PHARMACEUTICAL PHASE – dissolves in GI tract.  Those with enteric coating dissolve in alkaline small intestine 

PHARMACOKINETIC PHASE – movement of drug, 4 components 

ABSORPTION – moved into body fluids in tissues.  Rate of absorption depends on how administered: IV quickest, oral slowest; fat soluble stay in body longer, more risk for toxicity.   

Water soluble peed out fairly quickly and less chance of toxicity 

Absorption is very individualized 

3 types of absorption and 1 consideration: 

ACTIVE TRANSPORT – uses cell energy to go from low to high concentrations 

PASSIVE TRANSPORT – no energy, high to low concentrations 

PINOCYTOSIS – cells engulf drug in vescicles to move 

FIRST PASS EFFECT – first use of drug may be met with greater detoxification by liver, so may need a larger dose or more frequent admin; affects absorption 

DISTRIBUTION – through circulation, reacts with receptors;  

depends on proteing binding 

when bound to proteing, loses therapeutic effects 

Only free drug produces effect 

Goes quickly to areas with lots of blood like heart, liver, kidneys 

Affected by SOLUBILITY – ability of drug to cross cell membrane; E.g. a lipid will easily pass through and water soluble doesn’t 

METABOLISM = BIOTRANFORMATION – drug changed to more or less active form for excretion; usually rendered inactive, though sometimes metabolites have activity; done in LIVER mostly, sometimes KIDNEYS, LUNGS, PLASMA, INTESTINAL MUCOSA 

EXCRETION – by kidneys usually, sometimes sweat, breast milk, breath or GI feces 

if there is kidney disease, may need smaller dose and close monitor 

Also children and elderly have less kidney fnx 

PHARMACODYNAMIC PHASE – drug actions, mechanisms, how work 

Most drugs have affinity for target sites, certain tissues 

Drugs do one of two things or both 

ALTERATION OF CELLULAR FUNCTIONING – most drugs do this, by 

RECEPTOR-MEDIATED DRUG ACTION – drug binds to a cell receptor as either an 

AGONIST – stimulates the cell, or 

ANTAGONIST – blocks receptor.  Are 2 kinds of antagonists: 

COMPETATIVE – competes with agoists 

NONCOMPETATIVE – binds receptor and blocks agoists 

RECEPTOR MEDIATED DRUG EFFECTS – depends on # of receptors – the mroereceptors, the greater the response 

ALTERATION IN CELLULAR ENVIRONMENT –  

physically , e.g. changes osmotic pressure (manitol for brain edema), sunscreen changes lubrication, activated charcoal changes absorption   

chemically; antacids change pH (a chemical change) 

ADVERSE DRUG REACTIONS – include side effects (common) in this book to serious and even fatal. 

ALLERGIC REACTION – an immediate HYPERSENSITIVITY raction – usually begins after more than one dose 

Immune sx responds as if ANTIGEN, forming ANTIBODIES 

Mild to life threatening 

Onset ranges from sedoncds to days – most immediate usually most severe 

ANAPHYLACTIC SHOCK – serious! 

Bronchospasms, dyspenea, wheezing, VERY LOW BP, rapid heart  beat, syncope, cardiac arrest 

Can use EPINEPHRINE for tx and can treat each symptom (like benedryl for itching)\ 

ANGIOEDEMA = ANDIONEUROTIC EDEMA – another rype of allergic drug rxn where fluid collects in subcut tissues – mostly eyelids, lips, nouth, throat – may block airway leading to ASPHYXIA 

DRUG IDIOSYNCRACY- very unusual rxn, or rxn opposite of expected therapeutic rxn – often from a genetic difference 

E.g. those with G6PD deficiency can’t tolerate aspirin and sulfanamides b/c RBS hemolysis (destruction); over 100,000 have this deficiency in US 

DRUG TOLERANCE -  sign of physical dependence 

CUMMLULATIVE DRUG EFFECT – esp those with livier/kidney disease leads to toxicity.  Must give lower dose or not at all. 

TOXIC REACTIONS – most drugs are toxic if too much are given or accumulate from pathology (above) 

Some drugs have narrow margin of safety like LITHIUM so must monitor closely 

e.g. STREPTOMYCIN toxicity can damage 8th cranial nerve leading to permanent hearing loss 

some toxic levels have antidotes like Digibind for digitalis 

seom toxicity from differing genetics