Block I - Kinetics - A-D Flashcards
Site of absorption: oral
Mouth -> stomach/SI; safe, economic, convenient; acidic best in stomach; basic best in SI
Site of absorption: sublingual
Under tongue -> cap network -> systemic circ; Diffuse rapidly, bypass GI environ
Site of absorption: IM
Aqeous: rapid; Depot: delayed release.
Site of absorption: IV
Rapid plasma concentration release. 100% bioavailable. Cannot be recalled.
Site of absorption: inhaled
Goes to brain quickly. Pt may have hard time controlling dose.
Site of absorption: transdermal
Lipophilic drugs absorbed best this way. Slow/sustained delivery. Rate of absorption can vary (based on underlying tissue composition). Bypasses liver first-pass.
Site of absorption: parenteral
Bypass enteric system (eg IV, IM subcut). Used to treat unconscious pt, when quick delivery is needed, drugs unstable in GI. High bioavailability; cannot be recalled.
Site of absorption: epidural
Administered via catheter (slow admin). Bypasses blood-brain barrier. Used for pain relief.
Site of absorption: intrathecal
Injected directly into subarachnoid space. Used when rapid CNS effects needed. One injection in contrast with epidural (continuous).
Site of absorption: rectal
Some of drug bypasses liver first pass. Ideal for comatose/vomiting pts. May be incomplete/erratic absorption.
Method for delaying absorption: delayed released preparations
Oral meds with special coating to extend time over which drug is released. Good for drugs with short half life.
Method for delaying absorption: depot preparations
IM injections with suspension of drug in non-aqueous solution. Slowly dissolves, sustained-release.
Method for delaying absorption: implanted pumps
Release drugs subQ; via pump (insulin) or solid (hormones).
Method for delaying absorption: transdermal patches
Sustained release of drug to achieve systemic effects. Absorption depends of location and lipid solubility of drug.
Method for delaying absorption: pH sustained preparations
Drugs manufactured to withstand very low pH in order to control rate of absorption to stay within therapeutic window
Method for delaying absorption: patient controlled administration (PCA)
Pts self-administer medication at a predetermined dose.
Bioavailability
Fraction of administered drug that reaches systemic circulation. Compare to plasma levels of drug when given IV.
Factors influencing bioavailability: 1st pass hepatic metabolism
Drug rapidly metabolized in liver during first pass, amt of drug to gain systemic circ access decreased.
Factors influencing bioavailability: solubility of drug
Very hydrophilic drugs poorly absorbed b/c can’t cross cell membrane. Very hydrophobic drugs poorly absorbed b/c can’t gain access to cell surface. Optimal: drug that is mostly hydrophobic but still some solubility in aqueous solutions.
Factors influencing bioavailability: chemical instability
Some drugs unstable in gastric pH.
Factors influencing bioavailability: nature of drug formulation
Factors that influence ease of dissolution and thus alter absorption; particle size, salt form, enteric coatings, etc.
Difference between plasma conc curve: IV/IM/oral
IV: high peak, IM: med peak, oral: low peak
Loading dose
Single dose of drug given to elevate plasma levels to steady state.
Changes in stomach pH and affect on absorption of acidic and basic drugs
Acidic drugs: like to be absorbed in stomach (pH 1-2). If pH lowered in stomach, acidic drugs like. If raised (with meal) then it don’t like. Basic drugs: like to be absorbed in SI (pH 3-6). If pH raised in stomach, may be absorbed there.
Proteins drugs bind
Albumin (acidic strong, basic weak), alpha 1 glycoprotein, tracer proteins; free drug (active)
How blood-brain barrier prevents drugs from entering brain
Tightly packed endothelial cells of capillaries require drugs to be small, nonpolar, and lipophilic to go thru active transporters from blood across BBB.
Volume of distribution
Volume of fluid that total amount of drug would have to occupy to have same concentration as blood plasma.
Physiologic volume vs volume of distribution
Physiologic volume = extracellular + intracellular fluid. If drug bound to tissue, then volume of distribution can be well over amount of plasma or total body water.
Small VoD
Stays in circulatory system. More acidic drugs, low lipid solubility, high plasma protein binding, low tissue binding.
Large VoD
Hightly tissue bound. Basic drugs (greater tissue binding than acidic), high lipid solubility, low plasma protein binding, high tissue binding.
