Pharmacology
Ideal Drug
EffectivenessSafetySelectivityReversiblePredictabilityEase of administrationFreedom from drug interactions
Ideal Drug
Low costChemical StabilityPossession of a simple generic name
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
Intensity of Drug responses
Administration – dosage and routePharmacokinetics PharmacodynamicsIndividual variation
Nursing Responsibilities
Last line of defense against errors!!!!!!!!!
Patient education
Utilize the nursing process
Drug Legislation
1906 – drugs should be free of adulterants1938 – testing for toxicity1962 – proof of effectiveness1970 – Controlled Substance Act –
Scheduled drugs1997 – Food and Drug Administration
Modernization Act
New Drug Development
Preclinical testing – prior to testing on humans
Clinical testingI – normal volunteers – except maybe
patients who have diseaseII and III – patientsIV – released for general use
Be neither the first to adopt the new nor the last to abandon the old!
Drug Names
ChemicalGeneric NameTrade Name
OTC drugs
Pharmacokinetics
Drug movement throughout the bodyAbsorption – movement of drug from its site of
administration into bloodDissolve – must dissolve before being absorbedSurface area – the larger the fasterBlood flow – most rapid where blood flow is
highLipid solubility - the higher the fasterpH partitioning
Absorption - Routes
IV – no barriers to absorption Intramuscular – good for poorly soluble drugs,
“time released”Subcutaneous – again no significant barriersOral – must pass through cells of epithelium,
enteric coatingSafer but highly variable absorption – enteric,
sustained-release, tablets
Routes of Drug AdministrationRoutes of Drug Administration
Robert L. Copeland, Ph.D.
Department of Pharmacology
www.med.howard.edu/pharmacology
202.806.6311
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
Drug AbsorptionFactors 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
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
Drug AbsorptionMechanisms of solute transport
across membranes– passive diffusion– filtration and bulk flow– endocytosis– ion-pairing – active transport
– Drug Absorption animation
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
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)
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)
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.
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
ImportantImportantInfoInfo
The possible routes of drug entry into the body may be divided into two classes:
–Enteral
–Parenteral
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
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
Sublingual/Buccal
Disadvantages– inconvenient– small doses– unpleasant taste of some drugs
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
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
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
First-pass EffectThe 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
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)
First-pass Effect
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 laxatives6. irritating drugs contraindicated
Rectal
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
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 !@#$%
Intramuscular
1. very rapid absorption of drugs in aqueous solution 2.repository and slow release preparations 3.pain at injection sites for certain drugs
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
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 flowParticles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained.
Inhalation
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.
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
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)
Route for administration -Time until effect-
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
Time-release preparations
Depot or reservoir preparations - parental administration (except IV), may be prolonged by using insoluble salts or suspensions in non-aqueous vehicles.
Distribution
Blood flow to tissuesExiting the vascular system once it has
been delivered – pass through pores in capillary wall
Protein - binding
Drugs can bind with proteins Parts of drugs will be bound during any
given time periodImpedes drug’s ability to reach sites of
action, metabolism, or excretion
Metabolism
LIVEREnzymatic alteration of drug structure
Consequences of metabolism
Accelerated renal excretion – kidney cannot excrete highly lipid soluable
Drug inactivationIncreased therapeutic actionActivation of prodrugsIncreased or decreased toxicity
Considerations in Metabolism
AgeInduction of drug metabolizing enzymesFirst-pass effect – NitroglycerinNutritional statusCompetition between drugs
Excretion
KIDNEYGlomerular filtration – blood to tubular
urineTubular reabsorption Active tubular secretion – pumps for
organic acids and organic bases – to urine
Monitoring drug levels
Plasma drug levels
Therapeutic range
Drug Half-life
Time requires for the amount of drug in the body to decrease by 50%
Will determine dosing requirementsGoal - plateau
Dosing
Loading doses – when plateau must be achieved quickly
Routine smaller doses – maintenance doses
Peak and trough levels
Maximal efficacy – largest effect a drug can produce
Potency – one that produces its effects at lower dosages
Receptors
Drugs bind to receptors to produce effects
Reversible
All that drugs can do is mimic the physiological activity of the body’s own molecules
Block the physiological activity of the body’s own molecules
Agonists
Mimic the body’s own regulatory molecules
Antagonists
Drugs that block the actions of endogenous regulators
Partial agonists
Mimic the actions but with reduced intensity
Drug Interactions
Can have varying effects
Direct chemical or physical – IV preparation
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
Adverse drug reactions
Side effectToxicityAllergic reactionIdiosyncratic effectIatrogenic diseasePhysical dependenceCarcinogenic effect
Teratogenic effect – induce birth defect
Ways to minimize
Variation in drug responses
Age Body compositionGenderPathophysiologyTolerancePlacebo effectGeneticsVariability in absorption – bioavailability – oral –
ability to reach circulationCompliance
What does the term adverse reaction refer to?
A. A life-threatening response to a response to a drug
B. A drug-induced allergyC. A harmful, undesirable response to a
drugD. An unpredictable response to a drug
What is an idiosyncratic response?A. a toxic reactionB. an allergic reactionC. a reaction peculiar to the patientD. an anaphylactic reaction
Which statement accurately characterizes geriatric patients’ compliance with prescribed drug regimens?
A. compliance decreases with ageB. compliance increases with ageC. compliance increases with multiple health
problemsD. compliance decreases when more than three
drugs are prescribed
END
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