Pharmacology Exam 1

Pharmacology

study of drugs that alter functions of living organisms

Pharmacotherapy

use of drugs to prevent diagnose, or treat signs, symptoms, and disease processes

Medications

drugs given for therapeutic purposes

Local medication effect

act mainly on site of application

Systemic

taken into the body, circulated via the bloodstream to sites of action, and eventually eliminated from the body

Drug sources

• plants

• animals

• minerals

• synthetic compounds

Synthetic

completely made in a lab

Semisynthetic

lab + natural

Drug Classifications

classified according to effects on body systems, therapeutic uses, and/or chemical characteristics
(may fit into multiple categories)

Prototypes

individual drugs that represents groups of drugs (usually first drug in group to be developed)

Generic name

chemical or official name

Trade name

brand name

Prescription

written by a licensed healthcare provider

Over the Counter (OTC)

• no prescription necessary

• regulated by various laws

Food, Drug & Cosmetic Act of 1938

Regulated that official drugs meet standards of purity and strength

Comprehensive Drug Abuse Prevention and Control Act

• Passed in 1970

• Title II: Controlled substances act

• Regulates manufacturing and distribution of narcotics, depressants, stimulants, hallucinogens, and anabolic steroids

Drug Enforcement Administration

• Enforces controlled substances act

• Registers individuals and companies legally empowered to handle controlled substances

• Regulates documentation and handling of controlled substances

US Food and Drug Administration (FDA)

• Responsible for ensuring safety and efficacy of drugs before they can be marketed

• Since 1962, specific testing standards must be applied

• runs clinical trials (monitored by CDER) - phases 1 to 4

• approves many new drugs annually

• may change status from prescription to OTC

Controlled Substances

Schedule I to Schedule IV

Schedule I

No medical use, drugs such as heroin

Schedule II

prescribed drugs with high potential for abuse, such as morphine

Schedule III

drugs with moderate to low potential for physical and psychological dependence

Schedule IV

controlled substances with a low potential for abuse and dependence

Schedule V

lowest abuse potential of all controlled substances

Rights of Medication Administration

patient, med, dose, route, time, reason

National Patient Safety Goals

establishes a do not use list of unacceptable abbreviations and targeted high risk activity

The Institute for Safe Medication Practices

• high alert meds

• pregnancy info, risk summary and clinical considerations

• beers criteria (meds to avoid in older adults)

Pharmokinetics

what the body does to the drug

Pharmacodynamics

what the drug does to the body, drug actions on target cells and body systems

Lipid-soluble drugs

dissolve in the lipid layer of the cell membrane and diffuse into or out of the cell

Gated channels

regulate movement of ions

Carrier proteins

attach to drug molecules and move them across cell membranes

Pharmokinetics steps

absorption, distrubution, metabolism, excretion

Absorption

oral drug is swallowed and enters stomach

• dissolves to cross cell membranes

• moves into small intestine

• crosses cell membranes into the bloodstream

Do Not Crush

• SR

• LA

• ER, XL or XR

• CR

• DR

Oral Route

slowest route of entry

Inhalation

fast route to brain

Intravenous

takes effect within seconds, 100% bioavailable (bypasses the liver & intestines)

Transdermal

released into bloodstream over several hours

Intramuscular

Epipens or vaccines

Bioavailable drug

Amount of drug that is distributed to the rest of the body in an unchanged form (varies by drug)

High First Pass Effect

low bioavailbility

Protein Binding

Plasma proteins act as carriers for drug modules. Bound drugs stay in the bloodstream and is pharmacologically inactive. The free drug can leave the blood stream and act on body cells.

Cytochrome P450 (CYP)

in liver, metabolizes most drugs

CYP450 Enzyme Inducers

increase the enzymes from the liver

• example: St. John’s wort

CYP450 Enzyme Inhibitors

reduce the enzymes from liver

• example: grapefruit

Excretion routes

• kidneys

• biliary (feces)

• liver

• other (sweat, lungs)

Drug Half Life

time for concentration of a drug to be reduced by 50%

• determined by metabolism and excretion

Receptor Theory of Drug Action

drugs chemically bind with receptor sites causing

• activation, inactivation or alteration of intracellular enzymes

• changes in permeability of cell membranes to one or more ions

• modification of the synthesis, release or inactivation of neurohormone

Agonist

drugs that produce effects similar to naturally occuring neurotransmitters and hormones - accelerate or slow normal cell processes

Antagonist

blocks a response by occupying receptor site

Nonreceptor drug action

• antacids

• osmotic diuretics

• several anti-cancer drugs

• metal chelating agents

Variables Impacting Drug Action

drug related variables: dose, route/formation, drug-diet, drug-drug

Person Related Variables that Impact Drug Actions

• age

• body composition

• pharmacogenomics (genetics, ethnicity, sex)

• psychological considerations

• tolerance and cross-tolerance

Peak Drug Level

highest plasma concentration of drug at a specific time, indicating the rate of absorption

• blood sample should be drawn at the proposed peak time, according to the route of administration

Trough Drug Level

lowest plasma concentration of a drug, measures the rate at which the drug is eliminated

• blood sample should be drawn immediately before the next dose of drug is given, regardless of route of administration

Adverse Effects of Drugs

any undesired responses to medication administration

• all drugs can produce these

• can occur with usual therapeutic dosing

• more likely to occur to be more severe with high or IV dosing

• especially likely to occur with high alert drugs and in neonates, infants, or older adults or in people who take multiple drugs

Interactions that increase theraputic or adverse drug effects

• additive effects or synergism

• interference with metabolism

• displacement

Interactions that can decrease drug effects

• antidote medication

• decreased intestinal absorption of drugs

• increased metabolism rate of drugs

• compete for same receptors

• drug and diet (warfarin and vitamin K)

Drug Overdose

• results from excessive amounts of medication

• may damage body tissues

• may result from single large dose or prolonged ingestion of smaller doses

• may involve alcohol, prescription, OTC or illicit drugs

• can be a medical emergency

Acetominophen antidote

acetylcystine

Calcium Channel Blocker Antidote

Calcium Gluconate

Heparin Antidote

Protamine Sulfate

Warfarin Antidote

Vitamin K

Opioid Antidote

Naloxone

Beta Blocker Antidote

Glucagon

Inflammation

triggered by cell or tissue damage or dead cells/noxious stimuli like bacteria

1. vascular stage

2. cellular stage

Vascular Stage of Inflammation

vasodilation bringing blood to site (redness, swelling, heat, pain, loss of function) - clotting

Cellular Stage of Inflammation

leukocytes move to area of injury into tissue and engulf bacteria/cellular debris during phagocytosis - products are exudates

Histamine

• highly concentrated in mast cells, basophils, platelets

• causes vasodilation

• increases capillary and venule permeability

• stimulates nerve endings to cause pain

• stimulate movement of eosinophils into injured tissue

Bradykinin

• becomes activated with tissue injury

• WBCs ingest damaged cells in injured tissue and release enzymes that activate kinins

• activated kinins prolong the vasodilation and vascular permeability caused by histamine (erythema, heat, pain)

• stimulate pain nerve endings

• cause mucous secretion

Complement

group of plasma proteins that destroy cell membranes and pathogens

• cause vasodilation and vascular permeability

• promote movement of WBCs into the area (chemotaxis)

Cytokines

interferons and interleukins that act locally and systemically

• chemotaxis of WBC

• inflammatory response

• fever

Prostaglandins

found in most body systems, made up of COX-1 and COX-2 enzymes

COX-1 Enzymes

prostaglandins that protect the GI tract, platelets, kidneys and smooth muscle

COX-2 Enzymes

prostaglandins that increase inflammation (vasodilation, edema, pain, fever)

Osteoarthritis

Degradation of articular cartilage, bone and synovium (primary and secondary)

Primary Osteoarthirtis

no history injury

Secondary osteoarthiritis

due to previous injury or inflammatory condition

Clinical Manifestations of Osteoarthiritis

• pain

• stiffness

• joint instability

Pathophysiology of Rheumatoid Arthiritis

• inflammation of synovium —> swelling + joint damage

• endothelium activates chemotactic factors

• leukocytes attract to joint spaces

• autoimmune response exaggerated in genetically susceptible individuals

• formation of antibody-antigen complexes, activate complement, T-cells

• unregulated immune response

Drugs Used for Pain, Fever and Inflammation

• acetominophen

• aspirin

• NSAIDS

Salicylates

• acetylsalicylic acid (ASA)

• salsalate

Salicylates

act both centrally and peripherally to block the transmission of pain impulses, inhibits prostaglandin synthesis

• reduce fever by acting on hypothalamus

• diminish inflammation (OA & RA)

• low doses suppress platelet aggregation

• pregnant persons at risk for preeclampsia

• low dose indicated for management of ischemic stroke, transient ichemic attack, angina and acute myocardial infection

Aspirin Contradictions

• low dose aspirin (75-81 mg up to 325 mg) is given to reduce risk of MI or TIA

• non-enteric coated tablet 160mg - 325mg chewed or crushed as soon as acute MI is suspected

• Antipyretic - adults only!

• Contradicted: childen + adolescents - Reye Syndrome

Salicylate Poisoning or Overdose

• tinnitus, hearing difficulty

• headache, confusion, drowsiness, vertigo, sweating

• early: respiratory alkalosis due to hyperventilation

• later: respiratory depression and acidosis

• fluid and electrolyte imbalance

• nausea, vomiting, fever

Acetaminophen Uses

mild pain and fever

Acetaminophen Mechanism of Action

• may relieve fever through central action in the hypothalamic heat-regulating center

• may inhibit pain sensitizers at pain receptors in the periphery

Acetaminophen Contraindications

• liver failure

• use of other over-the-counter (OTC) products that contain acetaminophen

Acetaminophen Cautions

• patients with liver disease

• G6PD deficiency

• chronic malnutrition

• long-term alcohol use

• severe hypovolemia

• severe renal impairment

First Generation NSAIDS

inhibits COX-1 and COX-2

• Ibuprofen

• Naproxen

• Indomethacin

• Ketorolac

• Meloxicam

• Piroxicam

Second Generation

Primarily inhibit COX-2

• Celecoxib (Celebrex)

NSAIDs Mechanism of Action

• inhibit prosaglandin synthesis in CNS and PNS

• inhibit COX-1 and COX-2 enzymes

• relieve pain by acting centrally and peripherally to block pain impulse transmission

Propionic acid derivatives: Ibuprofen

inhibits prostaglandin synthesis in both the central and peripheral nervous systems

Acetic acid derivatives: Indomethacin

strong anti-inflammatory effects and more severe adverse effects than the propionic acid derivatives

Selective COX-2 Inhibitor: Celecoxib

selectively block production of prostaglandins associated with pain and inflammation without blocking those associated with protective effects on gastric mucosa, renal function and platelet aggregation

Ibuprofen Uses

• osteoarthritis

• rheumatoid arthiritis

• dysmenorrhea

• fever

• headache

Ibuprofen Mechanism of Action

inhibits formation and release of prostaglandin by inhibiting cyclogenase (COX) enzymes - suppresses inflammation

Ibuprofen Contraindications

• GI ulcer

• GI bleed

• post-CABG

• pregnant women > 20 weeks gestation = fetal harm

Ibuprofen Black Box Warning

may increase risk of MI or stroke (more risk with higher doses)