Pharmacokinetucs 1

Question 1

What are the two primary routes of drug administration

Answer 1

Alimentary Canal - Enteral administration

Non-alimentary routes - parenteral administration (not using digestive system, going directly into body)

Question 2

Adv. of Parenteral

Answer 2

Parenteral
- more predictable quantity of drug
- more directly to target site
- usually noy subject to frist pass in liver

Question 3

Oral Admin

Answer 3

• most common
• easiest
• avoids large sudden increases in plasma levels
• large SA of microvilli for absorption
• drugs have to be highly lipid soluble (or in a lipid capsule)
• may irritate the stomach
• acid environment may damage the drug before reaching target tissue
• first pass effect
• amount an rate that reaches blood is less predictable (then injection)
• factors affecting intestinal absorption can impact manner the drug is absorbed (food, infection)

Question 4

What is the first-pass affect

Answer 4

When drugs are administered orally, after being absorbed in alimentary canal, they go to liver via the portal vain where the drug is metabolized and destroyed prior to reaching site of action. dosage must be high enough to survive hepatic degradation

Question 5

Sublingual and Buccal

Answer 5

• undertounge or in cheek
• absorbed through oral mucosa into venous system and straight to heart SO they dont pass through liver and can avoid first pass
• faster effects
• must be able to pass eaily through oral mucosa
• amount that go is limited

Question 6

Rectal

Answer 6

• absorbed poorly or incompletely
• irritation of tissue
• adv. for unconscious patients or those who are throwing up
• only for local conditions like hemorrhoids

Question 7

Inhalation

Answer 7

• pulmonary admin is advantageous bc large SA (alveolar) for diff
• rapid entry into bloodstream

-anesthesia

• could irritate the respiratory tract
• drug particles could be trapped my mucus and cilia
• • hard to tell how much really reaches respiratory tract

Question 8

Injection (list the 4)

Answer 8

• systematically or locally
• must be sterilized or infection
• IV; hits peak levels almost instantly and reach target site fast, allows prolonged and steady infusion, exact amount into blood
• Intra-arterial; directly into artery, difficult and dangerous, used in chemo for minimal exposure to healthy tissue, radiopaque dies for diagnostic procedures
• Subcutaneous; injecting meds directly beneath skin, used fro local responses (local anesthesia), slower more prolonged release, insulin injection, hormonal contraceptives, can deliver only small amount of drugs
• Intramuscular; accessible, botulinum into hyperexcitable muscles for spasms, steady prolonged release without spikes in blood levels like IV, rapid effects, local pain/soreness
• intrathecal; into shealth such as spinal subarachnoid space for narcotic and local anesthetics, bypass BBB into CNS, inflammation treatment

Question 9

Topical Meds

Answer 9

• directly to skin
• often to treat conditions on skin b they’re absorbed poorly into epidermis and circulation
• eye drops and ear drops
• to mucous membranes (nasal mucosa w nasal spray)

Question 10

Transdermal

Answer 10

• applied to skin surface with the intent that they will be absorbed through dermal layers to subcutaneous tissue or peripheral circulation
• must be able to penetrate skin and avoid degradation by metabolizing enzymes in local dermis
• slow controlled release, constant plasma levels
• medicated patches
• iontophoresis and phonophoresis

Question 11

iontophoresis and phonophoresis

Answer 11

iontophoresis; an electric current drives the ionized form of the medication through the skin

phonophoresis (sono); uses ultrasound waves to enhance transmission of the medicaiton through dermis

Question 12

Bioavailability

Answer 12

the percentage of the drug administered that reaches the bloodstream

(if 100mg of a drug was administered by an IV, 100% would be available in the blood stream)

depends on route administered and membrane solubility

Question 13

Dynamic Ion channels

Answer 13

Many drugs can affect their ability to open and close to alter cell excitability

Question 14

What are the different methods of passing through a cell membrane

Answer 14

passive diffusion
active transport
facilitated diffusion
endocytosis

Question 15

Passive Diffusion

Answer 15

• there must be some kind of gradient (like concentration, electrical or pressure
• rate depends on the magnitude of the gradient, size of substances, distance its going and temp
• membrane must be permeable to diffusing substance
• many drugs are lipid-soluble
• some non-lipidsoluble substances (proteins) can be encapsulated in lipid vesicles

Question 16

What affect does ionization have on passive diffusion?

Answer 16

• drugs will diffuse more readily through the lipid layer if they are in their neutral. nonionized form, ionization decreases their lipid solubility
• most drugs are weak bases or acids
• when a weak acid drug is in an acid environment (like stomach), it tends to be in its neutral form and can be absorbed into blood easily
• a weak base is ionized in an acidic environment and poorly absorbed until it reaches duodenum where it becomes nonionized and can go into blood

Question 17

What is diffusion trapping? Where does it occur?

Answer 17

• nephron of kidney
• better for drug to be IONIZED here so it is excreted, if its nonionized it may be reabsorbed back into blood
• if urine is basic, weak acid drugs are trapped and excreted
• if urine is acidic, weak bases are trapped and excreted

Question 18

Diffusion between cell Junctions

Answer 18

primary way a drug can pass through is diffusing into one cell and out the other side (not between cells)

Question 19

Active Transport

Answer 19

• uses membrane proteins to carry substances across cell membranes
• carrier specific
• expenditure of energy (ATP hydrolysis)
• can transport against concentration gradient
• protein pump

Question 20

Facilitated diffusion

Answer 20

• assisting protein carrier is present, but no net energy is expended (features of active and passive transports)
• ex; skeletal muscle glucose uptake

Question 21

endocytosis/exocytosis

Answer 21

• drug is engulfed by the cell via invagination of the cell membrane
• allows large nonlipids to enter cell

Question 22

What are the factors that affect drug distribution?

Answer 22

• tissue permeability (lipid based drugs vs protein based)
• blood flow (drug in circulation with gain greater access to highly perfused tissues like brain, kidney, skeletal muscle)
• binding to plasma proteins like albumin, bc only free drug can reach target tissue
• binding to subcellular components like lysosomes (antidepressants and antipsychotics), only free can reach target tissue

Question 23

Volume of Distribution (Vd)

Answer 23

the ratio of the amount of drug administered to the concentration of drug in the plasma

Vd = amount administered / concentration of drug in plasma

Question 24

Where are the drug storage sites in the body?

Answer 24

• adipose (primary) because many drugs are lipid-soluble
• bone is storage site for several toxic agents like heavy metals (lead) and also tetracyclines
• muscle
• organs such as liver and kidneys

Question 25

Adverse consequences of drug storage

Answer 25

• high concentrations stored in tissues can cause local damage (liver and kidneys, acetaminophen can cause severe liver damage)
• drug storage occurs when a reservoir “soaks up” a drug and prevents it from reaching the target site (so we must administer sufficient dose)
• prolonged effects or adverse effects can occur if the drug leaks out of a reservoir and enters target site long after the original dose should have been eliminated

Question 26

Describe two new drug delivery technologies

Answer 26

• controlled release preparations (timed release, sustained release, extended-release or prolonged-action preparations)
• implanted drug delivery system; small contained placed under skin in the abdomen that releases a small, measure dose of a drug on a pre-programmed schedule

Question 27

What methods are used so that specific drugs can reach their specific target tissues? What is the benefit of this?

Answer 27

benefit: less adverse/side effects

• add antibodies attracted to specific antigens (like for cancer cells)
• modify drugs so that it is activated only after it reaches a specific organ or tissue
• nanotech - small particles that can facilitate drug absorption or distribution, could help some drugs pass BBB into CNS, or help direct drugs to specific cells