Better living through pharmacology, pharmokinetics, and pharmodynamics,P. Andrews

CAREFUL AND JUDICIOUS USE OF MEDICATIONS CAN TRULY MAKE A DIFFERENCE

Things to know about drugs Pharmokinetics Pharmodynamics Generic names Trade names Schedules of drugs FDA approval

process The Harrison

Narcotic act of 1914

Enteral drug administration

Parenteral drug administration

Mechanism of action

Route of administration

Pure food and drug act of 1906

Things to know, cont. The Federal Food,

Drug and Cosmetic act of 1938

The Durham-Humphrey Amendments to the 1938 Act

The Controlled Substance Act of 1970

OTC medications Absorption Six rights of

medication administration

Bioavailability Biotransformation First-pass effect

More things to know!

Blood-brain barrier Placental barrier Oxidation Hydrolysis Elimination Agonist Antagonist Agonist-antagonist Extrapyramidal

symptoms

Idiosyncratic response

Tolerence Side effect Cumulative effect Synergism Potentiation Onset of action Therapeutic index Half-life Minimum effective

concentration

Historical trends

Ancient health care Herbs & minerals - 2,000 BC Pharmacology by end of

Renaissance; separate from medicine

Vaccinations 1796 (Smallpox) Insulin, Penicillin early 20th

century Modern health care

Human insulin tPA

Pharmacology

Chemical name Precise description chemical composition

and molecular structure Vecuronium Bromide:

Chemical compound: piperidinum, 1-[(2, 3, 5, 16, 17)-3, 17-bis (acetyloxy)-2-(1-piperidinyl)androstan-16yl]-1-methyl-, bromide.

Molecular structure C34H57BrN2O4

Generic name – Non-proprietary name

FDA approved First manufacturer

vecuronium bromide Trade (Proprietary) name

Registered to a specific manufacturer Marsam Pharmaceuticals, Inc. Vecuronium TM

Official name Assigned by USP

Vecuronium Bromide USP

Drug Sources

Plants Atropine – Deadly

nightshade plant Morphine –

Opium plant Digitalis –

Foxglove Animals and

Humans Insulin Glucagon

Minerals Calcium chloride Sodium

Bicarbonate Magnesium

Sulfate Synthetics

Bretylium tosylate

Lidocaine Procainamide

Drug Profiles

Names Classification Mechanism of Action Indications Pharmacokinetics Side effects/ adverse reactions Routes of administration Contraindications Dosage How supplied Special considerations

Legal stuff- Federal

Protect the public Pure Food and Drug Act, 1906

Improve quality and labeling of drugs

Harrison Narcotic Act, 1914 Regulating importation, manufacture,

sale, use of opium, cocaine, derivatives

Federal Food, Drug, Cosmetic Act, 1938 Empowers FDA to enforce, set

premarket safety standards

More Federal stuff

Durham-Humphrey Amendments, 1951 Prescription drug amendments, 1938

act; requires written or verbal prescription from physician to dispense some drugs

Created OTC category

Comprehensive Drug Abuse Prevention & Control Act, 1970 (Controlled substance act) Replaces Harrison Narcotic Act Establishes 5 schedules of drugs Prohibits refilling of Rx for

Schedule II drugs, & requires original Rx to be filled within 72 hours

Other regulations

Prescription drugs Designated sufficiently dangerous to

require supervision OTC

Available in small doses; present low risk

General issues

Drugs must be secured

State laws vary; generally set scope of practice for EMS

Medical directors can delegate authority to paramedics

New Drug Development

You Are Responsible!

Know precautions and contraindications

Practice proper technique

Know how to observe and document effects

Establish and maintain professional relationships with other health care providers

In disease, all systems are affected The three systems can’t exist

without each other The actions of one impact the actions

of the others I.e., stress (nervous system) disrupts

endocrine system which may respond with glucocorticoid production = suppressed immune response

Drug Class Examples

Nitroglycerin Body system: “Cardiac drug” Action of the agent: “Anti-anginal” Mechanism of action: “Vasodilator”

Indications for nitroglycerin Cardiac chest pain Pulmonary edema Hypertensive crisis

Which drug class best describes this drug?

Understand pharmacokinetics, pharmacodynamics

Have current references available

Take careful drug histories Evaluate compliance, dosage,

adverse reactions Consult with medical direction

when appropriate

SIX RIGHTS OF MEDICATION ADMINISTRATION

Right medication Right dose Right time Right route Right patient Right documentation AND SEVEN – Right to refuse

Cells talk to each other

Three distinct languages Nervous system

neurotransmitters Endocrine system

hormones Immune system

cytokines

Another way to classify drugs Mechanism of Action

Drugs in each category work on similar sites in the body and will have similar specific effects/side effects

Example: beta blocker actions and impacts Suppress the actions of the sympathetic

nervous system Prehospital administration of epinephrine

may not produce as dramatic effects with a patient taking a drug in this class

Prehospital example: Hyperglycemics Dextrose 50% and glucagon

Both will raise blood glucose Mechanism of action

Glucagon: hormone that works in the liver to convert stored chains of carbohydrate to glucose

Dextrose 50%: ready-made simple sugar that is ready to enter into the cell

Which drug is considered first-line for hypoglycemia? Why?

What are some limitations for glucagon in the presence of severe hypoglycemia?

Sources of drug information

On-line - be cautious of source Pharmacy.com Medline.com

AMA Drug Evaluation Physician’s Desk Reference (PDR) Hospital Formulary Drug Inserts Other sources

Controlled substances

Schedule I. High potential for abuse; no accepted medical indications Heroin, LSD, Crack, Marijuana

Schedule II. High potential for abuse, but have accepted medical indications Morphine, Fentanyl, meperidine,

Dilaudid, Oxycodone, Cocaine, Codeine, Opium, Methadone

Schedule III. Less potential for abuse, and accepted medical indications Tylenol #3, Vicodin

Schedule IV. Low potential for abuse, but may cause physical or psychological dependence. diazepam, midazolam, butorphanol,

lorazepam, Phenobarbital

Schedule V. Low potential for abuse, but have small quantities of narcotics Cough medicine (Vicks 44)

Standardization of Drugs

A necessity Techniques for measuring a

drug’s strength and purity Assay Bioassay

The United States Pharmacopeia (USP) Official volumes of drug

standards

Medical Control

Medication administration is ALS skill Medical Director

Actively involved in and ultimately responsible for all clinical and patient care.

We are extension of physician’s license

Special Considerations- Pregnant patients

Evaluate benefit vs. risk to fetus

FDA has a scale (A,B,C,D,X) to indicate drugs that may have documented problems

Many drugs are unknown to cause problems

Drugs may cross placental barrier or through lactation

FDA Pregnancy Categories

A Adequate studies have not demonstrated a risk to the fetus

B Animal studies have not demonstrated a risk to the fetus; no adequate studies in humans OR

Adequate studies in pregnant women have not demonstrated a risk to fetus in first and last trimester BUT animal studies show adverse effects

FDA Pregnancy Categories, cont.C Animal studies have demonstrated

adverse effects, but there are no adequate studies in pregnant woman

D Fetal risk has been demonstrated; in certain circumstances, benefits could outweigh risks

X Fetal risk has been demonstrated. This risk outweighs any possible benefit to mother. Avoid using in pregnant patients.

Special Considerations – Pediatric patients

Based on weight or BSA Length-based resuscitation tape

(Broslow’s) Absorption of oral meds less due

to differences in gastric pH, emptying time, low enzyme levels

Pediatrics, cont.

Unexpected toxicity common in topically applied meds

Drugs that bind to protein have higher availability

Neonates have much higher % of extracellular fluid – may require higher doses

Lower metabolic rate & hepatic system ; higher risk for toxicity

Figure 6-1 A Broselow tape is useful for calculating drug dosages for pediatric patients.

Special Considerations - Geriatric patients

MULTIPLE MEDS A PROBLEM Physiological effects of aging can lead

to altered pharmacodynamics and pharmacokinetics. Absorb oral meds slower Distribution altered Lipid soluble drugs have greater deposition Drug action delayed or prolonged

Pharmacology

The study of drugs and their interactions with the body

Drugs do not confer any new properties on cells or tissues – only modify or exploit existing functions

Given for local or systemic action

Pharmacokinetics

The study of the basic processes that determine duration and intensity of a drug’s effect

Transport

Active transport Requires energy to move a substance ATP ADP Sodium – potassium pump Facilitated diffusion

Binds with carrier protein, configuration of cell membrane changes, allows large molecule to enter body

I.e., Insulin increases glucose transport from 10-20 fold

Transport, cont

Passive transportmovement of substance without energy

Diffusion Movement of solute in solvent

Osmosis Movement of solvent

Filtration Molecules move across membrane

down pressure gradient

Absorption

IM faster than SC Enteral administration; must survive

digestive process Enteric coating; dissolve in duodenum

Many drugs ionize Ionized drugs don’t absorb across cell

membranes Most drugs reach equilibrium pH affects ionization

Concentration affects absorption Loading dose – maintenance dose

Bioavailability Amount of drug still active after reaching

target tissue

Distribution

Some drugs bind to proteins in blood and remain for prolonged period

Therapeutic effects due to unbound portion of drug in blood

Drug bound to plasma proteins can’t cross membranes

Changing blood pH can affect protein-binding action of drug.

TCA’s are strongly bound to plasma proteins.