1. Drug Actions and Interactions
Chapter 10
Drug Actions and Interactions
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2. Overview Two or more drugs can alter the effect of each other
Complete, current medication records must be maintained for patients
Many problems occur from drug interactions

3. Pharmacokinetics
Pharmacokinetics is the study of drugs within the body
It includes the mechanisms of:
Drug absorption
Drug distribution
Drug metabolism
Drug excretion

4. Pharmacokinetics

5. Drug Absorption
Absorption - movement of a drug from site administration into the bloodstream
Diffusion – moving from areas of higher concentration to areas of lower concentration
First-pass effect - oral drugs mostly absorbed in small intestine, partly metabolized in liver

6. Drug Distribution
Process by which drug molecules leave the bloodstream and enter the tissues of the body
Rate of distribution is highly dependent on the blood flow to various organs

7. Drug Metabolism
Most drugs undergo metabolism, and are converted to metabolic derivatives (biotransformation)
The enzyme called cytochrome P-450 is very important in drug metabolism

8. Drug Excretion Process by which drugs are eliminated from the body
The kidney is the major site of excretion
Drugs are mostly excreted in the urine, followed by the feces, saliva, sweat, breast milk, breath, and tears

9. Pharmacodynamics
Pharmacodynamics – the study of biochemical and physiological effects of drugs
It is also the study of the mechanism of action of drugs

10. Drug Action
Specific affinity – a drug “chooses” a certain cell and exerts its effects
Receptor – the specific cell recipient
Agonist – the drug that has specific affinity for this cell, which it functionally changes

11. Drug Action

12. Drug Half-Life
Half-life – the time needed for plasma concentration of a drug to be reduced by 50%
Bioavailability – measurement of drug absorption and total amount of drug reaching systemic blood circulation after administration

13. Diurnal Body Rhythms Diurnal – “during the day”
Important in the effects of certain drugs
Example – sedatives should be given before bedtime, not in the morning

14. Psychological Factors
People respond to prescribed drugs differently, based on how they feel about them
Placebo – a simulated medication that contains no active ingredients
A patient who believes in a placebo may report actual beneficial drug effects

15. Drug Toxicity
Therapeutic index – the range between a drug’s therapeutic and toxic doses
This is expressed in a ratio:
LD50 / ED50
LD50 = lethal dose that will kill 50% of animals tested
ED50 = effective dose that will produce a specific therapeutic effect in 50% of animals tested

16. Drug Effects Side effects – mild, annoying responses to a drug
Adverse effects – more severe symptoms in response to a drug
Idiosyncratic reaction – a unique, strange, or unpredicted reaction to a drug

17. Hypersensitivity or Allergy
Hypersensitivity reactions – unpredictable reactions, usually after a patient has received a drug and developed antibodies against it
Antigen-antibody reaction produces itching, hives, rash, or skin swelling

18. Anaphylactic Reaction
Anaphylactic reaction – a severe form of allergic reaction that is life-threatening
Signified by shortness of breath and sometimes, cardiac collapse
It is a true medical emergency

19. Drug Interaction
An interference of a drug with the effect of another drug, nutrient, or laboratory test
Usually from taking more than one drug concurrently
Can occur during liberation, absorption, distribution, biotransformation, or excretion

20. Synergism
“Working together” of two or more drugs to produce a stronger effect than for each drug taken alone
Example: the combination of warfarin sodium with aspirin, which causes excessive risk of blood hemorrhage

21. Potentiation One drug prolongs the effects of another drug
Is often desirable in order to build up a sufficient drug level or to prolong its effect
Example: when cimetidine is combined with asthma medications containing theophylline

22. Antagonism Two drugs decrease the effects of each other
Example: when ibuprofen and aspirin are taken together, they stop each other’s action
Tetracycline and antacids should not be used together since tetracycline must be absorbed in the stomach and antacids inhibit this

23. Multiple Pharmacological Effects
Many current drugs can influence many physiological systems
Example: combining antipsychotics, antidepressants, and antiparkinsonian drugs causing unanticipated additive anticholinergic effect

24. Multiple Prescribers
Seeing multiple physicians makes it difficult for each to be aware of all drugs prescribed to the patient
Example: antihistamines from one physician mixed with antianxiety drugs from another may cause an excessive depressant effect

25. Nonprescription Drug Use
Patients may not mention nonprescription medications to their physicians
Interactions with prescription drugs can occur
Purchase both prescription and nonprescription medications at the same pharmacy

26. Patient Noncompliance
Many patients do not take medication in the manner intended by the prescriber because of:
Confusion about dosage instructions
Forgetting to take all of their various medications
After forgetting to take a dose, many patients double the next dose

27. Drug Abuse
Drug abuse or deliberate misuse drugs may cause increased drug interactions
Opioids, barbiturates, analgesics, and amphetamines are drugs most often abused

28. Patient Variables Affecting Drug Interaction
Age
Genetic factors
Diseases and conditions
Diet
Alcohol consumption
Smoking

29. Age
Young and elderly patients have increased incidence of adverse drug reactions
Cytochrome P-450 (enzymes) contribute to many drug interactions in newborns
Elderly patients’ illnesses and slowing of renal function increases interactions

30. Genetic Factors
Control rate of metabolism for isoniazid, which may cause peripheral neuritis
Isoniazid may inhibit metabolism of phenytoin, causing nystagmus, ataxia, and lethargy

31. Diseases and Conditions
Impaired renal and hepatic function are the most important conditions that alter drug activity
Renal and hepatic diseases influence patient responses to certain drugs

32. Diet Food can affect drug absorption from the GI tract
Many antibiotics must be given one hour before, or two hours after meals
Grapefruit juice interacts with estrogens, cyclosporine, midazolam, triazolam, and all calcium channel blockers
(continues)

33. Diet
Toxicity of some drugs (such as MAO inhibitors) increases with wine, cheese, or yogurt
CNS-stimulating drugs may cause toxicity if combined with caffeine
Potassium-sparing diuretics and salt substitutes can cause dangerous blood potassium levels

34. Alcohol Consumption
Chronic use may affect metabolism of drugs such as warfarin, phenytoin, and tolbutamide
If used concurrently with sedatives and depressants, can cause excessive depressant response

35. Smoking Increases activity of drug-metabolizing liver enzymes
This can decrease effects of diazepam, theophylline, chlorpromazine, and amitriptyline

36. Reducing Risk of Drug Interactions
Patient risk factors: age, medical condition, diet, smoking, alcohol use
Accurate patient drug history required
Knowledge of drug actions is essential in assessing drug interactions
Use therapeutic alternatives instead of drugs that can interact (continues)

37. Reducing Risks of Drug Interactions
Avoid complex therapeutic regimens; keep number of medications to a minimum
Educate patients about their illnesses and benefits and risks of their drug therapy