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PHARMACODYNAMICS




                   1
Pharmacologic Principles

Pharmacodynamics



• the study of drug concentration and its effect in the body.

    – WHAT THE DRUG DOES TO THE BODY




                                                                2
Pharmacodynamics

A positive change in a physiologic system is called a



             THERAPEUTIC EFFECT

       This is the goal of drug therapy



                                                        3
DRUG RESPONSE CAN CAUSE:


• PRIMARY EFFECT
  – the desirable effect; the immediate and first action of the
    drug producing one group of symptoms.

• SECONDARY EFFECT
  – maybe desirable or undesirable;
  – not primarily a drug effect and can be cause mainly by the
    organism’s reaction to the primary effect/action.




                                                                  4
Pharmacodynamics
Drugs exert their action on cells in 3 ways:

a) Receptor interactions
b) Enzyme interactions
c) Nonspecific interactions




                                               5
Pharmacodynamics
a) Receptor interactions

•   Key in a lock

•   Drug binds to a specific site on the cell
    (called a receptor site) and modifies the
    function of the cell

•   How many drugs work

•   How strong a drug binds to the receptor
    site is called the AFFINITY for that
    binding site




                                                6
Pharmacodynamics
a) Receptor interactions
•   AGONISTS
          Drugs that fit well at the receptor
            site and elicit desired
            action/function of the cell

            Mimics the substance that
             activates them


•   ANTAGONISTS
          Drugs that attach to the receptor
           site and block other drugs from
           attaching

            Blockers of receptor sites




                                                 7
Pharmacodynamics
a) Receptor interactions

•   Both Agonists and Antagonists are used in drug
    therapy

    – Albuterol inhaler- for asthma is an example of an agonist medicine

    – Benadryl ( diphenhydramine) is an antagonist.




                                                                           8
Pharmacodynamics
b) Enzyme interactions

    –   The drug alters the enzymes necessary for a
        certain body function

The Ace Inhibitor class of blood pressure medicines are an example of
   drugs that exert their action by altering enzyme pathways




                                                                        9
Pharmacodynamics
c) Non-specific interactions

           –alter the cell structure
           –alter some crucial cell process

Antibiotics are an example of drugs that alter the cell wall or
  alter the internal function of the bacterial cell




                                                                  10
Pharmacodynamics

   Once the drug is at the site of action, it can modify the
    rate (increase or decrease) at which the cells or tissues
    function

   A drug cannot make a cell or tissue perform a function it
    was not designed to perform




                                                                11
Pharmacodynamics
CATEGORIES OF DRUG ACTION

1. STIMULATION OR DEPRESSION of cell activity
• Stimulation= increases the rate of cell activity or the secretion from a gland;
• Depression=cell activity and function of a specific organ are reduced.

2. REPLACEMENT
• drugs that replace essential body compounds (e.g., insulin)

3. INHIBITION OR KILLING OF ORGANISMS
• drugs that interfere bacterial cell growth.

4. IRRITATION
• drugs that act as irritants to increase specific organ functions (e.g., laxative)




                                                                                      12
OTHER (TOXIC) EFFECTS OF DRUGS IN THE
                   BODY

1.SIDE EFFECTS
   – physiologic effects not related to the desired drug effects;
   – even with a correct drug dosage, side effects occur and are predicted.




                                                                          13
OTHER (TOXIC) EFFECTS OF DRUGS IN THE BODY

2. ADVERSE EFFECTS
   – more severe than slide effects;
   – unpleasant or even dangerous
   – can occur for a number of reasons:

   1.   The drug may have other effects on the body besides the therapeutic effect.

   2. The client is sensitive to the drug being given.

   3. The drug’s action in the body causes other responses that are undesirable or
       unpleasant.

   4. The client is taking too much or too little of the drug, leading to adverse
       effects.



                                                                                     14
OTHER (TOXIC) EFFECTS OF DRUGS IN THE
                  BODY


HYPERSENSIVITY

  – excessive responsiveness to either the primary or
    secondary effects of a drug;

  – may result from a pathologic or underlying
    condition.


                                                        15
DRUG ALLERGY
• causing an immune response when the person is exposed to the
  drug

Types:
1. ANAPHYLACTIC REACTION
     –   Antibody reacts with specific site in the body to cause the release of
         chemical.

2.   CYTOTOXIC REACTION
     –   antibodies that circulates in the blood and attacks antigen (the drug)
         on cell cite causing death of that cell;
     –   reaction is not seen immediately.




                                                                              16
DRUG ALLERGY
Types:

3. SERUM SICKNESS REACTON
   – Antibodies circulates in the blood and cause damage to various
     tissues by depositing in blood vessels
   – may occur after a week or more after the exposure to the drugs.

4. DELAYED ALLERGIC REACTION
   – occurs several hours after exposure and involves antibodies that
     are bound to specific WBC.




                                                                    17
DRUG INDUCED TISSUES AND ORGAN DAMAGE

1. DERMATOLOGIC REACTION
  –   adverse reaction in skin such as rashes, hives

  –   many drugs can be deposit in the skin or cause direct irritation
      to the tissue.

2. SUPER INFECTION
  –   several drugs like antibiotics, destroy the normal flora leading
      to the development of infection caused by the usually
      controlled organisms in the body.




                                                                         18
DRUG INDUCED TISSUES AND ORGAN DAMAGE

3. BLOOD DYSCRASIA
  – bone marrow suppression caused by drug effects;

  – occurs when drug that can caused cell death are used
    causing the rapidly multiplying bone marrow cells to die.




                                                                19
DRUG INDUCED TISSUES AND ORGAN DAMAGE

4. TOXICITY

   1. OTOTOXICITY
         •    damage to the cochlear and vestibular nerves causing deafness.


   2. HEPATOTOXICITY
         •    damage to the liver manifested by an increased in liver enzyme and failure of the liver to function.


   3. NEPHROTOXICITY
    – damage to the nephrons of the kidney causing kidney failure.

   4. CNS DEPRESSION
    – vital center of the body found in the central nervous system such as respiratory center is
      depressed manifested as changes in the rate and depth of breathing.




                                                                                                                     20
End




      21
Pharmacologic Principles

1)   Pharmaceutics
2)   Pharmacokinetics
3)   Pharmacodynamics
4)   Pharmacotherapeutics
5)   Pharmacognosy
6)   Toxicology



                                     22
Pharmacologic Principles

4) Pharmacotherapeutics

The use of drugs and the clinical indications for
 drugs to prevent and treat diseases




                                                    23
Pharmacotherapeutics
 Acute therapy-------- stroke, heart attack
 Maintenance therapy--- hypertension, hyperlipidemia,
 Supplemental/replacement therapy----insulin, iron, thyroid
 Palliative therapy--- high dose opioids for cancer patients,
 Supportive therapy—fluid and electrolytes, volume expanders
 Prophylactic therapy--- antibibiotics before surgery
 Empiric therapy– experience shows it works- no evidence-




                                                                 24
Pharmacotherapeutics
Therapeutic Drug Monitoring

• Certain drugs need close monitoring of blood levels during
  administration

• They have a potential to become toxic--
     some can become toxic at very low blood levels




                                                               25
Pharmacotherapeutics
Therapeutic Drug Monitoring
• The goal is to have enough drug in the body to get the positive
  desired effect--without producing undesirable adverse effects or
  toxicity. If the peak is too high, organ damage may result. If the
  trough is too low, the drug may not be at therapeutic levels

• Some drugs have a very narrow range between therapeutic and
  toxic

• Digoxin (heart med) and Gentamycin (antibiotic) are
  examples of drugs commonly monitored with blood levels




                                                                       26
Pharmacotherapeutics
Therapeutic Drug Monitoring

Peak Level
• Highest blood level


Trough Level
• Lowest blood level

• Blood is drawn at specfic times before and after drug
  administration--- the amount of the drug in the body guides the
  pharmacist in adjustment of drug dosages



                                                                    27
Pharmacotherapeutics

Monitoring

 The effectiveness of drug therapy must be evaluated
   –   Intended therapeutic action (beneficial)
   –   Unintended but potential adverse effects (predictable,
       adverse reactions)




                                                                28
Pharmacotherapeutics

Monitoring
    •   Therapeutic index
    •   Drug concentration
    •   Patient’s condition
    •   Tolerance and dependence
    •   Interactions
    •   Adverse drug effects



                                    29
Pharmacotherapeutics
MONITORING
 Therapeutic index
         Ratio of safety: the range between a drug’s therapeutic & toxic effects– a
          LOW therapeutic index means the drug has a greater chance of causing an
          adverse reaction
 Drug concentration
         Drug levels may become toxic if increased i.e.: renal/hepatic patients whose
          normal mechanisms for metabolism and excretion are compromised
 Patient’s condition
         Diseases and and other conditions such as stress and anxiety are just a few
          examples of conditons that can alter a patient’s response to drug therapy




                                                                                         30
Pharmacotherapeutics
MONITORING
 Tolerance
        a decreasing response to repeated doses

 Dependence
      a physiological or psychological need for a drug




                                                          31
Pharmacotherapeutics
Monitoring
• Interactions
        The alteration of the action of a drug by other substances

                   may occur with other drugs or food
                   Other prescribed drugs
                   Over-the-counter medications-
                   Herbal therapies
                   Certain foods

        Important to get a good nursing history of all drugs, herbs and
         problem foods that patient is taking

        Older patients are typically on multiple medications that may
         interact--- “polypharmacy”



                                                                           32
Pharmacotherapeutics
Monitoring
• Interactions
Drug interaction issues
    – Additive effect--smaller doses can be given with same effect ie.
      Tylenol and Codeine

    – Synergistic effect—2 drugs have a greater effect than either drug
      alone-- HCTZ with enalapril

    – Antagonistic effect--2 drugs have less of an effect than with
      either drug alone-- antacids with tetracycline-

    – Incompatibility—2 drugs mixed together and one or more
      deteriorates---furosemide and heparin




                                                                          33
Pharmacotherapeutics
Monitoring
Interactions
• Incompatibility- can be oral or IV drugs
 Focus for nurses when giving different IV drugs together

 Drugs may precipitate, become hazy, or change color when
  they are incompatible in the same IV tubing




                                                            34
Pharmacotherapeutics
Monitoring

Adverse Drug Events
 Potential hazards of medication use
          can be mild and minor
          can be life- threatening

 Two broad categories
       1. Medication errors
        2. Adverse drug reactions



                                        35
Pharmacotherapeutics

Monitoring
Adverse Drug Events

1. Medication errors
   Big focus in all health care areas today
   Can occur anywhere along the chain-
          prescriber, pharmacist, nurse, technician

       Medication errors are PREVENTABLE




                                                      36
Pharmacotherapeutics
Adverse drug reactions
Any reaction to a drug that is unexpected and undesirable that occurs at
     therapeutic doses

1.   Hypersensitivity (allergic) reaction


2.   Pharmacologic reactions
     Predictable, well-known reactions that result in little or no change in
     patient management
          -Predictable frequency
           Usually resolve when the drug is discontinued




                                                                               37
Pharmacotherapeutics

Contraindications to therapy

• Any characteristic of the patient, especially a disease
  state, that makes the use of a given medication
  dangerous for the patient

• It is important to assess for contraindications!




                                                            38
Pharmacotherapeutics
Contraindications to therapy
      • When the drug will be dangerous for the pt.

 Allergic to drug
 Pregnant
 Impaired liver or kidney function
 Wrong drug for the problem
 Many others



                                                      39
Pharmacologic Principles

5) Pharmacognosy

  The study of natural (plant and animal) drug
   sources




                                                 40
Pharmacologic Principles

5) Pharmacognosy

•   Four main sources for drugs
    1.   Plants
    2.   Animals
    3.   Minerals
    4.   Laboratory synthesis



                                        41
Pharmacologic Principles

5) Pharmacognosy
•   The source of all early drugs was from nature
            – Foxglove--cardiac drugs
            – Insulin– pigs and beef
            – aluminum hydroxide

•   Most new drugs are created synthetically in the lab
           – can be mass produced

•   We continue to discover many natural sources for drugs




                                                             42
Pharmacologic Principles

6) Toxicology

• The study of poisons and unwanted responses to drugs
  and other chemicals




                                                         43
Toxicology
 Drug Related Effects

 Teratogenic
     drugs or chemicals that result fetal defects
                Accutane


 Mutagenic
    drugs or chemicals that cause permanent changes in the genetic
    composition
                may pose a genotoxic hazard to hospital personnel or family
                members caring for the patient.


 Carcinogenic
      drugs, chemicals etc. that cause cancer
               Tobacco
               Tamoxifen


                                                                              44
Toxicology

    • http://toxicology.ucsd.edu/modules.htm




California Teratogen Information Service & Clinical Research Program
(800) 532-3749 (CA only),
UCSD Medical Center , Department of Pediatrics


                                                                       45

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PHARMA-PHARMACODYNAMICS

  • 2. Pharmacologic Principles Pharmacodynamics • the study of drug concentration and its effect in the body. – WHAT THE DRUG DOES TO THE BODY 2
  • 3. Pharmacodynamics A positive change in a physiologic system is called a THERAPEUTIC EFFECT This is the goal of drug therapy 3
  • 4. DRUG RESPONSE CAN CAUSE: • PRIMARY EFFECT – the desirable effect; the immediate and first action of the drug producing one group of symptoms. • SECONDARY EFFECT – maybe desirable or undesirable; – not primarily a drug effect and can be cause mainly by the organism’s reaction to the primary effect/action. 4
  • 5. Pharmacodynamics Drugs exert their action on cells in 3 ways: a) Receptor interactions b) Enzyme interactions c) Nonspecific interactions 5
  • 6. Pharmacodynamics a) Receptor interactions • Key in a lock • Drug binds to a specific site on the cell (called a receptor site) and modifies the function of the cell • How many drugs work • How strong a drug binds to the receptor site is called the AFFINITY for that binding site 6
  • 7. Pharmacodynamics a) Receptor interactions • AGONISTS  Drugs that fit well at the receptor site and elicit desired action/function of the cell  Mimics the substance that activates them • ANTAGONISTS  Drugs that attach to the receptor site and block other drugs from attaching  Blockers of receptor sites 7
  • 8. Pharmacodynamics a) Receptor interactions • Both Agonists and Antagonists are used in drug therapy – Albuterol inhaler- for asthma is an example of an agonist medicine – Benadryl ( diphenhydramine) is an antagonist. 8
  • 9. Pharmacodynamics b) Enzyme interactions – The drug alters the enzymes necessary for a certain body function The Ace Inhibitor class of blood pressure medicines are an example of drugs that exert their action by altering enzyme pathways 9
  • 10. Pharmacodynamics c) Non-specific interactions –alter the cell structure –alter some crucial cell process Antibiotics are an example of drugs that alter the cell wall or alter the internal function of the bacterial cell 10
  • 11. Pharmacodynamics  Once the drug is at the site of action, it can modify the rate (increase or decrease) at which the cells or tissues function  A drug cannot make a cell or tissue perform a function it was not designed to perform 11
  • 12. Pharmacodynamics CATEGORIES OF DRUG ACTION 1. STIMULATION OR DEPRESSION of cell activity • Stimulation= increases the rate of cell activity or the secretion from a gland; • Depression=cell activity and function of a specific organ are reduced. 2. REPLACEMENT • drugs that replace essential body compounds (e.g., insulin) 3. INHIBITION OR KILLING OF ORGANISMS • drugs that interfere bacterial cell growth. 4. IRRITATION • drugs that act as irritants to increase specific organ functions (e.g., laxative) 12
  • 13. OTHER (TOXIC) EFFECTS OF DRUGS IN THE BODY 1.SIDE EFFECTS – physiologic effects not related to the desired drug effects; – even with a correct drug dosage, side effects occur and are predicted. 13
  • 14. OTHER (TOXIC) EFFECTS OF DRUGS IN THE BODY 2. ADVERSE EFFECTS – more severe than slide effects; – unpleasant or even dangerous – can occur for a number of reasons: 1. The drug may have other effects on the body besides the therapeutic effect. 2. The client is sensitive to the drug being given. 3. The drug’s action in the body causes other responses that are undesirable or unpleasant. 4. The client is taking too much or too little of the drug, leading to adverse effects. 14
  • 15. OTHER (TOXIC) EFFECTS OF DRUGS IN THE BODY HYPERSENSIVITY – excessive responsiveness to either the primary or secondary effects of a drug; – may result from a pathologic or underlying condition. 15
  • 16. DRUG ALLERGY • causing an immune response when the person is exposed to the drug Types: 1. ANAPHYLACTIC REACTION – Antibody reacts with specific site in the body to cause the release of chemical. 2. CYTOTOXIC REACTION – antibodies that circulates in the blood and attacks antigen (the drug) on cell cite causing death of that cell; – reaction is not seen immediately. 16
  • 17. DRUG ALLERGY Types: 3. SERUM SICKNESS REACTON – Antibodies circulates in the blood and cause damage to various tissues by depositing in blood vessels – may occur after a week or more after the exposure to the drugs. 4. DELAYED ALLERGIC REACTION – occurs several hours after exposure and involves antibodies that are bound to specific WBC. 17
  • 18. DRUG INDUCED TISSUES AND ORGAN DAMAGE 1. DERMATOLOGIC REACTION – adverse reaction in skin such as rashes, hives – many drugs can be deposit in the skin or cause direct irritation to the tissue. 2. SUPER INFECTION – several drugs like antibiotics, destroy the normal flora leading to the development of infection caused by the usually controlled organisms in the body. 18
  • 19. DRUG INDUCED TISSUES AND ORGAN DAMAGE 3. BLOOD DYSCRASIA – bone marrow suppression caused by drug effects; – occurs when drug that can caused cell death are used causing the rapidly multiplying bone marrow cells to die. 19
  • 20. DRUG INDUCED TISSUES AND ORGAN DAMAGE 4. TOXICITY 1. OTOTOXICITY • damage to the cochlear and vestibular nerves causing deafness. 2. HEPATOTOXICITY • damage to the liver manifested by an increased in liver enzyme and failure of the liver to function. 3. NEPHROTOXICITY – damage to the nephrons of the kidney causing kidney failure. 4. CNS DEPRESSION – vital center of the body found in the central nervous system such as respiratory center is depressed manifested as changes in the rate and depth of breathing. 20
  • 21. End 21
  • 22. Pharmacologic Principles 1) Pharmaceutics 2) Pharmacokinetics 3) Pharmacodynamics 4) Pharmacotherapeutics 5) Pharmacognosy 6) Toxicology 22
  • 23. Pharmacologic Principles 4) Pharmacotherapeutics The use of drugs and the clinical indications for drugs to prevent and treat diseases 23
  • 24. Pharmacotherapeutics  Acute therapy-------- stroke, heart attack  Maintenance therapy--- hypertension, hyperlipidemia,  Supplemental/replacement therapy----insulin, iron, thyroid  Palliative therapy--- high dose opioids for cancer patients,  Supportive therapy—fluid and electrolytes, volume expanders  Prophylactic therapy--- antibibiotics before surgery  Empiric therapy– experience shows it works- no evidence- 24
  • 25. Pharmacotherapeutics Therapeutic Drug Monitoring • Certain drugs need close monitoring of blood levels during administration • They have a potential to become toxic-- some can become toxic at very low blood levels 25
  • 26. Pharmacotherapeutics Therapeutic Drug Monitoring • The goal is to have enough drug in the body to get the positive desired effect--without producing undesirable adverse effects or toxicity. If the peak is too high, organ damage may result. If the trough is too low, the drug may not be at therapeutic levels • Some drugs have a very narrow range between therapeutic and toxic • Digoxin (heart med) and Gentamycin (antibiotic) are examples of drugs commonly monitored with blood levels 26
  • 27. Pharmacotherapeutics Therapeutic Drug Monitoring Peak Level • Highest blood level Trough Level • Lowest blood level • Blood is drawn at specfic times before and after drug administration--- the amount of the drug in the body guides the pharmacist in adjustment of drug dosages 27
  • 28. Pharmacotherapeutics Monitoring  The effectiveness of drug therapy must be evaluated – Intended therapeutic action (beneficial) – Unintended but potential adverse effects (predictable, adverse reactions) 28
  • 29. Pharmacotherapeutics Monitoring • Therapeutic index • Drug concentration • Patient’s condition • Tolerance and dependence • Interactions • Adverse drug effects 29
  • 30. Pharmacotherapeutics MONITORING  Therapeutic index  Ratio of safety: the range between a drug’s therapeutic & toxic effects– a LOW therapeutic index means the drug has a greater chance of causing an adverse reaction  Drug concentration  Drug levels may become toxic if increased i.e.: renal/hepatic patients whose normal mechanisms for metabolism and excretion are compromised  Patient’s condition  Diseases and and other conditions such as stress and anxiety are just a few examples of conditons that can alter a patient’s response to drug therapy 30
  • 31. Pharmacotherapeutics MONITORING  Tolerance  a decreasing response to repeated doses  Dependence  a physiological or psychological need for a drug 31
  • 32. Pharmacotherapeutics Monitoring • Interactions The alteration of the action of a drug by other substances  may occur with other drugs or food  Other prescribed drugs  Over-the-counter medications-  Herbal therapies  Certain foods Important to get a good nursing history of all drugs, herbs and problem foods that patient is taking Older patients are typically on multiple medications that may interact--- “polypharmacy” 32
  • 33. Pharmacotherapeutics Monitoring • Interactions Drug interaction issues – Additive effect--smaller doses can be given with same effect ie. Tylenol and Codeine – Synergistic effect—2 drugs have a greater effect than either drug alone-- HCTZ with enalapril – Antagonistic effect--2 drugs have less of an effect than with either drug alone-- antacids with tetracycline- – Incompatibility—2 drugs mixed together and one or more deteriorates---furosemide and heparin 33
  • 34. Pharmacotherapeutics Monitoring Interactions • Incompatibility- can be oral or IV drugs Focus for nurses when giving different IV drugs together Drugs may precipitate, become hazy, or change color when they are incompatible in the same IV tubing 34
  • 35. Pharmacotherapeutics Monitoring Adverse Drug Events  Potential hazards of medication use can be mild and minor can be life- threatening  Two broad categories 1. Medication errors 2. Adverse drug reactions 35
  • 36. Pharmacotherapeutics Monitoring Adverse Drug Events 1. Medication errors Big focus in all health care areas today Can occur anywhere along the chain- prescriber, pharmacist, nurse, technician Medication errors are PREVENTABLE 36
  • 37. Pharmacotherapeutics Adverse drug reactions Any reaction to a drug that is unexpected and undesirable that occurs at therapeutic doses 1. Hypersensitivity (allergic) reaction 2. Pharmacologic reactions Predictable, well-known reactions that result in little or no change in patient management -Predictable frequency Usually resolve when the drug is discontinued 37
  • 38. Pharmacotherapeutics Contraindications to therapy • Any characteristic of the patient, especially a disease state, that makes the use of a given medication dangerous for the patient • It is important to assess for contraindications! 38
  • 39. Pharmacotherapeutics Contraindications to therapy • When the drug will be dangerous for the pt.  Allergic to drug  Pregnant  Impaired liver or kidney function  Wrong drug for the problem  Many others 39
  • 40. Pharmacologic Principles 5) Pharmacognosy The study of natural (plant and animal) drug sources 40
  • 41. Pharmacologic Principles 5) Pharmacognosy • Four main sources for drugs 1. Plants 2. Animals 3. Minerals 4. Laboratory synthesis 41
  • 42. Pharmacologic Principles 5) Pharmacognosy • The source of all early drugs was from nature – Foxglove--cardiac drugs – Insulin– pigs and beef – aluminum hydroxide • Most new drugs are created synthetically in the lab – can be mass produced • We continue to discover many natural sources for drugs 42
  • 43. Pharmacologic Principles 6) Toxicology • The study of poisons and unwanted responses to drugs and other chemicals 43
  • 44. Toxicology Drug Related Effects  Teratogenic drugs or chemicals that result fetal defects Accutane  Mutagenic drugs or chemicals that cause permanent changes in the genetic composition may pose a genotoxic hazard to hospital personnel or family members caring for the patient.  Carcinogenic drugs, chemicals etc. that cause cancer Tobacco Tamoxifen 44
  • 45. Toxicology • http://toxicology.ucsd.edu/modules.htm California Teratogen Information Service & Clinical Research Program (800) 532-3749 (CA only), UCSD Medical Center , Department of Pediatrics 45