Guide
Terminology PharmacologyStudy Pharmacology study of the effect of chemical substances on living systems Pharmacotherapeutics effects of drugs in the human system for various disorders Pharmacodynamics experimental science pertaining to theories of drug action Pharmacokinetics study of drug's alterations as it is absorbed, distributed, bound to or localized in tissues, biotransformed and excreted Pharmacogenetics study of genetically-induced drug responses that are often responsible for some idiosyncratic responses Drugs FDA includes any substance listed in the USP or British pharmacopedia and all substances other than food or devices capable of altering body structure or function Basic function a drug can only facilitate normal cellular function, effect change by: 1. Stimulation or depression of target cell activity 2. Replacement of deficient subsystems 3. Killing or weakening foreign invading organisms 4. Irritation General properties: 1. Modify existing functions 2. Exert multiple actions rather than a single effect 3. Drug function is a result of a physiochemical interaction between the drug and a functionally important molecule in the body Methods used to determine potency: 1. Chemical assay - chemical analysis to determine ingredients and amount 2. Bioassay - determines amount of solution need to produce a desired effect on a lab animal under certain conditions Steps in drug development Preclinical testing (in animals) o Animal studies look for toxicity (acute toxicity is represented by the LD50 (dose that is lethal in 50% of lab animals tested)), therapeutic index (ratio of median lethal dose (LD50) to the median effective dose), how and where it's absorbed, how metabolized & excreted Investigational New Drug (IND) status Clinical testing (in humans) Phase I normal volunteers, tests for metabolism and biological effects Phase II patients, tests for therapeutic utility and dosage range Phase III patients, tests for safety and effectiveness Conditional approval of new drug application (NDA) Phase IV early: limited, closely monitored marketing, late: unlimited marketing with postmarking surveillance Drug Schedules Schedule I high potential for abuse, lack of accepted medical use (cocaine, heroin, LSD) Schedule II high potential for abuse and high potential for psychological and/or physical dependence, but have accepted medical use (morphine, demoral)
Schedule III less potential for abuse, moderate potential for dependence (aspirin combined with codeine, barbituates) Schedule IV low potential for abuse, limited potential for dependence (tranquilizers, chloral hydrate) Schedule V very low potential for abuse and low potential for dependence (cough syrup with codeine) FDA pregnancy categories A no risk to fetus B no risk to animal fetus C adverse effects recorded in animals D possible fetal risk in humans reported, considering potential benefit versus risk may warrant use in pregnant women in selected cases X positive evidence for abnormalities in humans, don't use Nurse's Role in Drug Therapy 1. Storage, preparation and administration 2. Promotion and observation for intended effect 3. Prevention, detection and minimization of side effects and interactions 4. Client education Three conditions must be met before nurse can administer medications 1. Order must be valid and up-to-date 2. Nurse must be licensed 3. Must know purpose, action, effect, dose, major side and toxic effects of drug, and teaching Nursing Process/Drug Therapy 1. Assessment 1.1. Taking a drug history (allergies, current meds and what they're taken for, meds that have been discontinued within last 6 months, OTC medications, alcohol and smoking, caffeine,) 1.2. Assess for intended effects 1.3. Assess for interactions 2. Nursing Diagnosis 3. Planning 4. Intervention 4.1. Promote intended effect 4.2. Assist patient to cope with side effects 4.3. Teaching 4.4. Storage, preparation, administration 5. Evaluation Type of Drug Orders PRN - only as necessary, use judgment Protocol - set of criteria that serves as a directive under which medication may be delivered Properties Influencing Pharmacokinetic Activity 1. Physiochemical properties of drugs 1.1. Ionized (polar) water-soluble, doesn't readily diffuse through cell membranes 1.2. Non-ionized (non-polar) lipid-soluble, more apt to cross cell membrane 2. Physiochemical properties of cell membranes 2.1. Passive transport - doesn't require energy Simple diffusion - higher to lower concentration until equality is achieved Facilitated diffusion (carrier-mediated) - drug combines with something in body to facilitate transport into cell
Filtration - similar to facilitated diffusion except from high to low hydrostatic pressure 2.2. Active transport Carriers - similar to facilitated diffusion but requires energy Absorption - movement of drug molecules from site of entry to circulating fluids Variables that affect drug absorption i. Nature of absorbing surface (faster through a single layer of cells than though multiple layers, better absorption with larger surfaces) ii. Blood flow to site of administration iii. Solubility of drug - drug must be in solution to be absorbed; the more soluble the drug, the more rapidly it will be absorbed iv. Influence of pH - when in solution, a drug that is acidic becomes relatively unionized in an acid environment (it can diffuse across the membrane in such an environment - like the stomach), basic drugs become ionized in acidic environments and are not readily absorbed v. Drug concentration - drugs that are administered in high concentrations are more readily absorbed than drugs given in low concentrations vi. Dosage form 1. Enteric coating - prevents drugs from being broken down by gastric solutions, to prevent dilution of drug before it reaches the small intestine, helps to prevent nausea and vomiting, to provide a delayed action of the drug Routes of Drug Administration - affects rate at which onset occurs and magnification of response 1. Enteral - any portion of GI tract 1.1. Oral (po) - safest, most convenient, economical, but unreliable and slowest route, first to portal system in liver before entering systemic circulation 1.2. Sublingual (SL) - enters systemic circulation without going through the liver (avoid destruction by GI fluids or liver) ex. nitroglycerin 1.3. buccal - placed between cheek and teeth, directly into systemic circulation 2. Rectal (PR) - unreliable, directly to systemic circulation 3. Vaginal - usually administered to combat bacterial or fungal infections 4. Parenteral 4.1. Subcutaneous (SC) - appropriate for drugs in small volumes where you want slow absorption and sustained effects (ex. insulin) 4.2. Intramuscular (IM) - more rapid absorption than SC, appropriate for a larger volume of the drug (3-5 cc) 4.3. Intravenous (IV) - injected directly into bloodstream to circumvent absorption process, drugs must be in solution, usually administered slowly 4.4. Intrathecal - injected directly into sub-arachnoid space, bypasses blood-brain barrier 5. Topical - rapid absorption, absorbed systemically 6. Nasal - usually given for astringent effect or to treat infection 7. Conjunctival - eye 8. Inhalation - given for pulmonary problems, usually given under pressure (nebulizer, etc.) 9. Ear drops Bioavailability - percentage of active substances in a drug that is absorbed and becomes available to tissue Biologically equivalent - attain similar concentrations in tissues at similar times, Therapeutically equivalent - provide equal effectiveness in clinical trials Distribution Drug reservoirs - drugs are stored and the levels stay high in the body for longer
1 Plasma protein binding - some drugs attach to proteins, primarily albumin (contained in blood), {free drug + protein = drug protein complex (pharmacologically inactive)}, more drug is released from the protein when it is metabolized Degree (%) of drug binding - the higher the %, the longer the drug stays in the body Competition for binding - albumin and other plasma proteins provide a number of binding sites, two drugs can compete for the same binding site and cause problems because too much of the drug may be free if it can't bind - don't give competing drugs at the same time or adjust dosage to make sure too much isn't free Hypoalbuminemia - too little albumin, too much of the drug is free, adjust dosage of drug or given albumin replacement 2 Tissue binding Fat tissue - lipid-soluble drugs have high affinity for adipose tissue, watch for cumulative effects Bone - some drugs have a high affinity for bone, accumulates by absorption into bone crystal lattices (ex. tetracycline), can interfere with growth of bones and can produce discoloration of teeth if they're growing in, contraindicated in pregnant women and young children Distribution barriers - specialized structures that are made of biological membranes that serve as barriers 1. Blood brain barrier (BBB) - distributes only lipid-soluble drugs, many antibiotics have trouble crossing it 2. Placental barrier - non-selective passage of drugs across placenta to fetus, tissue enzymes in the placenta can metabolize and inactivate some drugs, does not afford complete protection to fetus Biotransformation - chemically changes a drug by converting it to a more water soluble compound for excretion, some drugs don't become active until they're biotransformed Sites: liver (primary), plasma, kidneys, lungs, intestinal mucosa Consequences - promotes kidney excretion of drug, can cause drug inactivation, can increase or decrease toxicity Chemical alterations - produced by microsomal enzyme system (P450 system - refers to cytochrome P450 group of 12 related enzyme families which allow the body to metabolize potentially toxic compounds) (usually affect lipid-soluble non-polar drugs), break down drug to make them more water-soluble and easier to excrete Enzymes are relatively non-specific (can break down a wide variety of different compounds), liver has the capacity to synthesize more enzyme in response to exposure of a high concentration of certain drugs Hepatic First Pass Effect - initial biotransformation of drug (on passage through the liver from the portal vein) that produces a loss of pharmacologically active molecules Transformation purpose is to increase polarity and water solubility of drug molecules 1. Nonsynthetic reaction oxidation, hydrolysis, reduction 2. Conjugation or synthetic reaction union of polar group of drug with another substance more water soluble Metabolic Pathways for Drug Transformation 1. Serial transformation - undergoes several transformations one after another A B C 2. Parallel transformation - one product will result in three metabolites, A B, A C, A D Excretion - drugs and pharmacologically active or inactive metabolites are eliminated from body through: 1. Kidney (most important route) 1.1.Passive glomerular filtration 1.2.Active tubular secretion 1.3.Urinary pH (weak acids excreted more readily in alkaline urine), use sodium bicarbonate for acid poisoning, vitamin C for basic poisoning 2. Intestines - biliary excretion (metabolite can be secreted into bile from liver and then into duodenum) 3. Lungs - drugs are usually intact (not metabolized) 4. Sweat and saliva
5. Mammary glands - excreted in breast milk, breast milk is acidic so basic compounds such as narcotics will be excreted and given to child Pharmacodynamics - how the drugs exert their effects on target structures, one of the following interactions occurs: Drug-Receptor Interaction - key (drug) fits into lock (receptor), hypothesis: drugs are selectively-active substances that have a high affinity for a specific chemical group or particular constituent of a cell, active site of the drug selectively combines and interacts with some molecular structure within the cell to produce its effect, an agonist drug would stimulate the receptor, antagonist binds to a receptor and prevents the cell from responding, o Competitive antagonist - has an affinity for the same receptor site as an agonist, competition inhibits action of the agonist, increased concentration of the agonist will overcome the competitive antagonist o Non-competitive antagonist - will inhibit agonist response no matter the amount of agonist Drug-Enzyme Interaction - drug resembles an enzyme substrate, therefore combines with the enzyme altering or inhibiting a physiologic response Nonspecific drug interaction level Plasma profile graphically depicts relationship of serum drug level and time course through the body Narrow margin of safety narrow range between therapeutic dose and toxic dose Therapeutic range extends from minimal effective concentration to some point below the toxic level Factors affecting drug action 1. Age and weight (body mass) Elderly Increased gastric pH decreased absorption that are normally non-ionized at low pH Increased body fat decreased levels of fat-soluble drugs Decreased body water increased blood levels of water-soluble drugs Decreased serum albumin increased unbound drug increased drug activity Decreased cardiac output decreased drug metabolism and excretion Decreased renal blood flow decreased drug excretion Decreased splanchnic blood flow decreased absorption of drugs given orally, decreased metabolism, excretion, or both Decreased liver mass and hepatic blood flow decreased drug metabolism, esp. first pass Infants High total body water volume expanded distribution, diminished blood levels of water-soluble drugs Low body fat increased blood levels of lipid-soluble drugs Increased membrane permeability enhanced topical absorption, drugs can enter CNS rapidly Relative lack of gastric acid exaggerated absorption of drugs that are partially inactivated by gastric acid, or drugs that are normally ionized at low pH Immature body temperature regulation may dehydrate quickly, thereby elevating blood concentrations of drug Immature kidney or liver function delayed excretion or metabolism of certain drugs 2. Sex Women have more fat, so fat-soluble drugs are more widely dispersed 3. Genetic factors Allergies can be inherited G6PD abundant in tissues of most people and it plays a role in maintaining active hemoglobin in RBCs, some people lack adequate concentrations due to genetic variations doesn't normally cause a problem, but if exposed to certain chemicals the RBCs are destroyed sulfonimides, antimalarials, moth balls, fava beans
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Rate of drug acetylation half the population have a slow rate Psychological factors Illness and disease Altered drug excretion dose or frequency needs to be changed, related to kidney function and creatinine clearance Edema decreased concentration of water-soluble drugs (and possibly potency) Digitalis preparations narrow margin of safety, low K enhances the effect of it Liver disease decrease in drug metabolism and increase in drug levels, highly protein-bound drugs will have a higher free concentration GI disease mainly affects absorption, changes in pH can affect ionization Cardiovascular disease not enough perfusion will interfere with absorption and metabolism Increased fiber diet increases excretion Malnutrition low albumin and run the risk of overdose with highly protein-bound drugs Time of administration Environment Compliance
Iatrogenic Responses groups of adverse effects produced unintentionally by the MD in treatment of the client, five major syndromes: 1. Blood dyscrasias bone marrow depression 2. Hepatic toxicity hepatitis-like syndrome 3. Renal damage glomerular damage, many antibiotics cause renal damage 4. Teratogenic effects malformations of fetuses in first trimester 5. Dermatologic effects psoriasis, excema, acne Adverse Drug Responses Idiosyncracy any abnormal response to a drug that may manifest itself by: overresponse, underresponse, different effect, unpredictable and unexplainable symptoms Tolerance Cumulation body doesn't metabolize one dose before the next is administered Drug antagonism Summation (addition) combined effect of two drugs produces a result that equals the sum of the individual effects of each drug Synergism combined effect of drugs is greater than the sum of each individual agent if it was acting alone Potentiation concurrent administration of two drugs in which one drug increases the effect of the other Biologic half-life time required to reduce to one half that amount of unchanged drug that is in the body at the time equilibrium is established, rate of metabolism and excretion determines half-life, drugs with short half-lives have to be given more often, lengthened if person has hepatic or renal dysfunction Autonomic Nervous System maintains the internal environment of the body at an optimal level cardiac muscle, smooth muscle, glands 1. Sympathetic (fight or flight) a. Sight adrenal medulla secretes epinephrine & pupils dilate (alpha), ciliary muscles relax for far vision b. Need glucose for energy liver breaks down glycogen to glucose c. Need oxygen so glucose can be used for energy bronchi dilate d. Need to get glucose and oxygen to muscles and vital organs increased rate and force of contraction of heart, dilation of coronary and muscle vessels, rest of vessels constrict rise in BP e. Blood shuttled away from GI tract
i. Alpha 1 and 2 smooth muscle contracts, cause vasoconstriction and uterine contraction, alpha 2 causes cardiovascular depression and hypotension ii. B1 (cardiac musle) contracts more forcefully iii. B2 (bronchial, GI, urinary and ciliary muscles) respond by relaxing 2. Parasympathetic response a. Eye pupil constricts, ciliary muscles accommodate for near vision b. CV decrease in HR, dilation of coronary, cerebral, and visceral blood vessels c. Respiratory bronchi constrict d. GI smooth muscle constricts, increase in secretions, relaxed sphincters, gallbladder contracts, liver increases bile secretion, pancreas increases digestive enzyme secretion and insulin e. Urinary tract bladder contracts, urinary sphincter relaxes f. *SPLUDD* salivation, perspiration, lacrimation, urination, digestion, defecation Autonomic Drug Terminology 1. Same effects as SNS stimulation (thoracolumbar) a. Sympathomimetic b. Adrenergic stimulates either alpha, beta 1 or beta 2 receptors or all three) i. Epinephrine (adrenaline) 1. Effects: a. increases BP b. increases blood flow to skeletal muscles, heart, brain c. increases pulse with possibility of arrhythmias d. GI smooth muscle relaxation e. dilation of bronchial smooth muscle f. increased glucose, lactate, and fatty acids g. insulin secretion inhibition 2. Clinical indications a. acute bronchospasm, laryngeal edema, anaphylactic shock b. cardiac arrest 3. Adverse effect similar to stage fright ii. Norepinephrine (levophed) 1. Action potent alpha stimulant, constricts arterioles and increases peripheral resistance, slows heart rate 2. Side effects bradycardia, fatal arrhythmias, hypertension, headache, renal or hepatic failure, local tissue necrosis, tremors 3. Nursing implications monitor constantly while receiving drug (BP, pulse), q2 minutes until stable and then every 5 minutes, observe and record mental status, skin temperature and color, I & Os, patient complaints (headache, vomiting, palpitations, etc.) iii. Isoproterenol sulfate (Isuprel) 1. Action potent beta 1 and beta 2 stimulant, increases HR and force of contraction (beta 1) and decreases peripheral resistance and blood pressure, dilates bronchioles (beta 2) 2. Side effects CNS (headache, nervousness, anxiety, tremors), CV (tachycardia, ventricular arrhythmias, palpitations, precordial pain) c. Adrenergic agonists d. Beta or alpha agonists 2. Inhibits sympathetic stimulation a. Sympatholytic b. Antiadrenergic i. Alpha 1 receptor blockers decreases BP by decreasing ii. Example: Prazosin (used to treat hypertension)
iii. Side effects orthostatic hypertension, syncope/vertigo, weakness, palpitations/tachycardia, headache c. Alpha or beta blockers i. Beta blockers (adrenergic inhibitors) lowers BP by decreasing CO and release of rennin from kidneys, decreases cardiac contractility a. Cardiac-select affect beta 1, Atenolol b. Non cardiac-select affects beta 1 and beta 2, Propranolol 2. Side effects bradycardia, hypotension, fatigue, drowsiness, decrease in contractility, bronchoconstriction, insomnia, strange dreams, sexual dysfunction, impotence 3. Uses hypertension, angina, heart failure 4. Nursing implications a. Dose must be individualized b. Careful health history c. Monitor BP and pulse d. Monitor I&O, qd wt. e. Fasting more than 12 hours, may induce hypoglycemia f. Do not discontinue abruptly (may result in angina, heart attack, or fatal arrhythmia) g. If bradycardia occurs, administer atropine h. Effects of drug during pregnancy not established i. Dose decreased in presence of hepatic and renal disease d. Adrenergic antagonists 3. Same effects as PNS stimulation (craniosacral) a. Parasympathomimetic b. Cholinergic used primarily to treat conditions of GI and GU tract, glaucoma, monitor for urination if given after surgery c. Cholinergic agonists 4. Inhibits PSN stimulation a. Parasympatholytic b. Anticholinergic i. Prototype atropine sulfate ii. Effects used mostly for its CV effects 1. Slight decrease in HR with usual clinical doses, moderate-large doses cause increased HR, decreased respiratory tract secretions, antispasmodic effects, relaxation of ureters, smooth muscle of gallbladder, and bile ducts 2. Contraindicated in those with glaucoma increases IOP iii. Side effects can't see, pee, spit, shit c. Cholinergic blockers d. Cholinergic Classification: Blood Pressure = CO x PVR Once hypertension is confirmed, look for organ damage o CV heart failure o CNS TIA, stroke, aneurysm o Renal damage o Retinopathy Hypertension therapy (BP 140/90 or greater) o Begin lifestyle modifications o Drug therapy (uncomplicated HTN) Diuretics initial drug of choice for uncomplicated hypertension (particularly thiazides), lower BP by promoting urinary excretion of Na and water lower blood volume, blacks and the elderly are good candidates because of low plasma rennin and high intracellular Na
Beta-blockers blacks and elderly don't respond well to them because of low rennin, lower BP by reducing CO and the release of rennin from the kidneys, decreases heart rate, dilate blood vessels, more effective in whites and those with a history of an MI or angina, blacks and elderly don't respond well because of low rennin, mask signs of hypoglycemia, used with caution in those with heart problems and asthma Angiotensin-converting enzyme (ACE)) inhibitors decreases BP by blocking the enzyme that converts angiotensin I to angiotensin II (potent vasoconstrictor) veins are dilated and there is a decrease in the release in aldosterone), first line drugs in those with heart failure and diabetes because they preserve renal function, most effective in young white adults who tend to have mid-high levels of rennin and are insensitive to salt, inhibits aldosterone release can cause K retention Examples: Captopril (captoten) and Enalopril (vasotex) Adverse effects *cough, *hypotension, *hyperkalemia, rash, edema, loss of taste, proteinuria, neutropenia Angiotensin II receptor blockers prevents against angiotensin-II mediated vasoconstriction (PP) Ca channel blockers help to prevent vasospasm, stops movement of Ca into cells, relax smooth muscle which causes vasodilation, inhibits reabsorption of Na in renal tubules Example: Verapamil, Nifedipine Contraindicated in pregnancy, caution in those with heart failure Side affects headache, dizziness, constipation, bradycardia and AV block, peripheral edema, gingival hyperplasia Alpha-receptor blockers Alpha-beta blockers Alpha-agonists Management of blood pressure o Prehypertension no drug indicated o Stage I thiazide-type diuretics for most, may consider: ACE inhibitor, ARB, B-blocker, CCD or combination o Stage II 2-drug combination for most (usually thiazide-type diuretic and ACE inhibitor or ARB or Bblocker or CCB) Considerations regarding BP therapy Age Race Concomitant diseases and therapies Quality of life impact (side affects) Economic considerations Doses/day Special considerations One month of drug therapy: o BP below 140/90: continue drug therapy, lifestyle modifications, monitor every 6 months o No response or intolerable reactions: substitute drug from a different class, recheck in 1 month, continue lifestyle modifications o Drug well tolerated, goal not achieved (PP) Guidelines for Patients Receiving Anti-Hypertensive Drugs Closely monitor BP and pulse Weigh patient daily for 3-4 days after initiation of treatment Observe for drug intolerance Instruct patient to change positions slowly Emphasize importance of periodic follow up: not missing, doubling, discontinuing (PP)