Week 3 & 4: Anesthetic Pharm

Front 1

Def of Absorption in relation to PharmacoKinetics

Back 1

the transfer of a drug from site of administration to the blood

Front 2

Bioavailability

Back 2

the fraction of the drug that reaches the systemic circulation (100% for IV drugs)

Front 3

Distribution in relation to PharmacoKinetics

Back 3

blood to ECF and/or cells: depends on blood flow, capillary permeability, protein binding, hydrophobicity (lipophilicity) of the drug

Front 4

Volume of Distribution

Back 4

hypothetical vol into which a drug is distributed

Front 5

Protein binding

Back 5

inactive reservior

Front 6

Drug Metabolism in relation to PharmacoKinetics

Back 6

Biotransformation and excretion

Front 7

Polar molecules

Back 7

have an uneven distribution of electrons within the molecule but no net charge

Front 8

Ions

Back 8

molec. with a net elect. charge

Front 9

Rule of solubility

Back 9

"like dissolves like"
so things with a charge will dissolve in other things with a charge or uneven electron distribution

Front 10

Determinants of tissue uptake of drug

Back 10

- blood flow
- concentration gradient
- BBB
- Physiochemical properties of drug: Ionization, Lipid soluble, Protein bound

Front 11

Determinants of capacity of tissue to store drug

Back 11

- solubility
- tissue mass
- binding to macromolecules
- pH

Front 12

Bronsted-Lowry theory of acids and bases

Back 12

an acid donates a H ion
a base accepts a H ion

- an acid-base rxn is one in which a proton is transfered

Front 13

pH

Back 13

a means of expressing H ion concentration

- the pH of environment determines which direction the chemical rxn goes

Front 14

Ka

Back 14

the ionization constant
- the equilibrium constant for the dissociation of acid

Front 15

equation for pH
Henderson-Hasselbach equation

Back 15

pH = pKa + log [A]/[HA]

Front 16

pKa

Back 16

the pH (environment) at which the drug is 50% ionized and 50% nonionized
- has no relation to pH of the drug prep
or the acid/base nature of the drug
- it is an important factor in determining drug onset b/c only the nonionized fraction will readily cross the lipid bilayer

Front 17

ionization constant refers to:

Back 17

the onset of action

Front 18

Ion trapping

Back 18

- only the non-ionized fraction readily crosses the lipid membrane
- once on the other side, the drug may ionize depending on the pH of that new environment
- assume the membrane is the placenta and that there is fetal acidosis

Front 19

are local anesthetics acids or bases

Back 19

bases

Front 20

When the pH is less than pKa what happens

Back 20

the protonated forms HA and BH predominate

Front 21

When the pH is greater than pKa what happens

Back 21

the deprotonated forms A and B predominate

Front 22

there is a more pronounced effect with non-ionized or ionized form

Back 22

non-ionized form has a more pronounced effect of the drug

Front 23

Characteristics of Nonionized drugs

Back 23

- pharmacologically active
- Lipid soluble
- Crosses lipid barrier (GI, BBB, placenta
- Not renal excreted
- Hepatic metabolized

Front 24

Characteristics of Ionized drugs

Back 24

- Pharmacologically inactive
- Soluble in water
- does NOT cross lipid layer (BBB)
- Is renally excreted
- NOT hepatically metabolized

Front 25

Acid Drugs in Anesthesia

Back 25

1. Thiopental
2. Barbiturates
3. Propofol
- weak acids unite with cations (Na)
- Cation of salt of the acid is often named first ex: Sodium pertothal

Front 26

Basic Drugs in Anesthesia

Back 26

1. Local anesthetics
2. Ketamine
3. Benzodiazepines
4. Etomidate
5. Opiods
- weak bases unite with anions (Cl)
- anion named second ex: Morphine Sulfate
- Any drug that is an amine is a BASE

Front 27

Plasma makes up what % of weight fluid and how many Liter

Back 27

6-8%
4L

Front 28

ECF makes up what % of body weight and how many Liters

Back 28

20-23%
14L

Front 29

Total body water is what % of body weight and how many Liters

Back 29

60-64%
42L

Front 30

Physicochemical characteristics influencing Vd:

Back 30

1. Lipid solubility
2. Protein binding
3. Molecular size

Front 31

Distribution by compartment

Back 31

- Plasma: Lrg MW, High protein binding, hydrophilic
- ECF: low MW, hydrophilic (goes through slit jxn)
- Total body water: low MW, lipophilic (hydrophobic)

Front 32

Vd equation

Back 32

Vd = D/C

D = total amount of drug in body (what was given)
C = plasma concentration of drug

Front 33

drug elimination depends on:

Back 33

drug delivered to liver or kidney per unit time

Front 34

delivery of drug to organs depends on

Back 34

blood flow and fraction of the drug in plasma

Front 35

If Vd is Large, most of the drug is where? and is it able to be excreted

Back 35

most of drug is extraplasmic and Not able to reach excretory organs

Front 36

Any factor that increases Vd will increase or decrease half-life?

Back 36

increased Vd will increase half-life and extends the duration of the drug

Front 37

what protein form do Basic drugs bind to?

Back 37

Alpha Acid Glycoprotein

Front 38

First Order Kinetics

Back 38

- Constant FRACTION of available drug metabolized per unit time
- most drugs work this way

Front 39

Zero-Oder Kinetics

Back 39

- Constant AMOUNT of drug is metabolized per unit time
- when plasma concentration of drug exceeds capacity of enzymes

Front 40

Role of Metabolism/Biotransformation

Back 40

Converts active, lipid soluble drug into water soluble drug and pharmacologically inactive metabolites
- if not converted into H2) soluble the drug keeps getting reabsorbed and will not be eliminated

Front 41

Phase 1 of Drug Metabolism

Back 41

1. Oxidation
2. Reduction
3. Hydrolysis
4. Convert lipophilic into polar molec by intro or unmasking a polar fxn'l grp
5. may increase, decrease, or leave unaltered the drug's pharmacologic activity

Front 42

Phase 2 of Drug Metabolism

Back 42

Conjugation: hooked onto drug (usually acid) making cmpd more H2O soluble and therapeutically inactive in Phase 2

Front 43

Consequences of Drug Metabolism

Back 43

1. Accelerated renal excretion
2. Drug inactivation
3. increase therap. action
4. activation of prodrug
5. increase or decrease toxicity

Front 44

What is the most important role in drug Metabolism

Back 44

Accelerated Renal drug Excretion

Front 45

Where are cytochrome P-450 Isoenzymes mainly found?
What are they also known as?

Back 45

in hepatic smooth endoplasmic reticulum (but also found in kidneys, GI tract, and adrenal cortex)

- metabolized in the liver

-aka: Mixed Fxn Oxidase System: b/c they need oxydase and reductase

Front 46

What are the factors that influence the drug to get to a steady state

Back 46

1. Rate of drug infusion: concentration at steady state is DIRECTLY Proportional to infusion rate and INVERSELY Proportional to clearance

2. Time to reach steady state: is INDEPENDENT of rate of infusion

Front 47

Half- Life is INDEPENDENT of?

Back 47

the Amount of drug given with IV injection

Front 48

Steady state is INDEPENDENT of?

Back 48

the Frequency of dosing

Front 49

Distribution is also known as _____ Phase?

Back 49

Alpha phase

Front 50

Elimination is also known as ______ Phase?

Back 50

Beta phase

Front 51

What are the 3 Phases in a 3 Compartment Model

Back 51

1. Rapid Distribution (Alpha Phase)
2. Intermediate (Beta Phase)
3. Slow (Gamma Phase)

Front 52

Describe the Rapid Distribution (Alpha Phase) of a 3 Compartment Model

Back 52

drug from plasma to rapidly equilibrating tissue (VRG, MG)

Front 53

Describe the Intermediate (Beta Phase) of a 3 Compartment Model

Back 53

revered flow btwn plasma and rapidly equilibrating tank secondary to low plasma levels

Front 54

Describe the Slow (Gamma Phase) of a 3 Compartment Model

Back 54

- Elimination Phase
- Terminal Phase
- Drug returns from periphery to plasma
- Rate of elimination is slower than earlier phases d/t low plasma concentrations (first order kinetics)

Front 55

Onset of clinical effect:

Back 55

time needed for the drug to be delivered to the site of action (brain)

- fxn of plasma concentration and the time course of bld brain equilibration

Front 56

Half-Time

Back 56

the time required for half of the drug to be eliminated from the compartment.

Front 57

Context-Sensitive

Back 57

refers to infusion (context means duration)

Front 58

Half-time is DIRECTLY proportional to?

Back 58

Volume of Distribution

Front 59

Half-time is INVERSELY proportional to?

Back 59

CLEARANCE

Front 60

How many half-times does it take for most drugs to be eliminated from the body

Back 60

5-6.5 half-times

Front 61

2 major sites of clearance

Back 61

1. Liver: biotransformation, phase 1&2

2. Kidneys: clearance of unchaged drug in the urine

Front 62

clearance equation:

Back 62

CL = Rate of elimination of drug/ Plasma drug concentration

Front 63

Units of clearance

Back 63

Volume/unit time

Front 64

any factor that increases Vd will do what to half-time

Back 64

Increase half-time

Front 65

Any factor that increases clearance will do what to half-time

Back 65

Decrease half-time

Front 66

Def of PharmacoDynamics

Back 66

the study of the biochemical and physiological effects of drugs and their mechanisms of action

Front 67

Mechanism of Action in reference to PharmacoDynamics

Back 67

most drugs cause their effects by interacting with a macromolecule component (receptor) alerting fxn and initiating a biochem or physiologic change

Front 68

Def or Drug Receptors

Back 68

the component of a cell or organism that interacts with a drug and initiates the chain of biochemical events that leads to the drug's observed effects

- any fxn'l macromolec in a cell to which a drug binds to produce its effects

- Determine the Quantitative Relationship btwn dose and pharmacologic effect

Front 69

Drug receptors are located:

Back 69

1. cell membrane
2. intracellular organelle membrane
3. nucleus

Front 70

Cell membrane embedded enzymes:
Example

Back 70

1. drug binds of surface of cell
2. receptor spans membrane
3. binding causes enzyme activation

Ex. Insulin

Front 71

Ligand-Gated Ion Channels: and Example

Back 71

1. drug binds on surface of cell
2. regulate flow of ion in & out of cell according to concentration gradient
3. specific for individual
4. receptor spans membrane

Ex: Ach and GABA

Front 72

G-Protein-Coupled receptor systems and Examples

Back 72

1. receptor
2. G protein
3. Effector (ion channel or enzyme)

Ex: Norepi, Histamine, Peptide Hormones

Front 73

Transcription factors and Examples

Back 73

1. found within cell on DNA of nucleus
2. stimulates transcription of mRNA molec. and regulates protein synthesis
3. response to activation is delayed

Ex: Thyroid Hormones, Steroid Hormones

Front 74

Isomers vs Racemic mixtures

Back 74

Isomer: only the chemical/drug that causes the desired effect

Racemic: 50:50 mix of enantiomers where one isomer causes the desired effect and the other causes the side-effect

Front 75

High Affinity (Potency)

Back 75

the AMOUNT of drug required to produce a particular effect.

- can bind to receptor even when present in low concentration

Front 76

Intrinsic Activity (Efficacy)

Back 76

the MAX EFFECT that can be produced by a drug. This is independent of dose

Front 77

Substances that work on Ligand-Gated Channels

Back 77

1. Acetylcholine: Nicotinic
2. GABA
3. Excitatory amino acids: Glutamate, Glycine

Front 78

Agonists:

Back 78

bind to & activate receptor causing effect

Front 79

Antagonists

Back 79

bind to receptor preventing binding vy agonist

Front 80

partial agonist

Back 80

bind to receptor but don't evoke as strong response

Front 81

duration of drug action

Back 81

- dissociation from receptor terminates effect
- effect may be prolonged after dissociation if coupling molec. is still present and activated
- drug covalently bonded to receptor may require synthesis of new receptor for termination of action

Front 82

Competitive antagonist

Back 82

interacts with receptors at same site as agonist
- shifts curve to Right so drug appears less potent

Front 83

Non-competative antagonist

Back 83

prevents binding of agonist or activation of receptor
- decreases max response or the drug

Front 84

Partial agonist

Back 84

blocks binding site but less response than full agonist

Front 85

Sensitization

Back 85

Continuous activation or inhibition of receptors can cause physiologic changes

Front 86

UP-Regulation

Back 86

- An INCREASE in the number (density) of receptors as a result of drug induced receptor antagonism
-Ex: Beta blocker: abrupt withdrawal of the antagonist results in exaggerated response to receptor agonist

Front 87

DOWN-Regulation

Back 87

- DECREASE in the number (density) of receptors in response to excess circulating ligand (neurotransmitters)
- Ex: Beta agonist, pheochromocytoma

Front 88

Pharmacokinetic interactions with drug-drug interactions

Back 88

altered absorption, distribution, biotransformation, renal excretion

Front 89

Pharmacodynamic interactions with drug-drug interactions

Back 89

- 2 drugs acting at the same receptor (usually inhibitory): Propofol & Benzo
- 2 drugs acting at different sites (potentiative or inhibitory): Benzo & Opiod

Front 90

Therapeutic Index

Back 90

the difference between the dose of the drug producing the desired effect and the dose producing the undesirable effect
- LD50/ED50

Front 91

Anaphylaxis

Back 91

- form of distributive shock caused by an acute immunologic response the result of an immediate type 1 hypersensitivity rxn
-Mediated by IgE
- severe rxn
- sudden onset
- mortality rate 3.5-10%
- Classification types 1-4

Front 92

Anaphylactoid

Back 92

- clinical presentation like anaphylaxis but it is NOT immunologic
it is chemically mediated

Front 93

2 phases of anaphylaxis

Back 93

1. Sensitization Phase
2. Elicitation Phase

Front 94

Sensitization Phase

Back 94

- Antigen triggers B-cells production of IgE
- Antibodies bind to receptors on the surface of effector cells (mast cells and basophils)

Front 95

Elicitation Phase

Back 95

- Reintroduction of antigen causes activation of effector cells and histamine release
- Clinical presentation is immediate hypersensitivity

Front 96

Risk factors for Anaphylaxis

Back 96

1. hx of drug allergy
2. gender
3. age
4. atopy
5. Latex

Front 97

Atopy

Back 97

may be a risk factor for histamine release in the presence of histamine releasing drugs b/c basophils of atopic individuals more readily release histamine

Front 98

People susceptible to Latex Allergy

Back 98

1. Spina Bifida
2. Healthcare workers
3. Allergy to avocado, kiwi, banana, fig, chestnut, hazelnut, sweet pepper, melon, pineapple, and papaya
4. Eczema, asthma

Front 99

which gender and age group are more susceptible to anaphylaxis

Back 99

Women>men

peak = 4th-5th decade of life (but occurs across lifespan)

Front 100

Pharmacologic agents most common with Anaphylaxis

Back 100

1. NDMR (quaternary ammonium ion is the antigen)
2. Latex
3. Antibiotics
4. Hypnotics (propofol)
5. Colloids (hetastarch)
6. Opiods (Morphine, Demerol release histamine)
7. Local anesthetics (esters)

Front 101

Hallmark of Anaphylaxis

Back 101

Hypotension

Front 102

Presenting symptoms of anaphylaxis under anesthesia: %
1. Cardiovascular:
2. Cutaneous symptoms:
3. Bronchospasms:

Back 102

1. 74%
2. 70%
3. 44%

Front 103

Treatment for Anaphylaxis

Back 103

Primary:
1. Discontinue drug
2. 100% O2
3. Epi
4. consider Intubate or trach
5. IV fluid (1-4L)

Secondary tx:
1. Benadryl
2. Steroid (Hydrocortisone)