Chapter 2 pharmacology continued....

Drugs excreted in saliva and swallowed and excreted intestinally

Via the human gastrointestinal tract

Women may be more sensitive, pregnancy avoid teratogenic drugs

if I administer phenobarbital to a client taking warfarin what would be the effect?…..

Carried out by microsomal or cytochrome P-450 enzymes (aka. Mixed-function oxidases) in the liver

Phase 2 reactions: The enzyme that mediates the conjugation are termed _____

CLINICAL PHARMACOKINETICS: KINETICS-__________ representation of how the drug is eliminated from the body

Most common, disruption in metabolism will increase active drug in blood

Half-Life(t ½): Is the amount of ___ that passes for its CONCENTRATION TO FALL TO HALF (50%) of its original blood level

Breast milk/sweat

First-order kinetics involve aspirin and alcohol (slide 43)

Metabolism (Biotransformation): Produces compounds that are ______ and more easily excreted

CLINICAL PHARMACOKINETICS: KINETICS- involves which of the following?

Morphine needs _____ oral dosage to give the same effect if given parenterally

Acid urine: tubular urine is more acid, weak acids are excreted more _____ and weak bases are excreted rapidly.

Suppositories, cream/enemas; Used if patient is vomiting/unconscious; For local (hemorrhoids) or systemic (antiemetic)

Route of choice for emergency situation; Disadvantage; phlebitis, irretrievability, allergy & side effects

Poorly absorbed; Poor patient acceptance

Disease patient may respond differently; Hyperthyroidism extremely sensitive to toxic effects of epinephrine

Metabolite=less polar/lipid insoluble→renal reabsorption→ _______ because reabsorption favors lipid soluble metabolites

Metabolism (Biotransformation): First pass effect; before circulating systemic circulation

_____ is the most common aka. GLUCURONIDATION, allows the body to convert a lipid soluble drug to a more polar compound

Select characteristic's of the oral route:

Glomerular filtration: Bound drugs can be filtered and remain in systemic circulation

Advantage of the oral route- causes stomach/intestinal irritation; nausea/vomiting; insulin inactive by GI acidity

The liver→ excretion

Drugs→Intestine→distribute through serum→pass to specific/non specific sites of action→liver (metabolized)→kidneys

Metabolites formed in the liver excreted via bile into the intestinal tract than eliminated by feces

It takes about 4-5 half lives of repeated dosing to build up to a steady state (level amount) in the body

Most rapid response, immediate onset; Absorption phase bypassed its into the blood already! Predictable response

The most common way for a drug to metabolize is "Inactive to active"

Active forms another active metabolite & then converted to inactive. This allows for action of the drug to be prolonged

Glucuronic acid is easily absorbed

The rectal route has the most sudden/rapid/immediate onset

Lack of knowledge or motivation

Phase 2 Reactions Involve conjugation with which of the following agents?

Metabolite is less polar and lipid soluble

Factors that Alter Drug Effects: attitude of provider, placebo drugs client perception

Select characteristic's of the oral route:

Metabolites less likely to bind to proteins and store in fat tissue; Metabolism enzyme-dependent process

The renal route of excretion can include which of the following?

Metabolism (Biotransformation): First pass effect; amount of drug to make a systemic effect is increased

CLINICAL PHARMACOKINETICS: ______-LIFE (t ___)

Gases used in general anaesthesia excreted via lung tissue by simple diffusion. So is ALCOHOL! You can SMELL alcohol!

The 3 ways a drug metabolizes are?

From routes outside the GI tract, such as intravenous routes

For long half-life drugs once discontinued its effect can take several ___ to dissipate

Time of effect

Cytochrome P-450: This can be _____ to speed up drug metabolism or _______ to reduce or slow down drug metabolism

Drug from site of action to nonspecific site of action; Drug gets TERMINATED if goes to nonspecific site

There are ____ Ways Drug Metabolize

Routes of Administration and Dose Forms: affects which of the following?

Elderly degenerating organs, child dosage v.s adult dosage

Smoking induces enzymes so ↑ dose of benzodiazepines (Valium, Xanax)psychoactive drug are needed, pesticides/solvents

(ie. diazepam (Valium) antianxiety metabolized into desmethyldiazepam→total effect of both drugs, longer duration

Thiopental→ goes to CNS (sleep), redistributed to muscle (terminated) and finally fat deposits in body (still no action)

Drug eliminated from the body at a constant percentage (%) per unit of time

Deltoid area

Absorption through ↑ blood flow in muscle; Irritating drugs may be given via this route; Injection of suspensions

Solutions/suspensions into subcutaneous areolar tissue to circulation. Insulin!

Onset and duration

Phenobarbital stimulates the production of microsomal enzymes that normally metabolize the anticoagulant warfarin

Plasma blood levels equals levels eliminated & proportional to the dose administered

Passive tubular diffusion: Urine pH also plays a role in excretion

If Half-life of a drug is 1 hr; then in __hours drug would be gone; it takes about __ half lives for drug elimination

Alters response of drug, ie. with meal, sedatives before bedtime

Drugs→orally pass through intestinal wall→pass through HEPATIC(liver)portal circulation(metabolize)→inactivate some drug

Excretion can occur through which of the following?

Metabolites are secreted via bile into intestine & continues with some drug being excreted in the cycle→prolonged effect

_____ is the (most common) reactions resulting in the addition of oxygen and/or the removal of hydrogen

______: Reactions resulting in the addition of hydrogen and/or the removal of oxygen

Drugs→Intestine→distribute through serum→pass to specific/non specific sites of action→liver (metabolized)→kidneys

____ transports drug from the bloodstream across the renal tubular epithelial cells into the renal tubular fluid.

First pass effect- (Phase 1 reactions): Lipid molecules are metabolized by?

Renal or hepatic disease complications in metabolism and excretion

______ is the most common; filtered through glomeruli and concentrated in the renal tubular fluid

↑ level of drug in gingival crevices which can aid in periodontal treatment; Tetracycline 4x’s ↑ in GCF than blood level

________ urine: Tubular urine is more _____, weak acids are excreted more rapidly and weak bases excreted more slowly

Phase 1: metabolism bind which to the lipophilic drug?→Result in a modest ↑ in the parent drug's water solubility

Select which of the following is correct in regards to Half-life?

Drugs can be excreted _____ or as metabolites

Herbal, meditation altering physiology of the body (ie. anxiety)

If dosage is increase metabolism rate does not change, therefore duration of drug can be prolonged

Inactive compound→ “prodrug”-metabolizes into an active drug.Disruption in metabolism the harder the action drug to form

Drugs with a high first pass effect have a higher oral-parenteral dose ratio

________- regulates the amount of drug in the tubular fluid

Metabolism (Biotransformation) occurs mostly in the _____

Drugs that cause induction, cause the metabolized drug a increased effect

Depends on amount of plasma protein binding & the glomerular filtration rate

(ie. acyclovir must be absorbed by the cell to form an active metabolite)

Metabolism (Biotransformation): First Pass Effect involves which of the following?

Rate of metabolism remains constant over time, same amount of drug is metabolized per unit of time regardless of dose

(ie. doxycycline active metabolized by liver becomes inactive metabolite)

Zero-order kinetics: Careful change in dosage can lead to unexpected _____

Length of effect

Need for ↑ dosage.Cross-tolerance when a client becomes tolerant to 1 drug, tolerance to other drugs with similar action

Certain populations susceptible to adverse effects, genetic predisposition

Metablosim- (excretion): Excreted through lungs, bile, GI, sweat, saliva, breast milk and the kidneys

↑ ionized, ↓ lipid soluble metabolites hard to absorb in renal cell membranes; retained in tubular fluid/removed via pee

_____ is the reaction with water, a bond in the compound is broken, resulting in two compounds