Week 1: General Principles of Pharmacology

Chapter 1: Orientation to Pharmacology; Chapter 2: Application of Pharmacology in Nursing Practice; Chapter 3: Drug Regulation, Development, Names and Information; Chapter 4: Pharmacokinetics; Chapter 5: Pharmacodynamics

Pharmacology

Study of medications or dugs (which is any chemical that can affect a living system)

Pharmacokinetics

Movement of drug through the body (ADME)

Pharmacodynamics

What the drugs do to the body (molecular/cellular level)

The Perfect Drug

Effective

Safe

Selectiveand reversible

5 Rights

Right Patient

Right Medication

Right Dose

Right Time

Right RouteThe 5 Rights of medication administration are essential principles that ensure patient safety by verifying the correct patient receives the appropriate medication at the correct dose, time, and route.

Special Populations

Pregnancy, elderly, children

Pregnancy

About 2/3 patients take at least 1 med

Most drugs have not been tested during pregnancy & essentially all drugs can cross the placenta & enter breast milk (but to varying degrees)

Teratogenic meds are risky for pregnant patients

Elderly

65 & up

Decreased organ function

Polypharmacy

Co-morbidities

Aderence

Beers Criteria

Beers Criteria

Meds where side effects outweigh the benefits for geriatrics

Anticholinergic Beer Criteria

First-generation antihistamines - Commonly prescribed to elderly following ED admission

GI antispasmodics

CV Beers Criteria

Alpa-1 beta blockers (as antihypertensives)

Centrally acting alpha-2 agonists

Many antiarrhytmics

CNS Beers Criteria

TCAs

Antipsychotics

Barbiturates, benzodiazepines & other hypnotics

Endocrine Beers Criteria

Long-acting sulfonylureas

Sliding-scale insulin

Pain Beers Criteria

Skeletal muscle relaxants - Commonly prescribed to elderly following ED admission

Nonselective NSAIDs

Pediatric

16 & under

Pediatric meds often use weight-based dosing

KIDs List

Meds where side effects outweigh benefits for pediatrics

Ex: dopamine agonists (haloperidol)

Adverse Drug Reactions

Umbrella term for side effects and toxicity

Side Effects

Nearly unavoidable secondary drug effect produced at therapuetic doses

Generally predictable, higher dose means greater side effect, usually mild

Toxicity

Severe degree of detrimental physiologic effect (traditionally by excessive drug dosing)

Used interchangeably with severe ADR, regardless of dosing. Ex: cancer treatment causes neutropenia at normal dosing

Allergic Reaction

Trigger response from sensitive immune system, penicillin’s common

Carcinogenic Effect

Med may cause cancer; ironically cancer treatment meds are most common, like cyclophosphamide

Paradoxical Effect

Opposite effect than expected, like insomnia and restless from benzodiazepines

Iatrogenic Disease

Effect caused by the meds, like the side effect of parkinsonism from antipsychotic drugs

Physical Dependenece

Adaption to drug exposure, that abstinence will cause negative effects, most common with opiods

Idiosyncratic Effect

Effects due to generic predisposition, likw G6PD enzyme deficiencym will have problem with asprin

Teratogenic Effect

Drug-induced birth defect

Hepatotoxic Drugs

Drugs toxic to liver because they undergo metabolism and produce toxic metabolites

Check hepatic labs first and consider special population before administering

Hepatotoxic Antiseizure Drugs

Carbanazeoine (Tegretol)

Felbamate (Felbatol)

Phenytoin (Dilantin)

Valproic acid (Depakene, others)

Hepatotoxic Antidepressant/Antiopsychotic Drugs

Buproprion (Wellbutrin, Zyban)

Duloxetine (Cymbalta)

Nefazodone

Trazodone

TCAs

Controlled Substances Act

Five categories with potential for abuse

Schedule I: no medical benefit, high risk for abuse, eg heroin and marijuana

II-V have some medical benefit, and declining risk for abuse

ADME

Absorption (site of administration → blood)

Distribution (blood → tissue/cells)

Metabolism (alteration of drug by enzymes, mostly by liver, not all drugs do this, usually to turn lipid soluble drug into water soluble metabolite)

Excretion (removal of drugs from body, most commonly through urine)

How Drugs Get Across Cell Membranes

Lipoohilic or nonpolar or hydrophobic go through membrane

Hydrophobic move out of body

(water is polar and charged)

Routes of Drug Administration

Enteral - by way of the intestines (PO)

Parenteral - occuring outside the intestines (IV, shots, nebulizer)

PO Disadvantages

Bioavailability - how much makes it to the cell?

IV

Bypass absorption, fast acting, bioavailabilit, increased risk of ASE/toxicity

What happens to oral medication once in the body?

Absorbed from GI tract into bloodstream, mostly at small intestine beacuse of its surface area. Travels through portal vein into the liver.

Bioavailability

How much of active drug reaches bloodstream

While some meds cannot be taken orally because will be completely broken down in GI tract, others undergo extensive inactivation in the liver → first pass effect. Morphine, for example

Sublingial and rectum do not go through up the hepatic portal

Distribution

Once the drug is in the bloodstream, this describes how it moves throughout the body

Is there good blood flow?

Fat or bone sequestration, redistribution back into blood when blood levels of drug are low

Increased body fat, especially in older adults, provides storage for fat soluble meds (like a beta blcoker), so less present in plasma

Metabolism

Biotransofrmation = enzymatic alteration of drug structure

Lipophilic drugs more difficult to eliminate from the body, so metabolized to become more polar (lipophobic, hydrophilic)

Cytochrome P450

Used when taking more than one drug

If physiology or another substance inhibits the metabolism of this enzyme, there is a risk of more effect of the drug (propranolol)

If something induces metabolism of the enzyme, there is a risk of less effect of the drug (propranolol)

Prodrugs

Example of drug metabolized to “turn on” in liver vs most other times the metabolization is prepare the drug for elimination (lipid soluble drug gets turned into a water soluble metabolite)

Excretion

Often excreted in original form (most common for hydrophilic meds)

Mostly renal, next biliary/fecal, then breastmilk, sweat, saliva, tears, lungs

Therapeutic Range

Concentration in plasma that delievrs desired effect without adverse effects

Takes 3-5 half-lifes to reach

Loading Dose

Large firsst dose and then smaller maintenance dose, so we get to therapeutic range faster, called IV bolus for IV administration

Therapeutic Index

Lethal dose of 50% of people / effective dose of 50% of people

Higher therapuetic index, the safer the drug

Narrow therapeutic index indicates higher risk of toxicity

Dose-Response Relationship

More med = more response, but at phase 3 we reach saturation response

Maximal Efficacy

The height of the curve (dose x response) is the highest effect of drug, but we don’t always want that

Relative Potency

Amount of drug that must be given to produce desired effect

Drug-Receptor Interactions

Most drugs act by binding to a receptor/enzyme

Drug competes with endogenous (ligand) chemical that normally binds to receptor (block or inhibit) or mimic the effect of the endogenous substance to increase effect

Affinity

The more selective a drug is for a specific receptor, the less side effectd we will have

A drug with a high intrinsic activity (ability to activate receptor upon binding) and high affinity (strength of bond) would be great for mimicking endogenous ligand. Drug with low intrinsic activity and high affinity would be great for blocking endogenous ligand.

Agonists

Activste receptors, high affinity, high intrinsic

Antagonists

Blocks receptors

Competitive Antagonists

Reversible (more common)

Noncompetitive Antagonists

Irreversible (not forever, receptors broken down & replaced)

Dynamics

Continuous exposure to an agonist might cause down regulation or desensitization or tolerance (opiods)

Continuous exposre to an antagonist might cause up-regulation or hypersensitization

Drugs that Don’t Involve Receptors

Simple chemical reaction with other small molecules in body

Antacids (change pH of stomach contents), antiseptics (kill microorganisms), saline laxatives (create osmotic gradient to increase bowel movement and soften stool), and chelating agents (binds to metal ions to remove toxic metal from body)