DRUGS and the BODY

To understand what happens when a drug is administered the nurse must understand
“Pharmacodynamics and Pharmacokinetics

Pharmacodynamics:

 Pharmacodynamics is the branch of Pharmacology that deals with the study of

mechanism of drug action.
 The mechanism of drug action describes both where the interaction (drug's target site)
takes place and how the change (therapeutic response) occurs.
 How the drugs works on the body.

Drugs Usually Works In One Of Four Ways:

1. To replace or act as substitute for missing chemicals.
2. To increase or stimulate certain cellular activities
3. To depress or slow cellular activities.
4. To interfere with the functioning of foreign cells.

1. To replace or act as substitute for missing chemicals.

 Insulin is a chemical messenger that allows cells to absorb glucose, a sugar, from
the blood.
 The pancreas is an organ behind the stomach that is the main source of insulin in
the body.
2. To increase or stimulate certain cellular activities
 Adrenaline in your bloodstream achieves its effects on your heart rate by
stimulating the adrenergic receptors on cells throughout your heart tissue. Once
stimulated, these receptors pass the fight-or-flight message to a specialized type
of protein called a G-protein. The result is Cardiac stimulation and
hyperglycemia.
3. To depress or slow cellular activities
 Tachycardia is the term for a heart rate that's faster than normal ― more than
100 beats per minute
  Normal Heart Rate
 60 – 100 beats per minute
4. To interfere with the functioning of foreign cells
 Immunosuppressant stops your immune system from damaging healthy cells and
tissues.
 People with organ transplants and stem cell transplants take these medicines to
prevent transplant rejections.
 The drugs also treat autoimmune disease symptoms.

Drugs Can Act In Several Different Ways To Achieve These Results.

 Receptor Sites
 Drugs-Enzymes Interactions
 Selective Toxicity

A. Receptor Sites
 The interaction between the chemical and the receptor site affects enzyme
system within the cell.
 The activated enzyme system then produce certain effect such as increase or
decrease cellular activity, change in cell membrane permeability or alteration in
cellular metabolism

Mechanism of Action
 Understanding the Mechanism of Action or how a medication functions within
the body, is essential to understanding the processes medications go through to
produce the desired effect.
Drugs Have Agonistic or Antagonistic Effects.
 A drug agonist binds tightly to a receptor to produce a desired effect.
 A drug antagonist competes with other molecules and blocks a specific action or
response at a receptor site

Two Types of Drug-Receptor Interactions

- When a drug binds to receptor, several therapeutic consequences can result. A
specific activity of the cell is either enhanced or inhibited.

1. AGONIST (Mimic Ligand-Receptor Activation Responses)

 A drug that produces a stimulation type response.
  Very close mimic to the ligand.
 Therefore: it ‘Fits’
2. ANTAGONIST (Block the Receptor’s Activation Response)
 A drug that binds to the receptor and blocks the biological response for that
receptor.
TYPES of ANTAGONIST
 Competitive Antagonist- binds to the same site as the agonist but does not
activate it
 Noncompetitive Antagonist- binds to an allosteric (non-agonist) site on the
receptor to prevent activation of the receptor.

Pharmacodynamics - “How the drugs works on the body”

For example:
 Inhibition of platelet aggregation after administering Aspirin
 The reduction of blood pressure after ACE inhibitors
 The blood-glucose-lowering effect of Insulin.

EFFICACY versus POTENCY

 EFFICACY
o Measure of the maximal therapeutic response that the drug is able to produce.
 POTENCY
o Measure of the amount of drug necessary to produce a therapeutic response.

B. Drug-Enzyme Interaction
 Drug-enzyme interaction is similar to drug receptor interaction. The drugs resemble the
natural substrates, bind enzymes and cause change in their activity.
 Drugs also can cause their effects by interfering with the enzyme systems that act as a
catalyst for various chemical reactions.
 Enzyme system work in a cascading fashion with one enzyme activating another enzyme
activating another- until a cellular reaction eventually occurs.
 If a single step in one of the many enzyme system is blocked, normal cell function is
disrupted.

Example:

 Proton pump inhibitors inhibit the hydrogen potassium ATPase in parietal cells of
stomach, thus inhibit HCl secretion.
  These are used to treat depression. They inhibit the monoamino oxidase enzyme which
breaks down catecholamines. Thus decreased levels of noradrenalin and serotonin are
coped by MAO inhibitors and increased levels are achieved

C. Selective Toxicity
 Selective toxicity, which means that the drug is harmful to a pathogen without being
harmful to the host.
 An ideal antimicrobial agent exhibits selective toxicity, which means that the drug is
harmful to a pathogen without being harmful to the host.

PHARMACOKINETICS
Different drugs have different ways in which they enter the body and attack the base for an
illness or diseases. The pharmacokinetic process is concerned with the absorption, distribution
and elimination of drugs. In the Pharmacology class we got to learn more on pharmacokinetics

Pharmacokinetics

o Refers to the way the body handles drugs.

o How the body work on the drug.
o It is the branch of pharmacology which deals with the four processes - A.D.M.E.

 Absorption
 Distribution
 Metabolism
 Excretion
1. Absorption
 Refers to the passage of medication molecules into the blood from the site of
administration.
 Refer to what happens to a drug from the time it introduce (enters) to the body till it
reaches the circulating fluids (bloodstream) and fluids.
 When a drug is released from its formulation/administration site and enters the
bloodstream.
Factors Affecting Absorption
 Route of administration
 Ability of medication to dissolve
 Blood flow to the area of absorption
 Contact time at the absorption surface
  Body surface area available for absorption
 Lipid solubility of a medication

Route of Administration
 Generally, drugs given by oral route are absorbed slowly than those given parentally.
 Parenteral route – drugs administered via Intravenous (IV) are absorbed the fastest.
 Oral route – most frequently used route, less expensive, non –invasive and safest way
to deliver drug.

Factors Affecting Absorption

Route of administration Factors Affecting Absorption
IV (intravenous)  None: direct entry into the blood stream/venous
system
IM (intramuscular)  Perfusion or blood flow to the muscle
 Fat content of the muscle
 Temperature of the muscle: cold causes
vasoconstriction and decreases absorption: heat
causes vasodilation and increases absorption.
Sub-Q (subcutaneous  Perfusion or blood flow to the tissue
 Fat content of the tissue
 Temperature of the tissue: cold causes
vasoconstriction and decreases absorption: heat
causes vasodilation and increases absorption
PO (oral)  Acidity of the stomach
Entry of meds through  Length of time in the stomach
mouth  Blood flow to the GIT
 Presence of interacting foods or drugs.
PR (rectal  Perfusion or blood flow to the rectum
 Lesion in the rectum.
 Length of time retained for absorption
Mucous membrane  Perfusion or blood flow to the area
( sublingual, buccal,  Integrity of mucous membrane
Translingual)  Presence of food or smoking
 Perfusion or blood flow to the area
Topical (skin)  Integrity of the skin
 Perfusion or blood flow to the area
Inhalation  Integrity of lung lining
 Ability to administer drug property

First Pass Effect

  The first pass effect (also known as first-pass metabolism or pre systemic metabolism) is
a phenomenon of drug metabolism whereby the concentration of a drug, specifically
when administered orally, is greatly reduced before it reaches the systemic circulation.
 It is the fraction of drug lost during the process of absorption which is generally related
to the liver and gut wall.
 The portal vein delivers these absorbed molecules into the liver which immediately
transform most of the chemicals delivered to it by a series of liver enzymes.
o These enzymes break the drug into metabolites.
o Some metabolite is active and causes an effect in the body.
o Some metabolite are deactivated and excreted from the body.
o Large percentage of oral dose is destroyed – never reached the tissue. This
phenomenon is called FIRST PASS EFFECT.

3. Distribution

 Distributed within the body tissues and organs and ultimately to its specific site of
action (leave the bloodstream and enters the ECF and or cells)
 Depends on physical and chemical properties of meds and physiology of person
taking the meds (e.g. blood flow, capillary permeability, degree of binding of the
drug to tissue proteins hydrophobicity.

Factors affecting distribution

A. Circulation/blood flow

 Depends on vascularity of various tissue and organs on how fast it reaches the site.

Example: solid tumors have poor blood supply and may not respond to therapy intended to
destroy them

 Blood flow varies: greater in the brain, liver and kidneys than skeletal muscles; least in
adipose tissue
 In obese patients; blood flows through fat slowly = increase time before the drug is
released

B. Membrane permeability / capillary permeability (barriers to drug

distribution)

 Must pass all of the biological membranes an organ/tissue has

Depends on:
  Drug structures: hydrophobic vs. Hydrophilic drugs
 Capillary structure
o Brain : continuous and no slit junctions; cells are physically joined ( tight
junctions) forming a wall (BBB) = prevent entry of substances
o Blood Brain Barrier – allows only fat-soluble meds (lipid soluble drugs readily
penetrate the CNS since they can dissolve in the membrane of the endothelial
o Liver and spleen: large discontinuous capillaries, large fenestration = allow
drugs to exchange freely between blood
o Placental barrier: nonselective barrier to drugs.

C. Protein binding to drugs

 When meds binds to albumin, they cannot exert any pharmacological activity. The
unbound or “free” meds is the active form of medication.
 Plasma albumin: Major drug binding protein and act as drug reservoir (as concentration
of free drug decreases due to elimination, the bound drug dissociates from the albumin
= 1 concentration and hence prolong period of drug action)
 Example:
o Older adults – 1 albumin
o liver disease -1 albumin
 Because of potential for more meds being unbound, 1 risk formed activity or toxicity or
both

3. Metabolism

Drug metabolism or Biotransformation

 Metabolism describes the chemical reactions that change drugs into compounds which
are easier to eliminate.
 Liver – most important site of drug metabolism or biotransformation.
 Biotransformation
– The process by which drugs are changed into new, less active chemicals.
- is the process by which the body changes a drug from its dosage form to a more
water-soluble form that can then be excreted.

Drugs can be metabolized in several ways:

 Most drugs are metabolized into inactive metabolites ( product of metabolism or
necessary for metabolism) which are then excreted.
  Other drugs are converted to active metabolites, which are capable of exerting their
own pharmacologic action.
 Most drugs are metabolized into inactive metabolites (product of metabolism or
necessary for metabolism) which are then excreted.
 Other drugs are converted to active metabolites, which are capable of exerting their
own pharmacologic action
 Biotransformation occurs under influence of enzymes that detoxify, degrade and
remove biologically active chemicals wherein most occur within the liver although this
can also happen in the kidneys, lungs, blood and intestine.
o Decrease liver function (rich in enzyme system such as cytochrome P450) meds
eliminated more slowly resulting in meds accumulation and risk for drug toxicity.

Metabolisms are affected by the following factors:

 Age – infants and elderly has reduced ability to metabolize some drugs.
 Nutrition – liver enzymes involved in metabolism rely on adequate amounts of amino
acid, lipids, and carbohydrates.
 Hormones - Insulin/adrenal corticosteroids can reduce metabolism of drugs in the liver

4. Excretion

 Process by which drugs are eliminated through the body

(lungs, kidney, GIT, breast milk, salivary glands, sweat glands)
 After the drug is metabolized, it exits the body through the kidneys, bowel, lungs and
exocrine glands.
 Route of excretion- kidney via urine (most common), bile, intestine, lungs, milk and
dialysis.

Half-life (T1/2)

 The time it takes a drug to lose half its original concentration or activity after being
introduced into the body. Drug half-life is considered when determining drug dosing.
 A medication's biological half-life refers simply to how long it takes for half of the dose
to be metabolized and eliminated from the bloodstream. Or, put another way, the half-
life of a drug is the time it takes for it to be reduced by half.
https://www.verywellmind.com/medication-half-life.

O LORD my God, I cried unto thee, and thou hast healed me.

Psalms 30:2 KJV