Principles of Pharmacology PDF

**PRINCIPLES OF PHARMACOLOGY** **Basic terms** - Drug -- any chemical that affects living processes - Pharmacology -- study of drugs 7 their interactions w/ living systems - Clinical Pharmacology -- study of drugs in humans - Pharmacotherapeutics -- use of drugs to Dx, prevent or tr...

**PRINCIPLES OF PHARMACOLOGY** **Basic terms** - Drug -- any chemical that affects living processes - Pharmacology -- study of drugs 7 their interactions w/ living systems - Clinical Pharmacology -- study of drugs in humans - Pharmacotherapeutics -- use of drugs to Dx, prevent or treat disease or prevent pregnancy or simply the medical use of drugs **Properties of The IDEAL Drug** - **Most Important Properties: Effectiveness, Safety, / Selectivity: ** - All new drugs must be shown to be [effective] before release for marketing. - A [safe] drug cannot produce harmful effects -- all drugs can produce harmful effects but w/ proper dosing & selection, harm can be reduced. - A [selective] drug only elicits the response for which it is given; however, all drugs cause SE. - THEREFORE, NO SUCH THING AS A "PERFECT DRUG!" **More IDEAL Characteristics** - Reversible action - Predictability -- patients are unique & rxn to the drug cannot be predicted - Ease of administration - Freedom from drug interactions - Low cost -- \$4 generics vs \$\$\$\$ - Chemical stability -- even moisture can cause deterioration - Possession of a simple generic name -- "LOL" e.g. aspirin vs acetyl-salicylic acid,  **Therapeutic Objective** - Provide maximum benefit w/ minimal harm (because our patients are depending on us). - Multiple factors determine how a person will respond to a given dose of medication. **Pharmacokinetics** - All four phases of pharmacokinetics, absorption, distribution, metabolism, & excretion involve drug movement across cell membranes.   - The cell membrane is a double layer of phospholipids; therefore, the drugs must be lipid soluble. **Pharmacokinetics** These processes determine the amount of the administered drug that reaches its site of action. Four processes:  - **Drug absorption** - **Drug distribution** - **Drug metabolism** - **Drug excretion** Individual variations can influence the drug reaching its intended action site resulting in too little or too much response. E.g. kidney & liver impairment **Pharmacokinetics**: Pharmakon meaning poison & kinesis meaning motion **Three Mechanisms to cross membranes** - Passage through channels or pores, transport systems which are selective & can move drugs (some require energy), & P-glycol protein transporter system.  - This system can pump drugs into the bile, for elimination; kidney pumps into urine for excretion, in placenta pumps back into blood reducing fetal exposure.  **Passage of drugs across membranes** 3 ways for a drug to cross cell membrane - **[Channels / pores] --** only small ions such as K / Na - **[Transport systems]** -- drug structure determines transporter system, very selective; some systems require expenditure of energy / some do not.  - Transport moves drug from intestines to the blood; transport in the kidneys pump drug from the blood into the renal tubules for excretion. **[P-glycoprotein transporter]** moves drug OUT OF CELLS. E.g. liver, kidney, placenta, intestines, brain. - **[Direct penetration of the cell] membrane --** most drugs penetrate directly because they are too large or lack transport systems. Since cell membranes are composed of lipids usually, then the drugs must be lipid soluble to penetrate directly.  **Bioavailability** - **ability of drug to reach systemic circulation from its site of administration**; occurs primarily w/ oral preparations rather than w/ parenteral; tablet disintegration time, enteric coatings & sustained-release formulations, gastric pH, diarrhea, constipation & food in stomach all affect this **Absorption** - Definition: movement of drug from its site of administration into the bloodstream - Rate of absorption determines how soon action can begin. - Before absorption the drug must dissolve; liquids dissolve faster - Absorption depends on surface area, more surface area in intestine due to microvilli than in stomach - Faster blood flow, faster absorption (central vein vs periphery) - Highly lipid soluble drugs absorb faster since they can readily cross cell membranes **Dosage & Administration** - Many drugs have more than one indication (e.g. methotrexate) - The dosage may differ depending on the indication for which the drug is being used, e.g. aspirin - The dosage may differ depending on the route selected (e.g. morphine) - Be aware that certain drugs when given IV may cause severe local injury if extravasation occurs (e.g. dopamine) **Route:  Intravenous** - THE POSITIVE:  rapid onset, precise control, can use a large volume (e.g. 40 meq KCl in 1000 ml D5W); useful for emergencies, Tx when the oral is destroyed by gastric enzymes, e.g. insulin - THE NEGATIVE:  high cost, difficult, inconvenient, special training to place IV line; Irreversible once administered; slow administration to reduce r/o toxicity.  - Can cause fluid overload, infxn, embolism, must read labels carefully to avoid errors which are more common. (E.g. Regular insulin can be given IV / NPH insulin cannot; Epinephrine, different concentrations are given by different routes.) **IM/SubQ** - ADVANTAGES:  quick absorption but not as quick as IV (usually about 30 minutes.)  - Can be used for depot absorption e.g. depot penicillin G will last about a month - DISADVANTAGES:  can be painful, administration in just a few sites, bleeding risk, less convenient for oral. **Oral (po) (per os)** - Barriers to easy absorption & can be highly variable in absorption (e.g. Fosamax, thyroid, penicillin G) - Safer than other methods - Requires a conscious cooperative person, cannot administer to patients who are comatose, NPO, psychotic, seizuring, or nauseated **Oral Meds** - Tablets -- those made by different manufacturers can differ in rates of dissolution resulting in differences in bioavailability. - **Enteric coated tablets -- med will dissolve in intestines rather than stomach due to the "plastic" covering over the tablet -- can protect from irritating meds to the stomach or to protect the med from stomach acid.** (E.g. aspirin) - Sustained release -- filled w/ "beads" of meds / placed in a capsule **Other Routes** - Inhalation - Rectal - Vaginal - Topicals -- creams, eyes, ears, nose - Transdermal -- e.g. nitro - Heart, nerves, joints **Pharmacokinetics** - Once the drug reaches its receptor site, it will be bound to the receptor.  - The amount of binding can vary based on tolerance vs naivety (e.g. morphine), placebo effects, receptor impairment (e.g. T2DM), interference from other drugs (e.g. calcium, antacids can decrease absorption) - Individual variations can influence patient response **Protein Binding (Albumin)** - Only unbound free drug molecules can leave the vascular space since the bound molecules are too large to fit through the pores in the vascular space.  - Binding is reversible. % of drug bound at any given time is dependent on the strength of the attraction.  (E.g. Attraction between albumin & warfarin is strong (99%), while gentamicin is weak (10%).   - So only 1% of warfarin can be used by the tissues while 90% of gentamicin can be used.) **Drug Receptor Sites** - binding of the drug to its receptor; drugs are chemicals that produce effects by interacting w/ other chemical; receptors are special chemicals in the body that most drugs interact w/ to produce effects  **Receptor properties**: receptors are normal points of control of physiologic processes; function is regulated by molecules supplied by the body; drugs an only mimic or block the body's own regulatory molecules; drugs cannot give cells new functions **Drug Distribution** - Drugs are usually carried in the vascular space to the tissues, such things as abscesses & tumors can limit distribution since they don't have capillaries.  - Going to the actual tissue (exiting the vascular space) also can be limited by the **blood brain barrier (BBB) which requires drugs which are lipid soluble or have their own transport system to cross the barrier due to tight junctions between the cells**.  - BBB is not fully developed at birth & newborns have heightened sensitivity to meds that act on the brain.  - Also, the placenta acts as a barrier, but the above drugs can cross the barrier resulting in damage to the fetus.  **Naming Drugs**: Chemical, Generic, Brand **Drug PRE-Administration** - Pre-administration assessment (especially for new drugs or a new patient) - **[Using the NURSING PROCESS -- ASSESSMENT PHASE]** - Collect baseline information- ask the patient & or family what the name of the drug, the dosage, purpose, & timing is. E.g. losartan 50 mg qd in the AM for HTN; primidone 25 mg q three days at night to control hand tremors - Baseline info is needed to evaluate therapeutic responses & AE.  - Identify high risk patients: liver & or kidney impairment, genetic factors, drug allergies, pregnancy, older adult, pediatric age;  - Review patient hx, physical exam, & lab results - Assess patient ability for self-care, e.g. dementia, critical illness, depression - Assess patient knowledge of medications & for further education - Patient should know name of medication, dosage, route of admin., purpose of drug of all drugs he is taking including prescription. OTC, recreational (alcohol, nicotine, caffeine, illicit) - **Obtain list of drugs allergies & the actual type of rxn** **Drug Administration ** - Dosage size, route, / timing can help to determine drug response - Medication errors must be avoided - Patient adherence, especially at home, cannot be predicted. **Nurse Practice Act** - The nurse is legally responsible for any drugs administered/not administered. "Sins of omission / commission."  - The nurse must check the armband & 1^st^ against the medication administration record (MAR) before giving any medication, each & every time.   - **Asking the person to state their name is not enough.**  - The nurse must know the MOA, correct dosage, why the drug is being given, AE, correct route of administration, evaluation & documentation of patient response to each drug, & they are responsible for education of the patient/family before discharge.  **Routes of Drug administration** - IV: no barriers to absorption, quickly absorbs, acts quickly, is controllable & can infuse large number of drugs; disadvantages are irreversible, at r/f infxn, contamination/embolism, FVE  - IM: cap wall is barrier, rapid absorption, disadvantages are r/f injury, inconvenient & discomfort  - SubQ: same as IM - Oral: barriers are food in gut, other meds given, coatings / gastric pH; highly variable absorption pattern; first pass effect; a lot less expensive, reversible & safer than other routes - Others: topical, transdermal, inhaled, rectal, vaginal, direct injection to specific site  **Injection Routes**: angles to approach **Administration Action times**: Times for each route to work **Nursing Role in Changing Routes** - The patient is receiving Ampicillin 2 gms q8h but is choking on the tablets.   - What can/should the nurse do?  - What requires an order, what does not?  - The patient is receiving morphine sulfate 2-4 mg IV push for chest pain q1-2 hours PRN. The patient asks if he can receive it by mouth instead.   - What would the nurse do & say to the patient? - Demerol 75 mg IM for post-op pain q3-4h PRN. Give Vicodin (hydrocodone 5mg) q4h when tolerating orals.   **Metabolism of Drugs** - Also called biotransformation, which is the enzymatic alteration of drug structure. - Usually takes place in the liver. - Performed by the P450 hepatic microsomal enzyme system, also called cytochrome P450 - **Three cytochrome P450 enzymes are designated CYP1, CYP2, & CYP3 & they metabolize drugs specifically -- lots of interactions** - Drug metabolism most importantly results in drug excretion in the kidneys **Considerations in Drug Metabolism** - Age -- metabolism very limited in infants until about one year old. In older adults, metabolism is decreased & many times drug dosage needs to be decreased.  - **First Pass effect -- rapid hepatic inactivation of certain oral drugs; on initial GI absorption, carried directly to the liver via the portal vein; if the capacity of the liver to metabolize the drug is extremely high, then the drug can be completely inactivated, & no therapeutic effects will occur**.  - In some cases, these drugs are initially given parenterally which allows for bypassing the liver.  E.g. Nitro (giving SL nitro is very active). **Drug Excretion** - Removal of drugs from the body through urine, bile, seat, saliva, breast milk, & expired air. Most important is the kidney! **Time course of drug responses** - Absorption, distribution, metabolism & excretion determines how much drug will be at its action site at any given time.  **Drug Half-Life** - time it takes for drug to be reduced by 50%; short half-life leaves body quickly & long half-life leaves body slowly; determines dosing intervals **Drug Binding** - **Agonists are drugs that activate or turn on receptor sites** (e.g. dobutamine mimics the effect of norepinephrine at cardiac receptor sites) -- **Has both efficacy & affinity** - **Antagonists are drugs that prevent receptor sites from being activated**, e.g. antihistamines suppress allergy rxns such as sneezing by binding to histamine (H~1~) receptors.  E.g. Benadryl **Drug-Drug Interactions** - interactions can occur whenever patient takes more than one drug; some interactions are intended & desired or unintended or undesired; patients frequently take more than one drug to either treat one disorder or have multiple disorders that need drugs; OTC meds, caffeine, nicotine, alcohol can also have interactions  **Recognition & Avoidance of Drug-Drug Interactions** - Can have intensified therapeutic & AE, reduction of therapeutic & AE or can create a unique response - Direct chemical & physical interaction, pharmacokinetic interaction, pharmacodynamics interaction or combined toxicity - **Clinical significance**: have potential to significantly alter outcome of therapy; responses may be increased or decreased; the risk is increased when you take more drugs; interactions are especially important for drugs w/ low therapeutic indexes; many interactions have not been identified  **Therapeutic Index** - **measure of drug's safety**; defined as LD50: ED50 ratio; ED50 is dose that is required to produce a defined therapeutic response in 50% of population; LD50 is dose that is lethal to 50% of animals treated; large therapeutic index indicates that a drug is relatively safe; low therapeutic index is not safe **Drugs that stimulate the synthesis of CYP isoenzymes are inducing agents; Inhibitors increase the drug levels of the other drug** **P450 drugs** **Drug-Food Interactions** - **Grapefruit w/ statins & calcium channel blockers** - Greens w/ warfarin - Theophylline w/ caffeine - Potassium sparing diuretics w/ potassium salt substitutes - Aluminum containing antacids (Maalox) plus orange juice (Increase absorption of Maalox).  **Adverse Drug rxns & Medication errors** - Adverse drug rxn is any noxious, unintended, & undesired effect that occurs at normal drug doses.  - Range in intensity to mildly annoying to life threatening **Side Effects** - Nearly unavoidable secondary drug effect produced at therapeutic doses (e.g. drowsiness caused by antihistamines) - Generally predictable & intensity is dose dependent.   - SE may occur soon after starting med or much later.  **Toxicity**: Degree of detrimental physiologic effect caused by excessive drug dosing, e.g. Morphine- coma, insulin- hypoglycemia,  **Allergic Rxn** - **Immune response that occurs once prior sensitization occurs. ** - **Can be mild to life threatening.  ** - **The intensity is the result of the immune system not the drug dosage. ** - **Use Epi for Anaphylaxis** **Idiosyncratic Effect** - Uncommon drug response usually resulting from a genetic or unknown predisposition (e.g. G6PD deficiency will cause hemolysis after taking aspirin or sulfonamides) **Medication Reconciliation** - **Should be conducted whenever a transition in care occurs, hospital admission, discharge, moving to a different level of care in the hospital. ** - **Make a list of the current meds -- name, indication, route, dosage, & dosing interval. ** - **Include vit., herbal products, prescription, nonprescription, legal, illegal. (home) ** - **Make a list of meds for the new place (hospital)** **Medication Errors** - **Med Error**: risk for error in hospitals is high because each medication order is processes by several people; nurse is last person in this sequence & the nurse is the last line of defense against mistakes; places heavy responsibility on nurse to ensure patient safety; 90% of drug errors are due to human factors  - **Ways to reduce**: help encourage patients & their families to be active & informed members of healthcare team; create institutional culture that is dedicated to safety; give healthcare providers tools & information they need to prescribe, dispense & administer drugs as safely as possible; institute safety checklists for high-alert drugs (about 20 drugs cause 80% of med error related deaths)  - **How to report**: MER program; confidential & can be done by phone, fax or internet; program encourages all healthcare providers to report errors; all info is forwarded to FDA & ISMP & product manufacturer - Reporting helps to improve patient safety by increasing our knowledge of causes of med errors.