Pharmacokinetics: administration and absorption

Question 1

Enteral routes of administration (3)

Answer 1

• Oral (p.o.)
• Sublingual
• Rectal

Question 2

Parenteral (injection) routes of administration (4)

Answer 2

• Intravenous (IV)
• Intraperitoneal
• Intramuscular (IM)
• Subcutaneous

Question 3

Parenteral (non-injection) routes of administration (4)

Answer 3

• Inhalation
• Intranasal
• Transdermal
• Topical

Question 4

Enteral definition

Answer 4

Passes through the intestine

Question 5

Oral administration (p.o.)

Answer 5

• passes through the stomach into the intestines where it is absorbed
• food delays the drug reaching the intestine (slower absorption)

Question 6

What does the rate of absorption depend on?

Answer 6

The % of the drug molecules that are not ionized, which depends on if the drug is a weak base or acid, the pH of the solution the drug is dissolved in, and the pka of the drug

Question 7

Which drugs are lipid soluble and why does this matter?

Answer 7

Non-ionized drug molecules are lipid soluble. This matters because cell membranes are 2 layers of lipid molecules sitting side by side.

Question 8

pH of stomach and intestines. Weak acids and weak bases mostly ionized or non-ionized here?

Answer 8

stomach: 1-1.5
intestines: 2.5
- weak acids are mostly non-ionized
- weak bases are mostly ionized (except caffeine, aka - 0.5)

Question 9

Parenteral (injection) definition

Answer 9

does not involve alimentary canal (GI)

Question 10

Injection and the order of rate of absorption of the different routes

Answer 10

Dissolved in solution (vehicle) with no pharmacological effect (saline). Where and how deep the injection gives different rates of absorption (IV>IP>IM>SC)

Question 11

IV (intravenous) definition, effects, uses, and disadvantages

Answer 11

Inject into the vein (rapid onset of effect so a precise dose control is needed). Commonly used in animals and is almost never used in humans. Disadvantages: risk of puncturing intestines or other organs, if there is an adverse reaction, you can’t recall the drug like you could for oral (activated charcoal), veins could collapse if used too frequently

Question 12

IM (intramuscular) definition, where in humans, which drugs are best, how to slow, disadvantages

Answer 12

Injection into a large muscle. The deltoid or gluteus Maximus in humans. Water soluble drugs are well absorbed because they can make their way through the little gaps in capillaries to move from the muscle to the blood vessels. Can slow by injecting a drug that constricts blood flow. Disadvantage: painful

Question 13

SC (subcutaneous) definition, where in humans and animals, advantages, disadvantages

Answer 13

Injection beneath the skin. In humans, the arm or thigh. In animals, in the loose skin on the back. Advantage: less risk of hitting a vein, less painful than IM, slow, steady absorption (ex: contraceptive). Disadvantage: limit to volume (too large causes irritation)

Question 14

Factors affecting absorption from parental sites (2)

Answer 14

1) blood flow (the higher the blood flow to the tissue that the drug is injected into, the more rapid the absorption. The blood from to peritoneal cavity is greater than to muscles, is greater than to skin

2) diffusion to capillaries: water soluble drugs enter the blood through pores and lipid soluble drugs dissolved through the cell walls. Move into capillaries by diffusion

Question 15

Depot injections definition

Answer 15

Highly lipid soluble drugs dissolved in a viscous oil (sesame oil) and injected SC or IM. They slowly diffuse form the oil (depot) into the blood and so a prolonged effect is produced.

Question 16

Inhalation (drugs as gases) definition, how drug diffuses, advantage

Answer 16

Rapidly absorbed into the blood by diffusion because the lung surface is most and richly supplied with blood capillaries (high blood flow). If the concentration in the blood is greater than in the air, the drug will diffuse form the blood to the air (exhaled - alcohol breathalyzer.) Advantage: precise control of blood levels (general anesthesia)

Question 17

Inhalation (drug particles in smoke) definition, how drug is absorbed, speed

Answer 17

Dissolve in mucous lining and absorbed into the blood. Delivers the drug to the brain faster than IV injection in limb because route (lung to heart to brain) is faster.

Question 18

Intranasal definition, effect

Answer 18

Dissolved in the mucous membranes of the nasal cavity and absorbed into the blood. It has local effects (effects where it was administered). Bypasses 1st pass metabolism and the blood brain barrier and so goes directly into the CSF

Question 19

Transdermal definition and characteristics

Answer 19

absorption across skin into capillaries. The skin is a sheet of flattened cells that are densely packed with keratin (waterproof). Therefore, slow rate of absorption (estrogen, nicotine)

Question 20

Factors that determine how a drug is distributed in the body (6)

Answer 20

1) degree of lipid solubility
2) Ion trapping
3) Blood brain barrier (BBB)
4) passive and active transport
5) protein binding
6) placental barrier

Question 21

Degree of lipid solubility

Answer 21

• determines the extent and ease of distribution. As lipid solubility increases the drug molecules can move more easily through the body. Can measure the lipid solubility using olive oil partition coefficient. High lipid solubility, ends up in body fat and a slow release over time.

Question 22

Ion trapping

Answer 22

• the intestine to the blood are 3.5-7 pH. So, a weak acid is mostly non-ionized in the intestine and mostly ionized in the blood. This would make it less likely/slower to get into the brain. Bases are trapped in low pH environments and acids in high pH environments.

Question 23

Blood brain barrier (BBB)

Answer 23

• a protected environment (protected from water soluble substances, not lipid soluble). Astrocytes line the outside of capillaries. They close pores and prevent non-lipid soluble substances from entering. Non-lipid soluble substance require by the brain are pumped across the BBB

Question 24

Passive, facilitated, and active transport

Answer 24

passive transport = diffusion (lipid soluble molecules dissolve across the membrane down a [] gradient)
- facilitated transport: non-lipid soluble molecule attaches to lipid soluble carrier protein and passes across the membrane.

active transport: carrier protein requires energy to operate. The molecule is pumped across the membrane up a [] gradient (not common)

Question 25

Protein binding

Answer 25

Drug molecules bind reversibly to protein molecules in the blood. This makes a reservoir of the drug that is not available for distribution when bound. The degree of binding depends on the drug concentration and as the concentration decreases, bound molecules are released (the less bound the drug, the more efficiently it moves between compartments)

Question 26

Placental barrier and risks

Answer 26

protected environment for the fetus (similar to BBB). Separates the blood of the mother and the fetus. Only for water-soluble drugs. Lipid soluble drugs diffuse across barrier fast. Risks: the BBB is not fully developed until 1-2 years. The fetus lacks enzymes to be able to metabolize certain drugs, free plasma proteins to bind to drugs, greater blood flow to the brain.