effect of each drug given alone; 1+1=3
- Aspirin = 30% analgesic effect
- codeine – 30% analgesic effect
- combination = 90% analgesic effect
Potentiation - a drug that has no effect enhances the effects of the second drug
- 0+1=2
- Alcohol enhances the analgesic activity of aspirin.
- Prozac + Zestril
Antagonistic - one drug inhibits the effect of another drug
- 1+1=0
- Tetracycline + antacid= decreased absorption of tetracycline
- Charcoal in alkaloidal poisoning

Adverse Drug Effects

Side Effects
- Results from the pharmacologic effects of the drug
- Most common as a result of lack of specificity of action within the therapeutic range.
Allergic Reactions
- Unpredictable adverse drug effects; more serious
- Response to patient’s immunological system to the presence of the drug
- Do not occur unless the patient has been previously exposed to the agent/chemical related compound
Idiosyncratic Reaction
- Occurs when the patient is first exposed to the drug
- Abnormal reactivity to the drug caused by a genetic difference between the patient and normal individual.
- a patient with G6PD deficiency will have anemia by using antioxidants.
Toxicity
- The degree to which a drug can be poisonous and thus harmful to the human body.
Iatrogenic responses
- Unintentional responses as a result of medical treatment
- Nephrotoxicity; ototoxicity

TERMINOLOGIES

● Pharmacodynamics - is the study of the effect of drugs on the body.
● Dose-Response Relationship - is the body’s physiological response to changes in drug concentration at the site of action.
● Potency - refers to the amount of drug needed to elicit a specific physiologic response to a drug.
● Efficacy - the magnitude of effect a drug can cause when exerting its maximal effect.
● Maximal efficacy – the point at which increasing a drug dosage no longer increases the desired therapeutic response.
● Therapeutic Index – (TI) describes the relationship between the therapeutic dose of a drug (ED50) and the toxic dose of a drug (TD50)
● Therapeutic dose of a drug – is the dose of a drug that produces a therapeutic response in 50% of the population.
● Toxic dose of a drug – is the dose that produces a toxic response in 50% of the population.
● Onset – is the time it takes for a drug to reach the minimum effective concentration (MEC) after administration.
● Peak – occurs when it reaches its highest concentration in the blood/plasma concentration. T0-T2
● Duration of action – is the length of time the drug exerts a therapeutic effect.
● Trough – lowest plasma concentration. 30 minutes prior to the next infusion.
● Additive Effect - Two drugs with similar actions are taken for a doubled effect
● Synergistic- combined effect of two drugs is greater than the sum of the effect of each drug given alone.
● Potentiation- a drug that has no effect enhances the effects of the second drug
● Antagonistic- one drug inhibits the effect of another drug
● Side Effects - results from the pharmacologic effects of the drug
● Allergic Reactions - unpredictable adverse drug effects; more serious
● Idiosyncratic Reaction - abnormal reactivity to the drug caused by a genetic difference between the patient and normal individual.
● Toxicity - the degree to which a drug can be poisonous and thus harmful to the human body.
● Iatrogenic responses - unintentional responses as a result of medical treatment