Lecture 3 Flashcards by Sydney Coopland

ADME

Absorption
Distribution
Metabolism
Excretion

How well did you know this?

Not at all

Perfectly

Study of how a body influences a drug

Pharmacokinetics

How well did you know this?

Not at all

Perfectly

________ is a breakdown of the processes which affect a drug molecule

ADME

How well did you know this?

Not at all

Perfectly

The movement of a drug from the site of administration into the bloodstream
Drugs enter the bloodstream for the purpose of traveling to their target tissues

Absorption

How well did you know this?

Not at all

Perfectly

Administration route
Cell membrane permeability
Drug formulation
Physiology: gastric emptying, surface area, temperature

Factors that affect Absorption

How well did you know this?

Not at all

Perfectly

non-invasive, good for repeated dosing, safety
Subject to first-pass metabolism
Prodrugs

Absorption: ORAL ROUTE

How well did you know this?

Not at all

Perfectly

Intravenous: rapid
Subcutaneous: slower
Intramuscular: larger volumes, slow-release formulas

Routes: Parenteral Routes

How well did you know this?

Not at all

Perfectly

Localized
Mucous membranes? Rapid uptake

Routes: Topical

How well did you know this?

Not at all

Perfectly

Sustained release
Can be irritating

Routes: Transdermal

How well did you know this?

Not at all

Perfectly

Rapid, efficient
Initial localization to pulmonary system

Routes: Inhaled

How well did you know this?

Not at all

Perfectly

When it goes into the stomach first and then the liver it’s called

First pass

How well did you know this?

Not at all

Perfectly

How much of the drug gets absorbed
Usually described as a percentage
Oral? IV?

Bioavailability

How well did you know this?

Not at all

Perfectly

Two drugs that have the same bioavailability and same concentration of active ingredient

Bioequivalents (generic vs brand)

How well did you know this?

Not at all

Perfectly

Drug molecules can cross a barrier passively or actively
Active transport
Passive diffusion

Movement across membranes

How well did you know this?

Not at all

Perfectly

molecule size
lipophinicity
drug ionization

Membrane permeability

How well did you know this?

Not at all

Perfectly

Smaller drugs are absorbed faster than larger drugs

Molecule size

How well did you know this?

Not at all

Perfectly

Lipophilic = increased absorption

Lipophilicity

How well did you know this?

Not at all

Perfectly

Want drugs to be neutral when they are absorbed, not ionized
A basic drug in an acidic environment will not absorb well
An acidic drug in a basic environment will not absorb well

Drug ionization

How well did you know this?

Not at all

Perfectly

Drugs are designed and formulated with the pH of the enteral environment in mind
Weakly acidic drugs are meant to be absorbed in the stomach
Likewise, weakly basic drugs are meant to be absorbed in the intestine (alkaline environment)
Think: neutral is better than ionized, and the pH of the environment surrounding the drug molecule impacts it’s charge
How do we know whether a drug is intended for stomach or intestinal absorption?

Ionization

How well did you know this?

Not at all

Perfectly

Coatings
Buffered medications
Hydrogels
Sustained v. controlled release

Absorption: drug formulation

How well did you know this?

Not at all

Perfectly

Enteric coating (“EC”)
Prevents drug from dissolving in stomach
Enteric coated tabs absorb in the intestine
Therefore, we do not EVER crush or dissolve an enteric coated tab prior to administration! (no GT tubes, no pudding)

Coatings

How well did you know this?

Not at all

Perfectly

Drug contains ions to decrease gastric acidity

Buffered Medication

How well did you know this?

Not at all

Perfectly

drug released over period of time

Controlled release

How well did you know this?

Not at all

Perfectly

drug released at a constant rate over time

Sustained release (“SR”)

How well did you know this?

Not at all

Perfectly

high dose intended to release over extended period. Crushing, chewing, splitting or opening immediately releases the entire dose

Extended-release (“XR”) formulations

_________ drugs cannot be administered PO Example: InsulinProtein would be digested by the stomach and rendered useless. That is why we inject insulin.

Protein-based

some drugs may have unpleasant effect on oral cavity (bitter taste, stain teeth, irritate mucosa). Any drug with an oral cavity effect may have a more palatable alternative (e.g: sweetened liquid) so ask pharmacy!

Other considerations for crushing

Gastric emptying Blood flow Surface area Body temperature

Psysiologic and other factors that affect absorpotion

Fatty foods delay emptying Some drugs can decrease motility Nursing implication for this?

Gastric emptying

Increased blood flow = increased absorption

Blood flow

Can affect topicals

Body Temperature

Transport of a drug by the bloodstream to its site of action

Distribution

Blood flow to target tissue Drug solubility (lipophilic/hydophobic) Drug-Protein binding Special physiologic barriers Blood-Brain Barrier Fetal circulation

Factors affecting distribution

More blood flow = more drug reaching target tissue Drugs distribute first to areas with ++ blood supply

Blood Flow to target tissue

Lipid-soluble cross cell membranes more readily Drugs in their active form are usually lipophilic Question for thinking! – equal amounts of lipid-soluble drug and water-soluble drug – which one will have higher plasma concentration?

Solubility

Drugs will bind to proteins in the bloodstream (albumin) Only unbound drug molecules can freely distribute – “active” low albumin levels = risk for toxicity

Drug-protein binding

two medications that are highly protein-bound may “compete” for binding sites on the albumin.

Protein binding site competition

Creates more free, unbound drug = unpredictable drug response This is called a ______ interaction

drug-drug

when the presence of one drug decreases or increases the action of another drug administered concurrently

Drug to Drug Interaction

Does not contain capillary pores Protects brain from pathogens and toxins Only lipid-soluble drugs able to cross Not fully developed in neonates Inflammation can increase permeability

Blood-brain barrier

Prevents harmful substances from passing from mother's blood stream to fetus Permeability of barrier changes during pregnancy However, some drugs can cross (alcohol, cocaine, caffeine, some prescription meds) Pregnancy categories for drugs Must consider if patient is of childbearing age prior to prescribing a drug.

Fetal-placental barrier

Also called Biotransformation

Metabolism

________ alteration of a drug into: Inactive metabolite A more soluble compound A more potent metabolite (conversion from a Prodrug) A less active metabolite

Biochemical

Large class of enzymes, known as microsomal enzymes Targeted against lipophilic medications (most meds)

Hepatic Enzymes: Cytochrome P450 System

Drugs that are metabolic targets of specific enzymes are said to be _______ of those enzymes

substrates

So, lipid-soluble meds are “substrates” of the _____ enzymes

CYP450

Lots of drugs ______ the CYP450 system – results in toxicity Some substances _______ the CYP450 system – “inducers”

inhibit; activate

CYP450 _____ drugs

metabolizes

genetics, presence of other drugs, certain foods

Influence inhibition and induction

Inducer Other inducers: caffeine, chronic alcohol, chronic tobacco

St. John’s Wort (NHP)

Inhibitor

Grapefruit Juice

CYP450 System responsible for _______ effect!

first-pass

__________ affects CYP

Nutritional status

Metabolic pathway competition: 2 drugs competing for the same enzyme? -> another ______________

drug-drug interaction

Structural change = _______ change

functional

Metabolite could be __________ (because metabolism inactivated the drug)

non-functional

Metabolite could be __________ (because the metabolism activated the prodrug)

functional

Codeine is a prodrug for

morphine

Some metabolites are _______ to the liver

toxic

Tylenol metabolites – _______, __________ *when used appropriately – Tylenol has high safety profile!

liver, kidneys

Infants: immature CYP system Elderly: enzyme activity reduced Genetic polymorphisms

Lifespan: metabolism

Elimination of drugs from the body - Kidney - Pulmonary - Glandular - Intestinal/fecal

Excretion

_________ affects blood concentration Inverse -> more excretion = lower blood concentration

Excretion rate

May come to kidney as metabolites, or in active form Metabolized drugs are easier to excrete (due to polarization + water solubility) Passive diffusion in the glomerulus Many drugs stay in the urine and do not get resorbed Changes in urine pH can influence whether a molecule gets reabsorbed Kidney damage = reduced renal excretion -> clinical implication?

Renal excretion

Gases and volatile liquids Most drugs excreted unmetabolized Excretion rate affected by resp rate and blood flow

Pulmonary Excretion

Sweat, saliva, breast milk, seminal fluid Water-soluble molecules

Glandular Excretion

“biliary excretion” Enterohepatic recirculation

Intestinal Excretion

Pharmacotherapy goals Onset of action Duration of action Peak effect Peak level Half-life Steady state

Time-response relationships

Maintain drug at concentration that produces therapeutic response

Pharmacotherapy goals

time required for a drug to elicit therapeutic response

Onset of action

time period during which drug is in therapeutic range

Duration of action

time required to reach maximal therapeutic response Corresponds physiologically to increasing drug concentration at site of action Not to be confused with peak level

Peak effect

_________ = highest blood level; Trough Level = lowest blood level

Peak Level

Time required for serum levels to be reduced by one half (50%) Represents the rate of elimination 5 half-lives to reduce by 97% Clinically useful to determine steady-state, estimates duration of action Shorter half life – given more frequently (morphine half life 3 hrs) Steady State Physiological state in which the amount of drug removed via elimination = the amount of drug absorbed with each dose

Half-life

__________ = consistent levels that correlate with maximum therapeutic benefits Steady state is achieved in about 5 half-lives worth of time for the drug

Steady state

Topical (direct app. to skin) Optic Otic Vaginal Inhaled Nebules Rectal

Medication adminstration

topical administration is often used to produce an effect at the place it is applied Unintended adverse effects usually due to drug being absorbed into circulation

Local effects

some drugs given topically are absorbed into blood to produce effects throughout the body Slow release preparations Consider the pharmacokinetic principle of “Absorption"

Systemic effects

Can be formulated and applied to achieve local or systemic effects Application is directly to the site of intended action Fewer adverse effects than enteral or parenteral routes No first pass metabolism or digestion by liver enzymes For some routes, patient does not have to be conscious

Advantages of Topical

Can be irritating to site of administration Local application can produce systemic adverse effects

Disadvantages of Topical

Sublingual* Buccal* Lotion, ointment, cream, powder, foam, patch, disc Direct application to skin or mucosa Direct application to mucous membrane Inhalation of medicated aerosol spray Inhalation of dry powder medication Inserting medication into a body cavity

“Topical” covers many forms of drug

Cleansed + Dried, hairless Assess prior to application (elderly – thin skin) No open areas (unless specified for wound – sterile technique!)

Skin Prep

Skip prep Use gloves/applicators Thicknss of application

Skin Applications

Lotions + ointments

spread evenly

rub in firmly

Liniment

If applying _______, have pt turn their head to avoid accidental inhalation

powder

a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream.

Transdermal patch

Nasal spray, drop, or tampon

Intransal route

easy, avoid first-pass

Intranasal advantages

Cilia damage, mucosal irritation, absorption may be affected by mucous secretions

Intranasal disadvantages

Spray: tilt head back, to the side being treated Drops: depends on target area Remain in position 5 minutes

Intranasl positioning

Sympathomimetic medications Long-term decongestant use

Intranasal

tilt the head backward

Instilling Nasal Drops: Posterior Pharynx

place head gently over edge of bed OR pillow under shoulders and tilt head back

Nasal drops: Ethmoid or Sphenoid sinus

tilt head back and turn towards the side to be treated

Nasal drops: Frontal or Maxillary

Forms: drops, ointments, Intraocular disc

Opathalmic

Gently roll container Instruct patient to look up Non-dominant hand: use cotton ball, gently pull lower lid open to expose conjunctival sac Dominant hand: rest on patient forehead, hold dropper 1-2 cm above conjunctival sac Do not touch dropper to the eye Do not touch dropper with your fingers Never apply gtts to the cornea; drops should go into the conjunctival sac If you miss (patient moved or blinks), repeat procedure Drops before ointment

Instilling drops

Lecture 3 Flashcards

(98 cards)