Pharmacotherapy II

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug (absorption, distribution, metabolism, excretion)

Question 2

Pharmacodynamics

Answer 2

What the drug does to the body

Question 3

Therapeutic window

Answer 3

Range of blood drug concentration that yields a sufficient therapeutic response (without a toxic reaction)

Question 4

Absorption

Answer 4

How administered drugs are absorbed into body (depends on route of administration)
Many factors including route of admin and bioavailability

Question 5

Distribution

Answer 5

How drugs are distributed to the site of action

Question 6

Metabolism

Answer 6

Biotransformation of the drug from active to inactive form (to prepare for elimination)

Question 7

Bioavailability

Answer 7

Rate and extent a drug is absorbed from a substance (tablet, capsule, etc.) and is available at site of action

Fraction or percentage of an administered dose of drug that reaches the circulation in its unmetabolized form)

First pass effect (hepatic metabolism)
Pro-drugs (active metabolites)
Drug formulation (immediate release vs. extended release)
GI motility
Blood flow

Blood flow and ability of drug to pass through membranes or barriers in the body affect bioavailability, but may also be discussed in the distribution phase of pharmacokinetics

Question 8

First pass effect

Answer 8

Drugs are metabolized by liver before passing into circulation

After absorption into alimentary canal, drugs go directly to the liver through the portal vein

Hepatic enzymes metabolize the drug, reducing the amount of active drug in the bloodstream

Drugs administered orally are subject to the first pass effect

Question 9

Pro-Drugs

Answer 9

Drugs that have no biologic activity itself, but once metabolized in the liver it becomes an active metabolite

Question 10

Immediate release

Answer 10

Delivered to GI tract quickly for quick onset of action
Absorbs well in acidic environment

Question 11

Extended release

Answer 11

Extends activity of drugs in the body to level out high peaks and low troughs of concentrations to achieve a more consistent level in the blood

Question 12

Enteric coating

Answer 12

Slows drug to be dissolved in intestines rather than stomach
Intestines have higher pH
Helps preserve gastric mucosa

Question 13

Gastric emptying

Answer 13

Higher gastric emptying rate hastens absorption and bioavailability in the intestines
High fat meals and solid foods may delay drugs initial delivery to intestinal absorption surfaces

Gastric emptying will contribute to absorption and bioavailability

Question 14

Decreased intestinal motility

Answer 14

Slowed intestinal peristalsis leads to greater absorption and bioavailability

Agents that slow intestinal motility (anticholinergic) will prolong contact time with intestinal surfaces

Question 15

Increased intestinal motility

Answer 15

Increases peristalsis leads to less absorption and bioavailability

Agents which increase motility (laxative) could shorten contact time with intestinal surfaces and therefore decrease drug absorption

Question 16

Blood flow

Answer 16

Absorption and distribution impacted by blood flow based on adequate perfusion

Gut and intestinal perfusion important for absorption

Hypo and hyperperfusion may affect bloodflow and delivery of drug

More vascular areas are better perfused (IM vs. subQ)

Question 17

Absorption routes of administration

Answer 17

Enteral (absorbed through GI tract)

Oral - first past effect

Sublingual, buccal, and rectal bypass the first pass effect and tend to be more potent = quicker onset of action

Question 18

Parenteral

Answer 18

All routes of admin not involving GI tract

IV - rapid access to circulation, immediate serum levels no first pass effect

IM - Slower onset than IV, no first pass effect, absorption required

SubQ - Slower than IM, no first pass effect, absorption required

Question 19

Inhalation

Answer 19

Drug is gaseous or sprayable and delivered directly into lung, no first pass effect, high bioavailability

Question 20

Topical delivery

Answer 20

Applied to skin surface or mucus membrane, local absorption does not cross dermis

Question 21

Transdermal

Answer 21

Systemic delivery of drug through skin over time, intended for steady delivery (nicotine patch)

Question 22

Distribution

Answer 22

Distribution of absorbed drug depends on blood flow to area, lipid or water solubility, and protein binding

Question 23

Protein binding

Answer 23

After absorption, a drug that may circulate through the body unbound (free drug) or bound to carrier proteins. Extent of drug binding to carrier proteins depend on affinity of drug for that protein and concentrations of both drug and protein

Question 24

Lipid and water solubility

Answer 24

How drug gets into cell. Biologic membranes act as barriers, blocking or permitting the passage of various substances

Cell membrane allows most hydrophobic compounds to pass through readily, hydrophilic. substances and ionized substances have a harder time passing through

Question 25

Passive diffusion

Answer 25

Molecules move from one side of barrier to another without expending energy (high to low)

Question 26

Facilitated diffusion

Answer 26

Carrier proteins utilized to transport larger molecules from area of higher concentration to lower

Question 27

Active transport

Answer 27

Requires ATP (energy), molecules may move from lower to higher area of concentration

Question 28

Metabolism

Answer 28

Function of body to change substances into water soluble forms that will more readily be excreted. Beginning of process of elimination Liver primarily performs the metabolic functions of body, kidney and intestines also take part

Question 29

Phase 1 metabolism

Answer 29

Enzymatic process involves oxidation and reduction Drug changed to form a more polar or water soluble compound Hydrolysis

Question 30

Phase 2 metabolism

Answer 30

Involves adding conjugate to parent drug or phase-1 metabolized drug to further increase water solubility

Question 31

Cytochrome P-450 System (CYP450)

Answer 31

CYP composed to superfamilies of more than 100 enzymes Three families (about 15 total enzymes) are responsible for drug metabolism in about 90% of cases Drugs may be a substrate, inducer, or inhibitor of CYP450 system

Question 32

Inducer

Answer 32

Stimulates production of enzymes which increases amount of enzymes available for metabolism (phenytoin, rifampin, St John's Wort)

Question 33

Inhibitor

Answer 33

Inhibits production of CYP enzymes, decreasing metabolism of drugs and increasing circulating levels (grapefruit juice, azoles, protease inhibitors)

Question 34

Elimination/Excretion

Answer 34

Primary route of excretion through kidneys Important to know renal function (GFR) to help dose drugs Other excretory organs (Lower GI tract - feces, lungs - exhalation, and skin - perspiration)

Question 35

Half Life (t 1/2)

Answer 35

Time required for 50% of drug to be eliminated from body If t 1/2 is 10 hours then each 10 hours 50% of what is remaining will be eliminated Drug is considered fully cleared after 4 to 5 half lives of drug Important to consider when prescribing multiple classes of drugs

Question 36

Factors interfering with elimination

Answer 36

Renal failure - increases half life, need to downward dose adjustment Hepatic disease - Impacts pro drugs and CYP450 enzymes, increases half life Exercise regularly vs. intermittently - impacts blood flow, GI motility, body temperature

Question 37

Pharmacodynamics

Answer 37

What the drug does to the body Set of processes that drugs produce specific biochemical or physiologic changes in body Impacted by: - Receptor abundance (age related) - Receptor affinity (age related) - Post receptor changes and sensitivities

Question 38

Agonists

Answer 38

Creates a response Dose dependent Dependent on receptor sensitivity Full agonist: 100% of desired effect Partial agonist creates a partial response

Question 39

Antagonist

Answer 39

Creates no biological response Blocks receptors from agonists Compete for receptor sites Noncompetitive sites

Question 40

Autonomic nervous system

Answer 40

Involuntary functions: Thermoregulation, vascular contractility, heart and respiratory rates, digestion Sympathetic vs. Parasympathetic

Question 41

Somatic nervous system

Answer 41

Voluntary functions, movement, speech

Question 42

Sympathetic

Answer 42

Fight or flight Norepinephrine neurotransmitter Agonist vs. antagonist Alpha1 receptors (smooth muscle effects) Alpha2 receptors (brain, stem, SC, and eye) Beta1 receptors (myocardium) = 1 heart Beta2 receptors (lung) = 2 lungs

Question 43

Parasympathetic

Answer 43

Cholinergic, muscarinic receptors Acetylcholine (ACH) Agonists prolong ACH activity, cause contractions, increased secretions Antagonists = anticholinergics - block the effect of ACH. Urinary retention, xerostomia, increased HR

Question 44

ED50

Answer 44

Drug dose that results in a therapeutic effect of 50% recipients

Question 45

LD50

Answer 45

Drug dose that is lethal of 50% of recipients

Question 46

Potency

Answer 46

Amount of drug needed to produce a response

Question 47

Therapeutic index

Answer 47

TI = (LD50/ED50) If a drug is lethal to 50% at 100mg but effective to 50% of recipients at 25mg TI = 100/25 = 4mg is considered likely a safe dose without side effects If a drug is lethal to 50% of recipients at 50mg but effective to 50% of recipients at 2mg TI = 50/2 = 25mg is considered likely a safe dose without side effects