Pharmacokinetics

the study of drug movement through the body. The effect of the body on the
drug.
Absorption the movement of a drug from its administration site into the circulation
Rate of Absorption how soon the effects of a drug will begin
Amount of Absorption intensity of the drugs effects
Factors affecting
absorption
rate of dissolution, surface area, blood flow, lipid solubility, pH partitioning,
Rate of dissolution
drugs in formulations that have rapid dissolution have a faster onset than
drugs with slower rate of dissolution
Surface Area
the larger the surface area the faster the absorption. Small intestine has
fastest absorption of oral administered drugs
Blood Flow
the more vascular a site the quicker the absorption. Works on concentration
gradient, blood containing newly absorbed drug will be replaced rapidly by
drug free blood.
Lipid Solubility Highly lipid soluble drugs absorb more rapidly.
pH partitioning
drug absorption and elimination ca be affected by acid/base concepts. Also
works on concentration gradient. Acid drugs are drawn toward alkaline and
vice versa. Important in treatment of overdoses.
Routes of administration enteral and parenteral and less commonly topical etc.
Enteral Administration via the gastrointestinal tract
Parenteral Administration drugs given by penetration of the skin and entry into the underlying tissue
IV
rapid effect maximal degree of control over circulating drug. Usually aqueous.
Not reversible.
Drawbacks of IV Infection, repeat dosage requires patent iv line.
IM
May be used for drugs that are aqueous and non-aqueous. Deltoid and
Vastus lateralis quicker than dorso-gluteal or ventro-gluteal admin. Related to
blood flow to tissue
Subcutaneous
Dependent on blood flow to the tissue. Slow and constant absorption, non-
irritating requires absorption into capillaries.
Oral
most common. Variable in terms of availability. Efficacy may be limited by
metabolism. Food in system may affect efficacy/action or delay gastric
emptying leading to destruction of drugs.
Distribution
The movement of drugs throughout the body. Dependent upon blood flow to
tissues, the availability of the drug to exit the vascular system and to a lesser
extent, the ability of the drug to enter the cells.
Speed of Blood flow
Well perfused organs such as brain, heart, kidney and liver receive most of
the drug in the first few minutes. Muscle, most viscera, skin and fat are slower
to receive drug, from minutes to hours.
Diffusion into Interstitial
Compartments
rapid diffusion occurs in most areas because of permeable capillaries. E.g..
Liver capillaries have much of basement membrane exposed by slit junctions
which enables rapid diffusion including large plasma proteins.
Blood brain Barrier
no slit junctions in brain so drugs must either pass directly through (lipid
soluble) or via active transport.
Biotransformation
Drug metabolism. The most important consequence of metabolism is
promotion of renal excretion.
Most important factor in
biotransformation
Renal excretion
Factors affecting
biotransformation
Induction, first pass effect, extremes of age, nutritional status, competition
among drugs.


Induction
Some drugs, acting on the liver, can increase the rate of their own or another
drug's metabolism. E.G.. Phenobarbital the classic enzyme inducer
First Pass rapid inactivation of oral drugs due to liver metabolism.
Metabolism relating to
lipophilic drugs
Lipophilic properties that promote a drug's passage through biologic
membranes and subsequent access to their sites of action also hinders
elimination of the drug.
Usual biotransformation of
drugs
usually biotransformed into more polar, inactive metabolites that are easily
excreted by body.
Hepatic Metabolism
Metabolites with increased biologic activity or even toxic properties may be
created through metabolism E.G.: Tylenol has a hepatotoxic metabolite.
Hepatotoxic definition
chemical-driven liver damage. It is a possible side-effect of certain
medications
Excretion Renal, billiary, fecal, breast milk, lungs, saliva, sweat
Renal Excretion
glomerular filtration, proximal tubule secretion, distal tubular secretion, renal
excretion
Plasma Drug Levels
there is a direct relationship between therapeutic and toxic responses and the
amount of drug present in plasma
MEC Minimum effective concentration
MEC definition the plasma drug level below which therapeutic effects will not occur
Toxic Concentration the plasma drug level at which toxic effects occur
Therapeutic Window
the range of plama drug levels falling between the MEC and the toxic
concentration. Drugs with narrow range of therapeutic window are more apt to
cause toxicity. Digoxin is the classic example
Drug Half life
the time required for the amount of drug in the body to decrease(eliminated)
by 50%. Drugs with a short half-life but a long dosing interval will lose the
MEC
Plateau
when the amount of drug eliminated between doses equals the dose
administered. Average drug levels will remain constant and plateau will have
been reached.
Techniques for reducing
fluctuations in plasma
drug levels
Continuous infusion (plasma levels kept constant), constant daily dose reduce
size and interval of dosage.
Loading Dose Large initial dose which achieve plateau rapidly
Maintenance Dose small doses to maintain plateau
Pharmacodynamics
the study of the biochemical and physiologic effects of drugs and the
molecular mechanisms by which those effects are produced. In short, what
the drug does to the body.
Dose Response
Relationship
Graded relationships. As the dosage increases the response becomes greater
Maximal Efficacy the largest effect a drug can produce
Potency the amount of drug that must be given to elicit a response
Drug Receptor
any functional macromolecule in a cell to which a drug binds to produce its
effect
Receptor Compatibility
the ability of a drug to bind to it's receptor depends on the size and shape of
the drug and its receptor, a single receptor can be responsible for regulating
several physiologic activities. Drugs mimic or block the actions of the body's
own regulatory mechanisms.
Intrinsic Activity
the ability of a drug to activate a receptor following binding and is linked to
efficacy.


Agonist drugs that bind with and activate receptors.
Antagonists drugs with affinity for receptors but no intrinsic activity
Tachyphylaxis
reduction in responsiveness brought on by repeated doses in short period of
time. Rapid tolerance. The MEC is elevated can occur from days to weeks of
administration. Metabolic tolerance is caused by the effects of the enzyme
induction on drugs. Accelerated metabolism can occur after days or weeks.
Additive Effect
2 drugs with similar properties are taken together.1+1=2 E.G. aspirin and
codeine boost analgesic properties if taken together
Synergistic Effect
The response of two drugs taken together is greater than the response of the
same drugs taken alone. 1+1=3 E.G. lasix and beta-blockers. Lasix removes
fluid and b-blockers block vasoconstriction causing a sharp decrease in bp
Antagonism
One drug inhibits the effect of another. 1+1=0 Vitimin K given to inhibit
bleeding from warfarin or Nalazone to antagonize morphine induced
respiratory depression
Lipophillic Drug
Metabolism
Lipophilic properties that promote a drug's passage through biologic
membranes and subsequent access to their sites of action also hinders
elimination of the drug.
Penicillin Types
Many Variations Penicillin G: IV or IV only aqueous preparations may be
given IV, Penicllin V only Oral.
Penicillin Action
Bactericidal: inhibits synthesis of cell wall, indicated in infections caused by
susceptible organizms, treatment for respiratory, genitourinary and
gastrointestinal infections
Antibiotic Commonalities All antibiotics have potential for renal toxicity, diarrhea and hypersensitivity
Bacteriostatic Inhibits growth but does not kill
Penicillin
Contraindications
hypersensitivity, drug interactions, can decrease effectiveness of oral
contraceptives
Penicillin: Nursing
Implications
Hypersensitivity reactions: risk for injury, Renal impairment: risk for,
Knowledge deficit: home care administration
Penicillin Patient Teaching
Do not take any penicillin or derivative (cephalosporin) if allergic, complete full
course of drug for greater effectiveness, follow dosing instructions very
carefully. Take most PCN on empty stomach, take each dose w/ full glass of
water, shake liquids well, report s&s of allergic reactions immediately and do
not take w/ fruit juices.
Peak and Trough Values Determine dose and time drug is to be given based on therapeutic levels
Cultures
Usually taken 30 mins after dose and then 30 mins before next scheduled
dose. Help to determine dosage. Temp at which to take cultures varies from
facility to facility
Antibiotics-Renal Toxicity
If BUN and creatinine levels are outside of normal range then the kidney
ability to excrete wastes may be impaired.
(Lanoxin)Digoxin
Classification/Action
Cardiac glycoside. Digitalis is naturally occuring. Increases the force of
contractions and decreases hr. Increases CO and blood flow to kidneys and
promotes diuresis.
Ionotroph force of contraction
Chronotroph heart rate
Lanoxin indications Heart failure, atrial arrhythmias,
Lanoxin Administration Oral or IV
Lanoxin Toxicity
rapid loading or digitalization (in order to reach plateau), impaired renal
function, age extremes, electrolyte imbalance especially hypokalemia and
also hypomagnesemia and hypercalemia
Lanoxin S&S of toxicity nausea, diarrhea vomiting, visual changes (colored halo), arrhythmias.
Lanoxin related labs digoxin level, BUN, creatinine, electrolytes.


Digoxin Toxicity therapeutic range 0.8-2.0 ng/ml.
Digoxin Antagonist Digibind. Digoxin immune fab.
Digoxin Patient Teaching
Pulse, consult health care provider before taking any other meds, avoid taking
missed dose, therapeutic effect is decreased with antacids.
Captopril/Capoten
Classification
Antihypertensive/ACE inhibitor
Captopril/Capoten Action
reduces the levels of angiotensin II thereby dilating blood vessels and
lowering bp
Captopril/Capoten
Indication
For mild to severe hypertension. More effective in young caucasians than in
young African Americans (fare better with combo therapy of diruetics and ace
inhibitors).
Captopril Side Effects
dry hacking cough (sensitivity in cough center), first dose syncope (bp
decreases and fainting after 1st dose or rapid increase in dose), hyperkalemia
Captopril Toxic Effects
Angioedema- swelling of mucosa and submucosa in face, lips, tongue and
potentially hands.
Captopril Nursing
Implications
Administer 1 hr before meals, monitor bp for first dose syncope, intruct pt to
lie down after first dose or after rapid increase in dose, adequate hydration,
monitor K levels.
Metoprolol (Lopressor)
classification
Beta-Adrenergic blocker. Prevents B-adrenergic receptors from responding to
sympathetic nerve impulses. Meta analyst may prevent MI
Metoprolol (Lopressor)
Action
Decreses hr, decreases force of contraction, cardiac output, conduction and
bp. May cause bronchoconstriction and may decrease glucose metabolism
Metoprolol Indications Angina, hypertension, arrhythmias, MI
Metoprolol Side Effects
hypoglycemia, severe bradycardia, airway resistance/pulmonary edema,
headache, flush dizziness, severe bradycardia, bronchoconstriction, nausea,
vomiting diarrhea
CMP Complete metabolic profile. Blood glucose, BUN, creatinine, lytes.
Metoprolol Nursing
Implications
Monitor hr/bp and report significant changes. Instruct pt to report dizziness,
fainting, edema, respiratory problems. Take before meals. Diabetic pt can
expect insulin changes, Abrupt withdrawal can lead to rebound sympathetic
overactivity (rebound htn), monitor labs cbc, cmp.
Furosemide (Lasix)
Classification
Loop diuretic
Furosemide (lasix) Action reduces the body's total water and salt by increasing urinary secretion
Lasix Indications Fluid volume excess
Lasix Contraindications electrolyte depletion, allergy (sulfonamide)
Lasix Side Effects
Ototoxicity (ringing), hypokalemia, hypotension, photosensitivity, diarrhea,
muscle spasms
Lasix Nursing Implications
Monitor I&O, weight and vitals. Teach pt to report s&s of ototoxicity. Monitor
cmp. Sunscreen.
Nitroglycerine
Classification
Organic Nitrate, Oral (Iserdil), IV, sublingual, transdermal
Nitroglycerine action
Acts directly on smooth muscle to promote venous dilation, decreases venous
return, decreases oxygen demand by decreasing workload
NTG side effects headache, hypotension, tachycardia (rare), tolerance
NTG Nursing Implications
Observe for relief of acute chest pain, teaching regarding diet, weight, lifestyle
factors related to angina, teaching regarding compliance with drug therapy


Heparin Classification
anticoagulant. IV or sub q. First Pass drug. One and 1/2 to 2 times control is
usualy considered therapeutic
Heparin Action
disrupts production of fibrin thereby disrupting the coagulation cascade.
Inhibits formation of clots but does not bust old ones up. Immediate after IV
and w/in 20 minutes of sub-q
Heparin Indications
prevention of DVT, and pulmonary embolism in susceptible pt. Prevention of
clotting during cardiac surgery, dialysis.
Heparin Lab PTT
Heparin Antagonist protamine sulfate
Heparin Contraindications
bleeding, high risk for bleeding, vitamin k deficiency, severe hypertension,
advanced kidney or liver disease.
Warfarin Classification anticoagulant.
Warfarin Action
acts in liver to prevent synthesis of vitamin K dependent factors. Onset is 3-5
days after administration
Warfarin Antagonist Aqua-Mephyton (vitamin K)
Warfarin Indications long term prevention of thromboembolic disorders
Warfarin Contraindications
bleeding, high risk for bleeding, vitamin k deficiency, severe hypertension,
advanced kidney or liver disease.
Warfarin Labs
PT and INR (weekly for the first month) dose adjustment highly individual,
Range of 2:3 is acceptable
Enoxaparin (Lovenox) Low molecular weight heparin sq admin.
Lovenox Antagonist protamine sulfate
Lovenox Lab Does not require lab monitoring
Anticoagulants Nursing
Implications
Monitor I&O, monitor labs, monitor for bleeding, instruct pt to report bleeding
Phenytoin (dilantin)
Classification
Anticonvulsant or antiepileptic drug
Dilantin Action
Stabilization of neuronal membranes thereby limiting spread of seizure
activity.
Dilantin Indication Prophylaxis and Rx of grand mal seizures
Dilantin Administration
Oral or IV (can cause hypotension IV), Long half life. Not compatible with
anything in IV line only saline. Mixing causes chalky precipitate.
Dilantin Contraindications
Heart block, dilantin slows blood flow/ hr. May increase blood glucose caution
in diabetics, concurrent use of antacids may decrease efficacy.
Dilantin Nursing
Implications
Adverse effects (GI, CNS) most likely to occur in geriatric population
Dilantin Labs
Dilantin level, hepatic profile (highly metabolized in liver), cbc. Flush IV before
admin.
Dilantin Patient Teaching
proper dose, compliance with therapy, if dose is missed do not double up,
avoid abrupt discontinuation, avoid alcohol. Take immediately after meals.
Sodium Bicarbonate
Special Note
Not compatible with other drugs IV


Zofran (Ondansetron)
Classification
Antiemetic
Zofran Action blocks central serotonin receptors thus blocking the vomiting center.
Zofran Indications
Emetogenic cancer therapy as well as other causes of NV (used pre-op
and/or post-op)
Zofran Nursing Indications
Management of possible headache, management of constipation, report cv
symptoms
Zofran Side Effects constipation, headache common, cardiovascular changes
Insulin Classifications Parenteral antidiabetic agent/ hormone
Insulin Action
promotes the uptake of glucose by cells as well as other functions related to
carbohydrate metabolism
Insulin Types (examples)
regular (rapid onset short duration), Lispro (humalog) rapid shorter acting
analog of regular, Neutral Protamine Hagedorn (NPH) intermediate acting,
Ultralente: long acting, Glargine (Lantus) long acting
Insulin
100 units per ml. Regular only insulin given IV. Rotate sites, monitor blood
glucose levels.
Insulin Nursing
Implications
Most serious consequence of insulin therapy is overdose manifested by:
profuse diaphoresis, confusion, irritability, incoherent speech, hunger,
headache, palpitations, tachycardia, blurred vision, convulsions and coma
Insulin Patient Teaching
administration, diet, carry quick form of carbohydrate, Sx hypoglycemia,
identification
Albuterol (Ventolin)
Beta 2 Agonist, stimulates the Beta 2 receptors to relax smooth muscle in
bronchioles.
Albuterol Adverse tremors, tachycardia
Prednisone Classification Glucocorticoid
Prednisone Action Increases synthesis of glucose, suppresses immune response
Prednisone Indications RA, asthma
Prednisone Adverse
affects
Poor wound healing, hyperglycemia, electrolyte imbalances.
Prednisone Nursing
Implications
monitor for hyperglycemia