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

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