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PHARMACOKINETICS



              MERLYN A.
       BARACLAN, RN, RMT
pharmacokinetics
 Definition:
- refers on how the body acts on the drug


- involves the study of absorption,
  distribution, metabolism
  (biotransformation) and drug excretion
I. Overview
 Aim of drug therapy
- To prevent, cure or control various disease
  states
                 adequate drug doses must be
  delivered to the target tissues

          so that therapeutic yet NON – toxic
  levels are obtained
Overview
 Too much of a drug will result into toxic
  effects & too little will not result into the
  desired therapeutic effects.
4 Fundamental Pathways of Drug Movement &
Modification in the Body
      Drug at the site of Administration

                1 . ABSORPTION
                     (INPUT)

    Drug in plasma
                          2. DISTRIBUTION
                  drug in tissues
                         3. METABOLISM
                    metabolites in tissues

                           4. ELIMINATION
                               (OUTPUT)
         Drug & metabolites in urine, feces, or bile
II. Routes of Drug
Administration
- Determined primarily
  by the properties of the
  drug

2 MAJOR ROUTES OF
   DRUG
   ADMINISTRATION
1. Enteral
2. Parenteral
ENTERAL routes
                 A. ORAL
                 B. SUBLINGUAL




                 C. RECTAL
PARENTERAL routes

IV / intravascular


                                              IM /
                                         intramuscular



                     SC / subcutaneous
parenteral
 Advantages                     Disadvantages
 Fast: 15–30 seconds for IV,    more risk of addiction
  3–5 minutes for IM and            when it comes to injecting
  subcutaneous (SC)                 drugs of abuse
 100% bioavailability             Belonephobia, the fear of
                                    needles and injection.
 suitable for drugs not           If needles are shared, there
  absorbed by the gut or            is risk of HIV and other
  those that are too irritant       infectious diseases
  (anti-cancer)                    It is the most dangerous
                                    route of administration
 IV can deliver continuous        If not done properly,
  medication, e.g., morphine        potentially fatal air boluses
  for patients in continuous        (bubbles) can occur.
  pain, or saline drip for         Need for strict asepsis
  people needing fluids
Parenteral
 Used for drugs which are
    poorly absorbed in the
    GIT
   Unstable drugs
   For unconscious patients
   Circumstances that
    require a rapid onset of
    action
   Provides the most
    control over the actual
    dose delivered to the
    body
Routes of Drug
Administration
 1. ENTERAL
A. ORAL
- most common route of administration
- Most variable
- most complicated pathway
- Cheapest
- Non - invasive
[NOTE: most drugs are absorbed in the GIT &
   encounter the liver before they are distributed
   into the general circulation]
Routes of Drug
Administration
 1. Enteral
B. SUBLINGUAL
- Placement under the tongue
- Allows the drug to diffuse into the capillaries
  & therefore to enter the systemic circulation
Advantage: the drug bypasses the intestine &
  liver & thus avoids 1st pass metabolism
Routes of Drug
   Administration
1. Enteral
c. Rectal
- Useful if the drug induces vomiting if given orally or
    if the patient is already vomiting
- Drainage of the rectal region bypasses the portal
   circulation
- Similar to the sublingual route, it prevents the
   destruction of the drug by intestinal enzymes or by
   the low pH in the stomach
[note: commonly used to administer anti – emetic
   agents]
Routes of Drug Administration
 2. Parenteral
a. IV / intravascular
- IV injection is the most
 common parenteral route
- For drugs which are not absorbed orally
- Bypasses the liver
- Permits a rapid effect and a maximal degree of
    control over the circulating levels of the drug
- Can introduce bacterial contamination at the site
- Can cause hemolysis
Routes of Drug Administration
2. Parenteral
b. IM / intramuscular
                          aqueous sol’n
Drugs administered
                        specialized depot
                          preparations
Routes of Drug Administration
2. Parenteral
c. SC / subcutaneous
- This route of
   administration like IM
   requires absorption &
   somewhat slower than
   the IV route
Routes of Drug Administration
 3. Others
a. Inhalation
- Provides a rapid
    delivery of a drug
    across a large surface
    area of the mucus
    membranes of the
    respiratory and the
    pulmonary epithelium
- Effect is as rapid as IV
    injection
- For gaseous drugs
 Advantages
 Fastest method, 7–10
  seconds for the drug to
  reach the brain

 Disadvantages
 Typically a more addictive
  route of administration
  because it is the fastest,
  leading to instant
  gratification.
 Difficulties in regulating
  the exact amount of
  dosage
 Patient having difficulties
  administering a drug via
  inhaler
Routes of Drug Administration

               3. Others
               b. Intranasal
               - Through the nose


               eg. : desmopressin,
                 salmon calcitonin,
                 cocaine
Routes of Drug Administration
. Others
c. Intrathecal, intraventricular
- Introducing drugs directly into
   the cerebrospinal fluid / CSF
Eg., amphotericin B
Routes of Drug Administration
               3. Others
              d. Topical
              - Is used when a local effect
                 of a drug is required



              - Eg., clotrimazole, atropine
Routes of Drug Administration
3. Others
e. Transdermal
- This route of administration
   achieves systemic effects by
   application of drugs to the
   skin, usually by using a
   transdermal patch.
- Rate of absorption varies
   markedly
- Eg., nitroglycerin
III. ABSORPTION OF
DRUGS
 Is the transfer of a drug
  from its site of
  administration to the
  bloodstream

 IV delivery – absorption
  is complete
III. ABSORPTION OF DRUGS
 A. Transport of Drug
  from the GIT
1. PASSIVE DIFFUSION
- The driving force for
    passive absorption of a   - Does not involve a carrier
    drug is the               - Vast majority of drugs
    concentration gradient      gain access to the body
- The drug moves from a         by this mechanism
    region of high
    concentration to one of
    a lower concentration
III. ABSORPTION OF DRUGS
     2. Active Transport
     - Involves a specific carrier protein


     - Is “energy dependent” & is driven by the
       hydrolysis of ATP

     - Also capable of moving a drug against a
       concentration gradient
III. ABSORPTION OF DRUGS
B. Physical Factors Influencing Absorption



1. Blood flow to the absorption site

2. Total surface area available for absorption

3. Contact time at the absorption surface
IV. Bioavailability



     - Refers to the fraction of an
       administered drug that reaches the
       systemic circulation
V. Drug                   - Affected by the following
                            factors:
Distribution

                          - 1. Blood Flow
- Is the process by
                          - 2. Capillary permeability
  which a drug
  reversibly leaves the          capillary structure
  bloodstream &                  blood brain barrier
  enters the              - 3. Binding of Drugs to
  interstitium              proteins
  (extracellular fluid)
  and / or the cells of
  the tissues.
VI. Binding of Drugs to Plasma
  Proteins        A. Binding capacity of
 Bound drugs are                albumin
 pharmacologically        -      Reversible
 INACTIVE, only the
 FREE, UNBOUND drug         low capacity     high capacity
 can act on target sites
 in the tissues, elicit a
 biologic response & be
                          Note : ALBUMIN has the
 available to the             strongest affinity for ANIONIC
 processes of                 DRUGS & HYDROPHOBIC
 elimination                  DRUGS.
VII. DRUG METABOLISM
 Drugs are often
  eliminated by
  biotransformation and
  or excretion into the
  URINE OR BILE.

 LIVER – the MAJOR
  SITE FOR DRUG
  METABOLISM
Reactions of Drug Metabolism
 The kidney cannot
  efficiently eliminate      PHASE I
  lipophilic drugs ,
  therefore lipid soluble
  agents must 1st be
  metabolized in the liver
  using 2 general sets of
  reactions
                             PHASE II
Phase I
 Converts lipophilic
  molecules into more
  polar molecules

 Phase I metabolism
  may increase,             Often uses the P 450
  decrease, or leave          system
  unaltered the drug’s
  pharmacologic activity.
Phase II

 Consists of conjugation      The highly polar drug
  reactions                     conjugates may then
 Uses substrates like          be excreted by the
  glucuronic acid, sulfuric     kidney or bile
  acid, acetic acid, or an
  amino acid
 Renders the
  metabolites INACTIVE
  and more water soluble
DRUG ELIMINATION
 Removal of a drug         Drugs that have been
  from the body may          made water soluble in
   occur via a number of     the liver are often
   routes, the most          readily excreted in the
   important being the       kidneys.
   kidney or urine          Kidney dysfunction can
 Other routes:              lead to toxic levels of
- bile, intestine, lung,     the drug in the body
   milk,                     because the drug
                             cannot be excreted.
Thank you       Self-respect
for             is the fruit of
                discipline; the
listening!!!    sense of
                dignity grows
                with the ability
                to say no to
                oneself.

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Pharmacokinetics ppt

  • 1. PHARMACOKINETICS MERLYN A. BARACLAN, RN, RMT
  • 2. pharmacokinetics  Definition: - refers on how the body acts on the drug - involves the study of absorption, distribution, metabolism (biotransformation) and drug excretion
  • 3. I. Overview  Aim of drug therapy - To prevent, cure or control various disease states adequate drug doses must be delivered to the target tissues so that therapeutic yet NON – toxic levels are obtained
  • 4. Overview  Too much of a drug will result into toxic effects & too little will not result into the desired therapeutic effects.
  • 5. 4 Fundamental Pathways of Drug Movement & Modification in the Body Drug at the site of Administration 1 . ABSORPTION (INPUT) Drug in plasma 2. DISTRIBUTION  drug in tissues 3. METABOLISM metabolites in tissues 4. ELIMINATION (OUTPUT) Drug & metabolites in urine, feces, or bile
  • 6. II. Routes of Drug Administration - Determined primarily by the properties of the drug 2 MAJOR ROUTES OF DRUG ADMINISTRATION 1. Enteral 2. Parenteral
  • 7. ENTERAL routes A. ORAL B. SUBLINGUAL C. RECTAL
  • 8. PARENTERAL routes IV / intravascular IM / intramuscular SC / subcutaneous
  • 9. parenteral  Advantages  Disadvantages  Fast: 15–30 seconds for IV,  more risk of addiction 3–5 minutes for IM and when it comes to injecting subcutaneous (SC) drugs of abuse  100% bioavailability  Belonephobia, the fear of needles and injection.  suitable for drugs not  If needles are shared, there absorbed by the gut or is risk of HIV and other those that are too irritant infectious diseases (anti-cancer)  It is the most dangerous route of administration  IV can deliver continuous  If not done properly, medication, e.g., morphine potentially fatal air boluses for patients in continuous (bubbles) can occur. pain, or saline drip for  Need for strict asepsis people needing fluids
  • 10. Parenteral  Used for drugs which are poorly absorbed in the GIT  Unstable drugs  For unconscious patients  Circumstances that require a rapid onset of action  Provides the most control over the actual dose delivered to the body
  • 11. Routes of Drug Administration  1. ENTERAL A. ORAL - most common route of administration - Most variable - most complicated pathway - Cheapest - Non - invasive [NOTE: most drugs are absorbed in the GIT & encounter the liver before they are distributed into the general circulation]
  • 12. Routes of Drug Administration  1. Enteral B. SUBLINGUAL - Placement under the tongue - Allows the drug to diffuse into the capillaries & therefore to enter the systemic circulation Advantage: the drug bypasses the intestine & liver & thus avoids 1st pass metabolism
  • 13. Routes of Drug Administration 1. Enteral c. Rectal - Useful if the drug induces vomiting if given orally or if the patient is already vomiting - Drainage of the rectal region bypasses the portal circulation - Similar to the sublingual route, it prevents the destruction of the drug by intestinal enzymes or by the low pH in the stomach [note: commonly used to administer anti – emetic agents]
  • 14. Routes of Drug Administration 2. Parenteral a. IV / intravascular - IV injection is the most common parenteral route - For drugs which are not absorbed orally - Bypasses the liver - Permits a rapid effect and a maximal degree of control over the circulating levels of the drug - Can introduce bacterial contamination at the site - Can cause hemolysis
  • 15. Routes of Drug Administration 2. Parenteral b. IM / intramuscular aqueous sol’n Drugs administered specialized depot preparations
  • 16. Routes of Drug Administration 2. Parenteral c. SC / subcutaneous - This route of administration like IM requires absorption & somewhat slower than the IV route
  • 17. Routes of Drug Administration 3. Others a. Inhalation - Provides a rapid delivery of a drug across a large surface area of the mucus membranes of the respiratory and the pulmonary epithelium - Effect is as rapid as IV injection - For gaseous drugs
  • 18.  Advantages  Fastest method, 7–10 seconds for the drug to reach the brain  Disadvantages  Typically a more addictive route of administration because it is the fastest, leading to instant gratification.  Difficulties in regulating the exact amount of dosage  Patient having difficulties administering a drug via inhaler
  • 19. Routes of Drug Administration 3. Others b. Intranasal - Through the nose eg. : desmopressin, salmon calcitonin, cocaine
  • 20. Routes of Drug Administration . Others c. Intrathecal, intraventricular - Introducing drugs directly into the cerebrospinal fluid / CSF Eg., amphotericin B
  • 21. Routes of Drug Administration  3. Others d. Topical - Is used when a local effect of a drug is required - Eg., clotrimazole, atropine
  • 22. Routes of Drug Administration 3. Others e. Transdermal - This route of administration achieves systemic effects by application of drugs to the skin, usually by using a transdermal patch. - Rate of absorption varies markedly - Eg., nitroglycerin
  • 23. III. ABSORPTION OF DRUGS  Is the transfer of a drug from its site of administration to the bloodstream  IV delivery – absorption is complete
  • 24. III. ABSORPTION OF DRUGS  A. Transport of Drug from the GIT 1. PASSIVE DIFFUSION - The driving force for passive absorption of a - Does not involve a carrier drug is the - Vast majority of drugs concentration gradient gain access to the body - The drug moves from a by this mechanism region of high concentration to one of a lower concentration
  • 25. III. ABSORPTION OF DRUGS 2. Active Transport - Involves a specific carrier protein - Is “energy dependent” & is driven by the hydrolysis of ATP - Also capable of moving a drug against a concentration gradient
  • 26. III. ABSORPTION OF DRUGS B. Physical Factors Influencing Absorption 1. Blood flow to the absorption site 2. Total surface area available for absorption 3. Contact time at the absorption surface
  • 27. IV. Bioavailability - Refers to the fraction of an administered drug that reaches the systemic circulation
  • 28. V. Drug - Affected by the following factors: Distribution - 1. Blood Flow - Is the process by - 2. Capillary permeability which a drug reversibly leaves the  capillary structure bloodstream &  blood brain barrier enters the - 3. Binding of Drugs to interstitium proteins (extracellular fluid) and / or the cells of the tissues.
  • 29. VI. Binding of Drugs to Plasma Proteins A. Binding capacity of  Bound drugs are albumin pharmacologically - Reversible INACTIVE, only the FREE, UNBOUND drug low capacity high capacity can act on target sites in the tissues, elicit a biologic response & be Note : ALBUMIN has the available to the strongest affinity for ANIONIC processes of DRUGS & HYDROPHOBIC elimination DRUGS.
  • 30. VII. DRUG METABOLISM  Drugs are often eliminated by biotransformation and or excretion into the URINE OR BILE.  LIVER – the MAJOR SITE FOR DRUG METABOLISM
  • 31. Reactions of Drug Metabolism  The kidney cannot efficiently eliminate PHASE I lipophilic drugs , therefore lipid soluble agents must 1st be metabolized in the liver using 2 general sets of reactions PHASE II
  • 32. Phase I  Converts lipophilic molecules into more polar molecules  Phase I metabolism may increase, Often uses the P 450 decrease, or leave system unaltered the drug’s pharmacologic activity.
  • 33. Phase II  Consists of conjugation  The highly polar drug reactions conjugates may then  Uses substrates like be excreted by the glucuronic acid, sulfuric kidney or bile acid, acetic acid, or an amino acid  Renders the metabolites INACTIVE and more water soluble
  • 34. DRUG ELIMINATION  Removal of a drug  Drugs that have been from the body may made water soluble in occur via a number of the liver are often routes, the most readily excreted in the important being the kidneys. kidney or urine  Kidney dysfunction can  Other routes: lead to toxic levels of - bile, intestine, lung, the drug in the body milk, because the drug cannot be excreted.
  • 35. Thank you  Self-respect for is the fruit of discipline; the listening!!! sense of dignity grows with the ability to say no to oneself.