Pharmacology

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Pharmacology
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Ideal Drug

• Effectiveness
• Safety
• Selectivity
• Reversible
• Predictability
• Ease of administration
• Freedom from drug interactions

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Ideal Drug

• Low cost
• Chemical Stability
• Possession of a simple generic name

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Therapeutic Objective

• Maximum benefit with minimum harm
• The intensity of the response to a drug is
  directly related to the concentration of the drug
  at its site of action

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Intensity of Drug responses

• Administration dosage and route
• Pharmacokinetics
• Pharmacodynamics
• Individual variation

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Nursing Responsibilities

• Last line of defense against errors!!!!!!!!!
• Patient education
• Utilize the nursing process

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Drug Legislation

• 1906 drugs should be free of adulterants
• 1938 testing for toxicity
• 1962 proof of effectiveness
• 1970 Controlled Substance Act Scheduled drugs
• 1997 Food and Drug Administration Modernization
  Act

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New Drug Development

• Preclinical testing prior to testing on humans
• Clinical testing
• I normal volunteers except maybe patients who
  have disease
• II and III patients
• IV released for general use

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• Be neither the first to adopt the new nor the
  last to abandon the old!

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Drug Names

• Chemical
• Generic Name
• Trade Name
• OTC drugs

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Pharmacokinetics

• Drug movement throughout the body
• Absorption movement of drug from its site of
  administration into blood
• Dissolve must dissolve before being absorbed
• Surface area the larger the faster
• Blood flow most rapid where blood flow is high
• Lipid solubility - the higher the faster
• pH partitioning

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Absorption - Routes

• IV no barriers to absorption
• Intramuscular good for poorly soluble drugs,
  time released
• Subcutaneous again no significant barriers
• Oral must pass through cells of epithelium,
  enteric coating
• Safer but highly variable absorption enteric,
  sustained-release, tablets

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Routes of Drug Administration

• Robert L. Copeland, Ph.D.
• Department of Pharmacology
• www.med.howard.edu/pharmacology
• 202.806.6311

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Drug Absorption

• Absorption is the process by which a drug enters
  the bloodstream without being chemically altered
  or
• The movement of a drug from its site of
  application into the blood or lymphatic system

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Drug Absorption

• Factors which influence the rate of absorption
• types of transport
• the physicochemical properties of the drug
• protein binding
• routes of administration
• dosage forms
• circulation at the site of absorption
• concentration of the drug

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Drug Absorption

• The rate at which a drug reaches it site of
  action depends on
• Absorption - involves the passage of the drug
  from its site of administration into the blood
• Distribution - involves the delivery of the drug
  to the tissues

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Drug Absorption

• Mechanisms of solute transport across membranes
• passive diffusion
• filtration and bulk flow
• endocytosis
• ion-pairing
• active transport
• Drug Absorption animation

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Ion Trapping cont
Body fluids where a pH difference from blood pH
will favor trapping or reabsorption stomach
contents small intestine
breast milk
aqueous humor (eye)
vaginal secretions
prostatic secretions
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Ion Trapping

• Kidney
• Nearly all drugs filtered at the glomerulus
• Most drugs in a lipid-soluble form will be
  absorbed by passive diffusion.
• To increase excretion change the urinary pH to
  favor the charged form of the drug
• Weak acids excreted faster in alkaline pH
  (anion form favored)
• Weak bases excreted faster in acidic pH (cation
  form favored)

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Lipid-Water Partition Coefficient

• The ratio of the concentration of the drug in two
  immiscible phases a nonpolar liquid or organic
  solvent (representing the membrane) and an
  aqueous buffer, pH 7.4 (representing the plasma)

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Lipid-Water Partition Coefficient

• The higher the lipid/water p.c. the greater the
  rate of transfer across the membrane
• polarity of a drug, by increasing
  ionization will the lipid/ water p.c.
• polarity of a drug, suppression of
  ionization will the lipid/ water p.c.

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Routes of Drug Administration

• The route of administration (ROA) that is chosen
  may have a profound effect upon the speed and
  efficiency with which the drug acts

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• The possible routes of drug entry into the body
  may be divided into two classes
• Enteral
• Parenteral

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Enteral Routes

• Enteral - drug placed directly in the GI tract
• sublingual - placed under the tongue
• oral - swallowing (p.o., per os)
• rectum - Absorption through the rectum

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Sublingual/Buccal

• Some drugs are taken as smaller tablets which are
  held in the mouth or under the tongue.
• Advantages
• rapid absorption
• drug stability
• avoid first-pass effect

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Sublingual/Buccal

• Disadvantages
• inconvenient
• small doses
• unpleasant taste of some drugs

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Oral

• Advantages
• Convenient - can be self- administered, pain
  free, easy to take
• Absorption - takes place along the whole length
  of the GI tract
• Cheap - compared to most other parenteral routes

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Oral

• Disadvantages
• Sometimes inefficient - only part of the drug may
  be absorbed
• First-pass effect - drugs absorbed orally are
  initially transported to the liver via the portal
  vein
• irritation to gastric mucosa - nausea and vomiting

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Oral

• Disadvantages cont.
• destruction of drugs by gastric acid and
  digestive juices
• effect too slow for emergencies
• unpleasant taste of some drugs
• unable to use in unconscious patient

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First-pass Effect

• The first-pass effect is the term used for the
  hepatic metabolism of a pharmacological agent
  when it is absorbed from the gut and delivered to
  the liver via the portal circulation. The
  greater the first-pass effect, the less the agent
  will reach the systemic circulation when the
  agent is administered orally

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First-pass Effect cont.
Magnitude of first pass hepatic effect
Extraction ratio (ER) ER CL liver / Q where Q
is hepatic blood flow (usually about 90 L per
hour. Systemic drug bioavailability (F) may be
determined from the extent of absorption (f) and
the extraction ratio (ER)
F f x (1 -ER)
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First-pass Effect
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Rectal
1. unconscious patients and children 2. if
patient is nauseous or vomiting 3. easy to
terminate exposure 4. absorption may be variable
5. good for drugs affecting the bowel such
as laxatives 6. irritating drugs contraindicated
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Parenteral Routes

• Intravascular (IV, IA)- placing a drug directly
  into the blood stream
• Intramuscular (IM) - drug injected into skeletal
  muscle
• Subcutaneous - Absorption of drugs from the
  subcutaneous tissues
• Inhalation - Absorption through the lungs

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Intravascular
Absorption phase is bypassed (100
bioavailability) 1.precise, accurate and almost
immediate onset of action, 2. large quantities
can be given, fairly pain free 3. greater risk
of adverse effects a. high concentration
attained rapidly b. risk of embolism
c. OOPS factor or !_at_
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Intramuscular
1. very rapid absorption of drugs in aqueous
solution 2.repository and slow release
preparations 3.pain at injection sites for
certain drugs
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Subcutaneous
1. slow and constant absorption 2. absorption is
limited by blood flow, affected if
circulatory problems exist 3. concurrent
administration of vasoconstrictor
will slow absorption
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Inhalation
1.gaseous and volatile agents and aerosols
2.rapid onset of action due to rapid access to
circulation a.large surface area
b.thin membranes separates alveoli from
circulation c.high blood
flow Particles larger than 20 micron and the
particles impact in the mouth and throat. Smaller
than 0.5 micron and they aren't retained.
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Inhalation cont.

• Respiratory system. Except for IN, risk hypoxia.
• Intranasal (snorting) Snuff, cocaine may be
  partly oral via post-nasal dripping. Fairly fast
  to brain, local damage to septum. Some of the
  volatile gases also appear to cross nasal
  membranes.
• Smoke (Solids in air suspension, vapors) absorbed
  across lung alveoli Nicotine, opium, THC,
  freebase and crack cocaine, crystal
  meth.Particles or vapors dissolve in lung fluids,
  then diffuse. Longer action than volatile gases.
  Tissue damage from particles, tars, CO.
• Volatile gases Some anaesthetics (nitrous oxide,
  ether) precise control, petroleum distillates.
  Diffusion and exhalation (alcohol).
• Lung-based transfer may get drug to brain in as
  little as five seconds.

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Topical

• Mucosal membranes (eye drops, antiseptic,
  sunscreen, callous removal, nasal, etc.)
• Skin
• a. Dermal - rubbing in of oil or ointment
  (local action)
• b. Transdermal - absorption of drug through
  skin (systemic action)
• i. stable blood levels
• ii. no first pass metabolism
• iii. drug must be potent or patch
  becomes to large

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Route for administration -Time until effect-

• intravenous 30-60 seconds
• intraosseous 30-60 seconds
• endotracheal 2-3 minutes
• inhalation 2-3 minutes
• sublingual 3-5 minutes
• intramuscular 10-20 minutes
• subcutaneous 15-30 minutes
• rectal 5-30 minutes
• ingestion 30-90 minutes
• transdermal (topical) variable (minutes to hours)

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Time-release preparations

• Oral - controlled-release, timed-release,
  sustained-release
• designed to produce slow,uniform absorption for 8
  hours or longer
• better compliance, maintain effect over night,
  eliminate extreme peaks and troughs

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Time-release preparations

• Depot or reservoir preparations - parental
  administration (except IV), may be prolonged by
  using insoluble salts or suspensions in
  non-aqueous vehicles.

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Distribution

• Blood flow to tissues
• Exiting the vascular system once it has been
  delivered pass through pores in capillary wall

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Protein - binding

• Drugs can bind with proteins
• Parts of drugs will be bound during any given
  time period
• Impedes drugs ability to reach sites of action,
  metabolism, or excretion

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Metabolism

• LIVER
• Enzymatic alteration of drug structure

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Consequences of metabolism

• Accelerated renal excretion kidney cannot
  excrete highly lipid soluable
• Drug inactivation
• Increased therapeutic action
• Activation of prodrugs
• Increased or decreased toxicity

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Considerations in Metabolism

• Age
• Induction of drug metabolizing enzymes
• First-pass effect Nitroglycerin
• Nutritional status
• Competition between drugs

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Excretion

• KIDNEY
• Glomerular filtration blood to tubular urine
• Tubular reabsorption
• Active tubular secretion pumps for organic
  acids and organic bases to urine

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Monitoring drug levels

• Plasma drug levels
• Therapeutic range

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Drug Half-life

• Time requires for the amount of drug in the body
  to decrease by 50
• Will determine dosing requirements
• Goal - plateau

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Dosing

• Loading doses when plateau must be achieved
  quickly
• Routine smaller doses maintenance doses

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• Peak and trough levels

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• Maximal efficacy largest effect a drug can
  produce
• Potency one that produces its effects at lower
  dosages

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Receptors

• Drugs bind to receptors to produce effects
• Reversible

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• All that drugs can do is mimic the physiological
  activity of the bodys own molecules
• Block the physiological activity of the bodys
  own molecules

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Agonists

• Mimic the bodys own regulatory molecules

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Antagonists

• Drugs that block the actions of endogenous
  regulators

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Partial agonists

• Mimic the actions but with reduced intensity

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Drug Interactions

• Can have varying effects
• Direct chemical or physical IV preparation

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Drug Food Interactions

• Frequently decreased rate of absorption
• Grapefruit juice can inhibit metabolism
• with food with or shortly after meal
• empty stomach one hour prior to meal or two
  hours after

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Adverse drug reactions

• Side effect
• Toxicity
• Allergic reaction
• Idiosyncratic effect
• Iatrogenic disease
• Physical dependence
• Carcinogenic effect

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• Teratogenic effect induce birth defect
• Ways to minimize

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Variation in drug responses

• Age
• Body composition
• Gender
• Pathophysiology
• Tolerance
• Placebo effect
• Genetics
• Variability in absorption bioavailability
  oral ability to reach circulation
• Compliance

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• What does the term adverse reaction refer to?
• A. A life-threatening response to a response to
  a drug
• B. A drug-induced allergy
• C. A harmful, undesirable response to a drug
• D. An unpredictable response to a drug

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• What is an idiosyncratic response?
• A. a toxic reaction
• B. an allergic reaction
• C. a reaction peculiar to the patient
• D. an anaphylactic reaction

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• Which statement accurately characterizes
  geriatric patients compliance with prescribed
  drug regimens?
• A. compliance decreases with age
• B. compliance increases with age
• C. compliance increases with multiple health
  problems
• D. compliance decreases when more than three
  drugs are prescribed

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• END