Unit 1: DRUG ACTION

THREE PHASES OF DRUG ACTION  Order without first pass effect: absorption >>
distribution >> metabolism/biotransformation
1. Pharmaceutic
>> excretion
2. Pharmacokinetic
 Order with first pass effect: absorption >> >>
3. Pharmacodynamic
metabolism/biotransformation >> distribution
I. PHARMACEUTIC PHASE
>> excretion
 Drug becomes a solution to cross biologic
1. Absorption
membrane
 Movement of drug particles from GI tract to
 80% of drugs are taken by mouth.
body fluids by:
 Tablets undergo disintegration and a. Passive absorption – does not require energy
dissolution. to move across the membrane
 Tablets are not 100% pure drug. b. Active absorption – requires a carrier (enzyme
 Excepients – fillers and inert substances used or protein) to move the drug particles
to allow drug to take on a particular size and c. Pinocytosis – drug particles are engulfed by
shape and to enhance drug dissolution. cells and carry it across the membrane; drugs
 Disintegration – breakdown of tablet into that are lipid soluble and unbound are easily
smaller particles. absorbed.
 Dissolution – dissolving of smaller particles in
Gastrointestinal fluid. First Pass Effect or Hepatic First Pass
 Rate limiting – the time it takes the drug to  The drug in oral form passes to the liver first
disintegrate and dissolve for availability of before it can be used by the body.
absorption.  This deactivates or metabolizes medication
1 Intravenous fastest to be absorbed  Examples:
(IV) o Morphine sulfate – opioid analgesic;
2 Intramuscular (1) Deltoid usually for those with myocardial
(IM) (2) Gluteus maximus infarction (MI); it decreases the pain
3 Subcutaneous slower compared to IM & of the patient; it suppresses
(SubQ) IV; used for slow regimen respiration and may cause respiratory
intended to release slowly depression
ex.: Insulin – for a slow o warfarin (Coumadin) – anticoagulant;
release and slow given to patient post MI; it can
normalization of blood
prevent the formation of new,
sugar (!!) not given in SubQ
existing clots
in diabetic ketoacidosis
-only regular insulin can Bioavailability – the percentage of drug that reaches
given in IV in emergency the systemic circulation.
situations
4 Suppositories,  Oral – less than 100%
Otic, and  Intravenous solution – almost always 100%;
others directly absorbed in the body
5 Oral It takes about 20 mins. to  Drugs with hepatic first pass – 20%-40% only
be absorbed because it passes the portal circulation and is
deactivated by the liver
II. PHARMACOKINETIC PHASE
Passage of drugs through plasma membrane:
 process of drug movement to achieve drug
action. a. Diffusion or Passive Transport
 “What your body does to the drug”
b. Active Transport – movement of solute or acid, creatinine, and water
particle against a concentration or molecules)
electrochemical gradient. o Those that cannot pass through:
2. Distribution (RBCs, proteins, and albumins)
 The drug becomes available to body fluids  Glomerular filtration rate – the amount of
and tissues which are influenced by blood substances filtered out from the glomerulus
flow, affinity to tissue and protein binding of the nephrons. Normal rate is 125mL/min.
effect (albumin – protein that maintains Every minute, 1 mL of urine and 124 mL are
the oncotic/osmotic pressure in the blood cleansed and returned to the body.
vessels, a protein that holds fluid inside the  Creatinine clearance – the amount of
blood vessels). creatinine filtered by the glomerulus in one
 Drugs that are active, free, unbound, and minute.
no affinity to other cells in the body can  Creatinine – most reliable indicator of
serve its purpose kidney function; a waste product of muscle
 Drugs that stick, adhere, or cling to albumin metabolism by the creatine phosphate in
or protein can be inactive (unfree drug); the muscle. Slightly higher in males than in
these cannot serve their purpose females because of larger muscle mass in
o Highly protein bound – 89% and males.
above  Decreased GFR and Creatinine clearance
o Moderately highly protein bound increase the accumulation of waste product
– 61%-89% and drug metabolites in the body leading to
o Moderately protein bound – 30%- toxicity.
60% III. PHARMACODYNAMIC PHASE
o Low protein bound – 30% and  Study of drug concentration and its effect on
below the body
3. Metabolism or Biotransformation  “what the drug does to your body”
 Process of building up or breaking down  Drugs have primary and secondary effect
drug particles in the body. (which is desirable or undesirable)
 Liver – primary site  Example: Diphenhydramine (Benadryl)
 Decreased metabolism of drug increases its
Primary Treat symptoms of allergy
concentration in the body.
Effect
 Half-life (t1/2) – the time it takes for one-half
Secondary Drowsiness; CNS
of the drug concentration to be eliminated. Effect depression
4. Excretion or Drug Elimination Undesirable When taken during driving,
 Kidneys – main route; filter free, unbound, working and operating
water-soluble and unchanged drugs. machineries
 Drugs that are water soluble are easily Desirable When taken at bedtime
filtered.  Example: Cetirizine (Loratidine) –
 Fat-soluble drugs: easier to absorb in antihistamine
stomach but hard to excrete
Primary Treat symptoms of allergy
 Lungs – eliminate volatile drug substances
Effect
 GFR & Creatinine clearance should be
Secondary Drowsiness; CNS
assessed. Effect depression
 Glomerulus – filtration unit of kidney; semi- Undesirable When taken during driving,
permeable; only those that can pass the working and operating
fenestration of the glomerulus can be machineries
filtered Desirable When taken at bedtime
o Example: small molecules that can
pass through glomerulus (urea, uric
Dose Response – relationship between the minimal
versus the maximal amount of drug dose needed to
produce the desired drug response
Onset of Action – the time it takes the drug to reach
the minimum effective concentration
Peak Action – the highest blood or plasma drug
concentration
Duration of Action – the length of time the drug has
pharmacologic effect
Time – response curve; evaluates the parameters of
drug action: onset, peak, and duration of action.
Receptor Theory
Receptors
 Protein in structure that can be found in the cell
membrane
 Receptors are locks that need keys in the form
of drugs, hormones, or enzymes to open it and
let those cells that their receptors are opened
to act on their purposes or uses in the body.
Agonist – drug that opens the receptor site and
produced a response that let the cell do its purpose.
Example: Albuterol acts on Beta-2 receptor to produce
a response of BRONCHODILATION.
Antagonist – drug that opens the receptor site and
produces a response opposite to the specific purpose of
the cell.
Example: Esmolol (breviblock) – a beta receptor blocker
that blocks Beta 1 receptor to lower the heart rate and
blocks Beta 2 receptor to produce a response of
BRONCHOCONSTRICTION.
Non-Specific Drugs – drugs that affect various sites of
receptor and have properties of non-specificity.
Example: Bethanechol (urecholine)
 produce micturition in clients with urinary
retention
 it also constricts pupils, decrease the heart rate,
lowers blood pressure, increase gastric
secretion and causes bronchoconstriction
 it stimulates cholinergic receptors
Non-selective drugs – affects two or more receptors
Example: antidepressant drugs which act on dopamine,
norepinephrine and serotonin receptors.
Drug plasma concentration and therapeutic response
 The therapeutic response of a drug is directly
related to their plasma level
A. Minimum effective concentration (MEC) -
amount of drug required to produce a
therapeutic effect
B. Toxic concentration (TC) - Level of drug that
will result in serious adverse reaction.
C. Therapeutic range - Plasma drug
concentration between MEC and TC
Therapeutic Index – estimates the margin of safety of
a drug
1. Low therapeutic index
o Has a narrow margin of safety
o The dosage needs adjustment.
o Serum (plasma) drug levels needs to be
monitored routinely.
o Small safety range between effective
dose and lethal dose.
2. High therapeutic index
o Has a wide margin of safety.
o Less danger of producing toxic effects.
Peak drug level
 The highest plasma concentration of a drug at
specific time.
 Indicates the rate of absorption.
Trough drug level
 The lowest plasma concentration of a drug.
 Indicates the rate of elimination.
Loading dose
 A large initial dose which is use to have an
immediate drug response.
 After it has been given, a prescribed dose per
day is given.
 Higher amount of drug is given once to prime
the blood stream with a sufficient level of drug
therapeutic response
Maintenance dose - A dose that is given to keep
plasma drug concentration within the therapeutic
range.
Side effects - Physiologic effects which is not related to
the desired drug effects. They can be desirable or
undesirable.
Adverse reaction - More severe effects which are not
related to the desired drug effects and always
undesirable.
Toxic effects or toxicity - It can be identified by  Vary from person to person in response to
monitoring the serum (plasma) therapeutic range of the given medication.
drug.  Pharmacogenomics – explores the individual’s
unique response to drug based on genetic
Pharmacogenetics - The effect of drug action varies
makeup.
according to genetic factors and hereditary influences
7. Immunologic factors
of a person taking the medication.
 People can develop an allergy to drug due to
Tachyphylaxis - Drug tolerance to a frequently immune response of a person to medication
repeated administration of drug. Ex. Opioid analgesics, given.
barbiturates, minor tranquilizers etc.  First drug exposure – development of
antibodies specific to react on medication
Placebo effect - Psychologic benefit from a compound given.
that may not have the chemical structure of drug.  Second drug exposure – produce an allergic
Critical concentration - The amount of a drug that is reaction.
needed to cause a therapeutic effect.
8. Psychological factors
Dynamic equilibrium - Balance of drug movement  Person’s attitude towards drug, affect how the
reaching the body to form concentration for action drug works.
involving the four processes of pharmacokinetic phase.  Ex. Placebo effect
Blood brain barrier 9. Environmental factors
 Protective system of cellular activity that keeps  A quiet, cool, and non - stimulating
many things away from CNS. Ex. poisons, environment assist the sedated client to relax
bacteria etc. and fall asleep.
 Lipid soluble drugs can pass the blood brain 10. Tolerance
barrier. 11. Cumulation
 Ex. Dexamethasone (decadron)  An instance wherein the medication has been
Placenta & breastmilk accumulated inside the body leading to toxicity
 Medication may pass through the placenta and and adverse effect
affect the developing fetus of pregnant women.  Factors: doses at intervals that is shorter than
recommended.
FACTORS INFLUENCING DRUG EFFECTS o The body doesn’t eliminate the
1. Weight medication
 Heavy people = larger doses.
 Light weight people = smaller doses.
2. Age
 Pediatrics – calculation of age, weight and body
surface area to get the exact dose.
3. Gender
 Men – IM injections – the effects are seen
sooner.
 Women – subcutaneous injections with fat
depositing drugs – slowly released to the body.
4. Physiological factors
 Varies from person to person how their body
react and handles medications.
5. Pathological factors
 The presence of 2 or more diseases in one
person can change the pharmacokinetics of
medications.
 Ex. GI disorders affect the absorption of drugs
6. Genetic factors