Pharmacokinetics Absorption 2

Pharmacokinetics

Pharmacokinetics

study of drug movement in the body

ADME

• absorption

• distribution

• metabolism

• excretion

  • what the body does to drugs

What is Absorption

• movement of drug from site into blood

Rate of absorption

determines how quickly drugs effects occur

amount of drug absorption

determines how intense effect of drug will be

Factors affecting absorption

• rate of dissolution

• surface area

• blood flow

• lipid solubility

• pH partitioning

• activity of drug transport proteins

rate of dissolution

• means dissolving in solution

• must dissolve before absorption

fast rate of dissolution vs slow

fast = quick onset of action

slow = slow onset

surface area

• major determinant of absorption

• large surface area = fast drug absorption

Small intestine surface area

• small intestine = faster

• have villi making area larger

stomach surface area

• stomach = slower

• has rugae (folds) making small

blood flow

• drug absorption fastest in areas of high blood flow

• areas of high maintain concentration gradient

  • driving absorption

What increases blood flow

• exercise increased = increased drug absorption

what decreased blood flow

• heart failure

• severe hypotension

• hypothermia

• circulatory shock

lipid solubility

• lipophilic drugs absorb faster than hydrophilic drugs

• lipophilic drugs cross cell membrane

pH partitioning

• absorption is greater when there difference of pH

• drug becomes ionized in diff pH of blood & unable to cross out

• increased absorption & has concentration gradient

activity of drug transport proteins

• rate & extent of absorption can be impacted

• help enter & or exit cells

Uptake drug transports

• increased absorption

efflux drug transporter

• decreased absorption

enteral route of administration

• route of admin that involves GI

• pill

parental route of administration

• route of admin that doesn’t involve GI

• IVs

Other routes of administration

• sublingual

• transdermal

• pulmonary

• considered paternal bc no GI

Oral Admin Advantages

• safe

• convient

• economical

Oral Admin disadvantages

• incomplete

• variable absorption

Oral Drug Absorption in Intestine

• absorption is greatest in intestine

• bc large surface area

Oral admin & pH in intestine

• drugs that are weak acids are more efficient in small intestine bc its ionized

• rate is best in intestine vs stomach

Oral admin & pH in stomach

• acidic drugs should be absorbed in acidic stomach environment

• but size & thick mucous slows the rate

Pharmaceutical Phase

• occurs after tablet is swallowed

• involves disintegrates & dissolution

Without disintegration or dissolution

absorption is reduced

gastric emptying

• movement of stomach content into intestine

• increased gastric emptying = increase rate of absorption

increased gastric empyting (fast)

• taking medication on empty stomach

• taking medication w cold water

• laying on right side

• high osmolarity feeding (tube feeding)

• taking prokinetic drug (increase GI motility)

decreased gastric emptying (slow)

• high fat meals

• heavy exercise

• laying on left side

• anticholingeric drug - inhibits vagus nerve

enteric coating

• coating precent dissolution in acidic environment (stomach)

• dissolves in alkaline environment

when are centric coating drugs useful

for drugs that are destroyed by acidity

Bioavailability

• how much of a drug that enters blood stream when introduced into body & made available for use

Bioavailability Influced by

• drug formulation

• route of administration

• degree of metabolism

drug formulation - aqueous solutions & syrups

• highest

• no disintegration or dissolution phase

drug formulation - suspension

• particles suspended in liquid not in solution

• no disintegration phase

drug formulation - chewing tablets

• skips disintegration phase

• helps w dissolution

drug formulation - granules, capsules & compressed tablets

• must disintegrate & dissolve

drug formulation - enteric coated & timed release

• slowest

Sublingual

• placed under tounge

• venous drainage from oral mucosa goes into superior vena cava & takes to heart

• avoids metabolism thru liver

Sublingual Requirements

• must be lipophilic

• must be unchraged

• good for heart drugs

Transdermal preparations

• patches, ointments, sprays or lotions

• constant plasma drug level

• minimal peaks & troughs

Transdermal Disadvanatage

• tolerance may develop

• patches removed 6-10 hours to avoid

Factors Affecting Transdermal Absorption - thickness of skin

• thick skin is harder for medicine to pass

Factors Affecting Transdermal Absorption - hydration

• absorption increased when well hydrated

Factors Affecting Transdermal Absorption - hair follicles

• provide route to bypass epidermis

• more follicles = greater transdermal absorption

Factors Affecting Transdermal Absorption - area

• greater application area = greater absorption

Factors Affecting Transdermal Absorption - skin integrity

• psoriasis, burned skin, abraded skin = absorption increased

• skin barrier is compromised

rectal drugs

• useful for unconscious or vomiting pt

• 50% of rectal drugs bypass liver

Rectal adminstation

• suppository dissvolces & crosses rectal mucosa into blood

rectal disadvantages

• incomplete absorborption

• may irritate rectal mucosa

intravenous drugs

• directly into peripheral veins

Commonly used veins IV

• back of hand

• media cubiatal vein (elbow)

  • any visible vein works

IV - bolus

• single dose over short time

IV - drip

• continuous infusion over long time

• usually diluted in “vehicle” (saline)

IV advantages

• no absorption - bioavalibity is 100%

• allows precise control dosage & duration

• allows poorly soluble drugs that need dilution

• allows irritants to be injected slowly & diluted in blood

IV disadvantages

• expensive, invasive & inconvienet

• cannot be removed

• risk of injection, wrong formula, fluid overload

Subcutaneous

• in SubQ tissue

• only barrier is capillary wall

SubQ disadvantages

• irritants can’t be injected

• painful or tissue sloughing

SubQ - what determines rate of absorption

• blood flow & water solubility

• must water soluble to dissolve into extracellular fluid

Intramuscular

• determinants of absorption - blood flow & water solubility

• absorption determined by ability of drug to pass thru fenstraitons in cap wall

IM - advantages

• can be used for poor soluble drugs

• use to administer depot preparations

  • drug absorbed slowly over time

IM - disadvanatages

• pain / discomfort

• cause local tissue / nerve damage if improper

Factors Impacting IM absorption

• blood flow for each muscle

• Deltoid > Vastus lateralis > Gluteal

IM what increases & decreased blood flow

• exercise increased flow & increase absorption of drug

• decreased by heart failures, hypotension & hypothermia

Pulmonary - gaseous/volatile druges

• inhaled & absorbed into blood thru pulmonary epithelium

• vv fast absorption bc surface area of lung

• good for pulmonary diseases (asthma)