Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathophysiology/Pharmacology > Chapter 3 - Pharmacokinetics and Pharmacodynamics Adverse Drug Reactions > Flashcards

Chapter 3 - Pharmacokinetics and Pharmacodynamics Adverse Drug Reactions Flashcards

1
Q

Pharmacokinetics

A
  • The study of drug movement throughout the body
  • Focuses on what the body does to drugs after they are administered.
    • Pharmaco means “medicines”
    • Kinetics means “movement”

To produce a therapeutic effect a drug must reach its target cells in sufficient quantities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Drug Barriers

A
  • For most drugs the process to reach target cells to cause a physiological change is challenging.
  • Exposed to barriers:
    • Crossing membranes
    • Ex. Drug taken by mouth must cross plasma membranes of the mucosal cells on the GI tract and endothelial cells of the capillaries to enter bloodstream
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Drug Barriers: Physiological

A
  • By mouth: stomach acid and digestive enzymes break down drug molecule
  • If seen as a foreign body phagocytes may attempt to remove drug or immune system will be triggered
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pharmakinetic Processes

A

4 categories

  1. Absorption
  2. Distribution
  3. Metabolism
  4. Excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Crossing Plasma Membrane

A
  • Almost always drugs must cross a plasma membrane to enter target cells and produce effects.
  • Plamsa membranes - composed of lipid bilayer, with proteins and other molecules
  • Cross membranes with:
    • Diffusion
    • Active transport
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Factors affecting movement across plasma membranes

A

Passage across a plasma membrane using diffusion dependent on the physical characteristics of the molecule.

Drugs that are small, nonionized, and lipid soluble will pass through easier.

  1. Size of drug molecule - smaller past through membranes easier
  2. Ionization of molecule - environmental pH effects absorption
  3. Lipid solubility - highly lipid-soluble drugs absorbed more rapidly than low lipid-soluble drugs

Drugs may also enter through open channels is the plasma membrane but must be very small.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Diffusion

A
  • Passive transport
  • Movement of a checmical from and area of high concentrtion to low
  • Asssumes that the chemical is able to freely cross the plasma membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Facilitated diffision

A
  • Spontaneous passive transport
  • Utilizes membrane carrier proteins to cross membranes
  • Along with concentration gradient
    Requires no energy but target carrier proteins should be present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Active transport

A
  • Requires cell energy acquired through breakdown of glucose. Adenosine triphosphate (ATP) is produced to release energy
  • Utilizes carrier proteins (also called pumps) in active transport to cross membranes
  • Against a concentration gradient
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Absorption

A
  • Process of moving a drug from the site of administration to the bloodstream.
  • Primary factor for determining onset of drug action
    • The more rapid the absorption the faster the onset
  • Determnes intensity of drug with high absorption leading to a more effective response
  • Ensure client is compliant with medications and completes entire recommend course of Rx
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Route of administration

A

One of the most important variables affecting absorption

3 broad categories of routes:

  • Enteral
    • Enteric-coated
    • Extended release
    • Oral transmucosa, sublingual and buccal
  • Topical
  • Parenteral
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Route of administration: Enteral

A
  • Drugs delivered to GI tract delivered orally (PO) or via nasogastric (NG) or gastrostomy tubes
  • Most intended for absortop to general circulation
  • Tablets and capsules most common
  • Must dissolve before drug available for absorption
  • Slow onset time
  • Oral liquid absorbed faster as there is not wait for tablet to dissolve
  • Tablet may have protective coating against stomach acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Enteric: Enteric coated tablets

A
  • Hard-waxy coating designed with a coating to resist stomach acid
  • Designed to dissolve in the alkaline environment of the small intestine
  • May have because drug has contents that could irritate the stomach
  • In cases of overdose the slow absorption of the tablet allows for retrieving medication through vomiting it suction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Enteric: Extended release (XR, XL)

A
  • Tablets designed to dissolve slowly, resulting in longer duration of action
  • Also called:
    • Long-acting (LA)
    • Sustained release (SR)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Chewing or crushing tablets

A

Not unless the manufacturer specifically states that this is permissible

  • NEVER:
    • Extended reales formulas - high dose intended to be release over time
    • Enteric-coated drugs - exposes drugs to stomach acid
    • Oral cavity drugs - if covered in sweet layer the better taste of a drug will be exposed or they could stain teeth, irriate mucosa, cause an anesthetic effect

As an alternative to crushing liquid forms such as elixirs, syrups or suspensions can assist.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

First pass effect

A

Drugs absorbed from the stomach and small intestine travel to liver, where they may be inactivated before reaching target organ(s)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Enteric: Oral transmucosal / Sublingual and buccal

A

The mucosa of the oral cavity contains extensive capillaries that provide an excellent absorption surface.

  • Medications kept in mouth
  • Not subjected to stomach acid, no first-pass effect
  • Sublungual - under tongue - rapid onset
    • If multiple medications ordered, administer oral medications first, then sublingual preparations.
  • Buccal - place medications in cheek - thicker membrane slower absorption than sublingual
    • Buscal speferred for sustained release
    • Not subjected to stomach acid, no first-pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Enteral: Nasogastric (NG) and gastrostomy (G) tubes

A
  • Medications administered through devices
  • Usually liquid form
  • Solid drugs that are crushed tend to clog tubes
  • Do not use enteric coated or sustained-release medications
  • Drugs exposed to same processes as those given PO
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Topical

A

Applied to skin, mucous membranes (eye,ear, nose, respiratory tract, urinary tract, vagina rectum)

  • Skin most common
  • Assess skin for rash, sores prior to administering med
  • Skin has slow absorption, thin mucous membranes are faster
  • Fewer adverse effects than PO as effect is localized and the amount reaching the bloodstream is minimal
  • Some given for slow release, which are give for their systemic effects rather than localized
    • Ex. Nitroglycerin patch for coronary artery disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Topical: Transdermal patches

A
  • Effective means of delivering certain medications
  • Ex. Nitroglycerin for angina pectoris
  • Provide a apecified amount of medication
    • Rate of delivery can vary
    • Dose vary
    • Patches changed on a regular schedule such as daily or weekly
  • Avoid first pass effect and btpass digestiveenzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Topical Routes

A
  • Ophthalmic route - eye
    • Local conditions of eye, surrounding structures
  • Otic route - ear
    • Medications should be at room temperature.
  • Intranasal route
    • Excellent surface for drug delivery but mucus secretion unpredictable
    • Well vascularized
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Topical Routes

A
  • Vaginal route
    • Local conditions or birth control
  • Rectal route
    • Local or systemic
    • Safe, effective for comatose patients
    • Suppository or enema
    • Drugs administered into the superior aspect of the rectum are susceptible to hepatic first pass, whereas drugs administered lower into the rectum initially bypass the liver.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Parental Route

A

Administration of drugs by routes other than enteral or topical.

  • A needle is used to deliver drugs into skin, subcutaneous tissue, muscles or veins.
  • Less common: intra-arterial, interosseous, body cavities (intrathecal), or organs
  • More invasive
24
Q

Intradermal and Subcutaneous

A
  • Injection into the skin delivers drug to the blood vessels that supply the various layers of skin
  • Intradermal or subcutaneous
    • Major difference is depth of injection
    • Subcutaneous route delivers drugs to deepest layers of skin - Insulin, heparin, vitamins, vaccines
  • Avoids digestive enzymes and first-pass effects
  • Small vollue injections
    • ID: .1-.2 mL
    • Sub: .5-1 mL
25
Q

Parental: Intramuscular (IM)

A
  • Drugs directly into large muscles
  • Muscle tissues has a rich blood supply - drug onset more rapid than oral, ID, or subcutaneous
  • Tissue can receive larger volume of drug
    • Adults with well developed muscles can tolerate up to 3 mL in gluteus Maximus and medius
    • Deltoid .5-1 mL
26
Q

Parental: Intavenous (IV)

A
  • Delivers drugs and fluids directy to the bloodstream
  • Fastest onset but also most dangerous
  • Avoids digestive enzymes and first pass effect bolus
  • 3 basic types
    • Large-volume infusion
    • Intermittent infusion
    • IV
27
Q

Factors Affecting Absoprption: Drug Concentration and Dose

A
  • Higher dose produces a faster, greater response for most drugs
  • higher dose produces a greater concentration gradiet for diffusion and more of the drug wil be absored and reach target cells
  • Drugs primarily absorbed by passive or active transport
28
Q

Factors Affecting Absoprption: GI tract environment

A
  • Oral drugs use passive transport to move from higher concentration of GI tract to lower concentration in bloodstream
  • Most absorption occurs in small intestine - longest with absorptive surfaces of the microvilli
  • Digestive motility is variable among patients
  • Presence of food (high fat/solids) in stomach slows absorption
29
Q

Factors Affecting Absoprption: Blood Flow to the Absorption Site

A
  • Drugs absorbed faster from body areas with high blood flow
  • Diminished blood flow during heart failure or shock
  • Blood flow can purposely be manipulated to slow absorption - vasoconstrictors and Ice packs
30
Q

Factors Affecting Absoprption: Drug Ionization

A

Ionized molecules are those that carry a positive or a negative charge.

Most drugs can exits in a changed or unchanged state depending on pH of surrounding fluid

The ionization of the drug effects its ability to cross plasma membranes

  • Acids are absorbed in acids because they are non-ionized
  • Bases are absorbed in bases because they are non-ionized
31
Q

Factors affecting Absorption: Drug Interactions

A
  • Drug–drug and food–drug
  • Can affect absorption
  • High-fat meals slow stomach motility
32
Q

Factors Affecting Absorption: Surface Area

A

Drugs absorbed faster when applied to regions with a larger surface area such as small intestine, lung

33
Q

Distribution

A
  • Decribes movement of medications throughout the body after absorption
  • Process of drug delivery to body tissues/fluid
  • Depends on blood flow to tissues, drug solubility, protein binding, and some special barriers to block drug distribution
34
Q

Factor Affecting Distributuon: Blood Flow

A
  • Simplest factor is the amount of bloos flow to body tissue
  • Drugs quickly distributed to organs with large blood supply such as heart, liver, kidneys.
  • Slower distribution occurs to internal organs, skin, fat and muscles
35
Q

Factor Affecting Distributuon: Drug Solubility

A
  • The physical properties of a drug greatly influence how it moves throughout the body
  • Lipid-soluble drugs easily cross cell membranes and blood-brain barrier: Lipid-soluble drugs more completely distributed
  • Water soluble drugs can’t easily cross cell membranes or blood-brain barrier
36
Q

Factor Affecting Distributuon: Tissue Storage

A
  • Some tissue has the ability to accumulate and store drugs in high concentrations
  • Bone marrow, teeth, eyes and adipose tissue have an especially high affinity or attraction for certain medications
  • Drugs may remain in body and released very slowly back into circulation
37
Q

Factor Affecting Distributuon: Drug-protein binding

A
  • Many drugs bind reversibly to plasma proteins, particularly albumin to form drug-protein compexes
  • Too large to cross the membrane
    • Drug continue circulating and are unavailable for distribution to the site of action
  • Only free, or unbound protein can reach target cells
  • Number of binding sites on protein limited
    • When two or more drugs compete for the same binding site the drug with greatest affinity binds first
    • May result in a displaced medication reaching high levels producing adverse effects
38
Q

Factor Affecting Distributuon: Special barriers to drug distribution

A

Most capillaries are pourous as they have spaces between endothelial cells and drugs can exit blood stream through these.

The brain and placenta have special barriers.

  • Fetal–placental barrier
    • Prevents harmful substances from passing from mother’s blood stream to fetus
    • Inefficient: Substances such as alcohol, cocaine, caffeine, prescriptions can easily cross
    • No prescription, OTC, herbal therapy should be taken without consultation
  • Blood-brain barrier (BBB)
    • Endothelial cells sealed by tight junction and thick membrane
    • Purpose: protect brain from pathogens and toxins
    • Permits highly lipid soluble drugs, such as general anesthetics, sedatives, antianxiety drugs, anticonvulsant drugs
    • Not allow to enter for antitumor and antibiotic drugs
39
Q

Factors Affecting Distribution: Metabolism

A

Or biotransformation is the process used by the body to chemically change a drug molecule.

  • Metabolism - process that changes activity of a drug and makes it more likely to be excreted
  • Alters structure and function of drug molecules, nutrients, vitamins, and minerals
  • Primary site is liver – reduce dose if liver disease
  • Metabolic reactions change the drug structure to allow for excretion
  • Functional changes alter pharmacological activity providing an essential detoxifying effect
  • Metabolites (results of metabolism) usually have less pharmacological activity
  • Some cases may be greater:
    • e.g., 10% of codeine converted to to morphine
    • May be more toxic (e.g., Acetaminophen - converted to a metabolite that is highly toxic to liver)

In a few cases a drug has no pharmacological activity until metabolism - prodrugs

40
Q

Prodrugs

A
  • A drug that has no pharmacological activity until it under goes metabolism
  • Often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract.
41
Q

Hepatic microsomal enzymes

A

Metabolism in the liver is accomplished by the hepatic microsomal enzyme system

Enzyme complex known as the CYP450 enzyme system named after:

  • Cytochrome P450 (CYP450)
    • An enzyme that metabolizes many drugs, nutrients and endogenous substances
  • CYP450 and more than 50 isozymes - group of enzymes that catalyze the same reaction
  • Each isozyme performs slightly different metabolic functions.
    • Determine speed at which drug is metabolized
    • Contribute largely to drug‒drug interactions
42
Q

Drug roles during metabolism

A

There are 3 major concequenses of the CYP450 system.

  • Drugs as substrates of CYP450
    • When drugs are metabolized by a CYP450
  • Drugs as enzyme inhibitors
    • Some drugs able to inhibit action of CYP450 isozymes
    • May be specific to one CYP450 enzyme or all
    • Could effect metabolism and prolong drug effect or create toxicity
  • Drugs as enzyme inducers
    • Some increase metabolic activity in the liver - enzyme induction
    • Drug level may decrease more rapidly
43
Q

Factor affecting Metabolism

A

The baseline level of hepatic micropsomal enzyme function is genetically determined.

  • Age
    • Infants lack mature microsomal enzyme systems, limits ability to metabolize drugs
    • Older adults require smaller doses of medication: Enzyme activity often reduced in older adults
  • Drug-enzyme reaction
    • Increase in some medication-metabolizing enzymes requiring increased dose to maintain therapeutic level
  • drug-drug reaction
    • Drugs competing for similar pathways decreases rate of metabolism of medication, leading to medication accumulation
  • First-pass effect - the liver increases the rate of metabolism of a medication by inactivating the medications on their first pass through the liver
    • Non-enteral route (sublingual, IV) avoids high first-pass effect
  • Liver impairment and Heart Failure can lead to decreased metabolism
  • Malnutrition can lead to deficiency in factors needed to produce specific medication-metabolizing enzymes, thus impairing medication metabolism
  • Genetic variations of CYP enzymes
44
Q

Excretion

A

Process remove drugs from the body

Drugs will continue to act on the body until they are either metabolized or excreted.

  • Rate of excretion determines drug blood level - duration of action
  • Liver or kidney disease can elongate duration and intensity
45
Q
A

The baseline level of hepatic micropsomal enzyme function is genetically determined.

  • Age
    • Infants lack mature microsomal enzyme systems, limits ability to metabolize drugs
    • Older adults require smaller doses of medication: Enzyme activity often reduced in older adults
  • Drug-enzyme reaction
    • Increase in some medication-metabolizing enzymes requiring increased dose to maintain therapeutic level
  • drug-drug reaction
    • Drugs competing for similar pathways decreases rate of metabolism of medication, leading to medication accumulation
  • First-pass effect - the liver increases the rate of metabolism of a medication by inactivating the medications on their first pass through the liver
    • Non-enteral route (sublingual, IV) avoids high first-pass effect
  • Liver impairment and Heart Failure can lead to decreased metabolism
  • Malnutrition can lead to deficiency in factors needed to produce specific medication-metabolizing enzymes, thus impairing medication metabolism
  • Genetic variations of CYP enzymes
46
Q

Excretion: Renal

A

Renal excretion

  • Primary site of excretion is the kidney
  • On an average person the kidneys filter apx. 180 L of blood each day.
  • Unbound (free) drugs, water soluble agnets, electrolytes, and small molecules pass through pores of glomerulus and enter filtrate in the renal tubule
  • Proteins, blood cells, and drug-protein complexes are not filtered because of large size
  • After filtration may undergo reabsorption to return to circulation. Iolized and water soluble drugs generally remain in filtrate
  • Drug-protein complexes and other substances too large to enter filtrate sometimes secreted into the distal tube of the nephron
  • Secretion mechanism less active in infants and enderly
  • Dose reduction indicated in renal impairment
  • Renal excretion dependent on the pH of the filtrate in the renal tubule
    • Acids excreted more efficiently when the filtrate is slightly alkaline
    • Bases excreted more efficiently when the filtrate is slightly acidic
  • Can manipulate kidney filtrate pH to help excrete toxins
47
Q

Excretion: Pulmonary

A

Drugs delivered by gas or volatile liquids (vaporize at room temp)

  • Rate dependent on factors that affect gas exchange including diffusion, gas solubility and blood flow
  • Dependent on respiratory activity: the faster the breathing rate, the more rapid excretion
  • Lungs ecrete most drugs in their original unmetablized form
48
Q

Excretion: Glandular secretion

A

Water-soluble drugs may be secreted into the saliva, sweat or breast milk

49
Q

Excretion: Fecal and biliary

A

Certain oral drugs travel through the GI tract without being absorbed and are excreted in the feces

  • Biliary secretion - Some secreted as bile. Enter the duodenum and eventually leave the body in the feces
  • Enteroheptic recurculation - Some substances in bile are reabsorbed and circulated back to the liver. This allows for salvaging and reusing useful substances
  • May recirculate numerous times with the bile extending their half-life in the body possibly prolonging drug action.
    • Eventually metabolized by the liver and excreted by the kidneys
50
Q

Time‒Response Relationships

A

Therapeutic response - depends on plasma concentration of most drugs

  • Therapeutic drug monitoring - common practise to monitor the plasma levels of drugs that have a low safety margin to predict drug action or toxicity
    • Used by health care providers to keep drug dose within predetermined range
  • Minimum effective concentration (MEC) - amount of drug needed to produce therapeutic effect (drug potency)
  • Therapeutic rage - range at which drug produces desired action
  • Toxic concentration - level of drug that results in serious adverse effects
  • Therapeutic Index (TI) - quantitative measurement of the safety of a drug. high TI has wide safety margin; low TI requires careful monitoring of serum levels (vancomycin trough levels)

Nurse’s goal is to keep plasma concentration in the therapeutic range.

51
Q

Duration of action

A
  • Length of time a drug concentraion remains in therapeutic range
  • Determined by how rapidly the drug is metabolized and excreted
  • Most common description used is plama half life (t1/2) - the length of time required for the plasma concentration of the drug to decrease by one half after administration
52
Q

Time‒Response Relationships: Drug half-life

A

How long it takes a drug to be 50% less active or eliminated

  • Half-life estimates duration of action for most medications
  • A drug takes apx. 4 half lives before the agent is functionally eliminated
  • Usually takes four half-lives to achieve steady state; longer in long half-life drugs
  • Half-life effected by person specific metabolism as well as liver and kidney function
  • Mode of administration also effects half life – IN and IV will decrease ½ life
53
Q

Drug half-life - estimate of duration of action

A
  • Plasma half-life (t1/2) - Plasma concentration decreases ½
  • Short half-life - Drug given more frequently (4-8hr)
  • Long half-life - Drug given less frequently (24hr, HR toxicity).
  • Takes approximately four ½ lives until drug is excreted
54
Q

Repeated dosing

A
  • Few drugs are admininisterd as a single dose. When multiple doses given the goal is to keep the drug plasma level continuously within the therapeutic range.
  • Results in accumulation of drug in the blood stream.
  • Goal is to reach a plateau drug plasma level and maintain it - amount of drug excreted is the amount absorbed
    • Theoretically, it takes apx. 4 half lives to reach
    • If medication given as a continuously infusion the plateau can be reached and maintained without fluctuation in drug plasma levels
    • Plasma drug levels not smooth, they are peaks and troughs
      • Sustained release have minimized peaks and troughs

Platea may be reached faster by administration of loading doses followed by regular maintenance doses.

55
Q

Repeated dosing: Loading and Maintenance dose

A

The plateau may be reached faster by administration of loading doses followed by regular maintenance doses.

  • Loading - higher amount of drug given once or twice to “prime” the bloodstream with a level sufficient to quickly induce therapeutic response.
    • Particularly important for drugs with long half life
    • Critical to raise drug levels quickly
  • Maintenance dose - keeps concentration in therapeutic range or “steady state”

Pathophysiology/Pharmacology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions