Lecture 1 Last Section

Question 1

What is Subcutenous Injection ?

Answer 1

Parental Administration

Subcutaneous Injection :

subcutaneous injection is given in the fatty layer of tissue just under the skin
• there is little blood flow to fatty tissue, and the injected medication is generally absorbed more slowly, sometimes over 24 hours.
• e.g. growth hormone, insulin, epinephrine, and other substances.

Question 2

What is Intramuscular Administration?

Answer 2

Intramuscular administration:

Advantages 
– depot injections
 – reliable and predictable kinetics 
• Disadvantages 
– can be painful (self-administration difficult)

Question 3

Other routes of administration

Answer 3

Inhalation - Drugs administered by inhalation through the mouth must be atomized into smaller droplets than those administered by the nasal route, so that the drugs can pass through the windpipe (trachea) and into the lungs. … Inside the lungs, they are absorbed into the bloodstream.
• Topical - means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes including creams, foams, gels, lotions, and ointments.
– local effect
– systemic effect
Systemic effects are defined as those effects occurring in tissues distant from the site of contact between the body and the medical device or biomaterial.

Question 4

Pharmokinectics : Absorption What does it involve ?

Answer 4

involves the movement of drug into the systemic circulation

First, the drug needs to be introduced via some route of administration (oral, topical-dermal, etc.) and in a specific dosage form such as a tablet, capsule, solution and so on. Absorption depends upon the route of administration.

Question 5

What does Absoption depend on ?

Answer 5

Depends on drug’s ability to cross cell membranes and resist
Presystemic metabolism
– Presystemic metabolism is due to luminally secreted enzymes
(I) including pepsins, trypsin, chymotrypsin, elastase and
carboxypeptidase A/B, on brush border membrane bound
enzymes (II) including various carboxypeptidases and
aminopeptidases and on cytosolic enzymes.
– Presystemic metabolism affects drug’s bioavailability—
amount of drug that reaches systemic circulation intact and
its speed

Question 6

What are the factors which may affect absorption ?

Answer 6

• Acidity of the stomach
  Moreover some drugs are ionised by gastric pH and do not absorb very well (i.e. they are less lipid soluble in that state)
• Physiochemical properties: dissolution,
  solubility, thermodynamics
  Lipid water solubility. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water. …
• Presence of food in stomach or intestine
• Routes of administration: PO, IV, IM,
  subcutaneous, transdermal, sublingual, buccal,
  rectal, vaginal

With routes
The intestinal wall has extensive metabolic processes and transport mechanisms (e.g., P-glycoprotein) that affect absorption of drugs given via the oral route. ▴ Hepatic metabolism. Orally administered drugs are absorbed into the portal circulation and carried directly to the liver.

Question 7

Distribution

Answer 7

Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues. …

As the blood recirculates, the drug moves from the bloodstream into the body’s tissues.

Distribution: passage of agent through
blood or lymph to various body sites
• Many drugs are bound to circulating
proteins, affecting their ability to bind
to receptors; cross tissue membranes;
and be distributed, metabolized, and
excreted.

Binding to avoid breakdown

Question 8

Metabolism

Answer 8

Most drug metabolism occurs in the liver.
• First-pass effect (metabolism of drug by liver
enzymes before it reaches systemic circulation)
influences metabolism.

• Substances that are absorbed across the intestinal
wall enter blood vessels and are carried directly to
the liver (hepatic portal circulation).
• End-products of metabolism are metabolites

Question 9

What is First past effect ?

Answer 9

whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation.

Question 10

How does First pass effect work in Oral drugs ?

Answer 10

First-pass effect. Oral drugs are absorbed through the intestinal wall
and enter the hepatic portal circulation. They are taken directly to the liver for
metabolism before reaching the heart and circulating throughout the body.

Question 11

How does some routes of administeration avoid first pass effect ?

Answer 11

Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal, and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. ( Non-enteral administeration )

Question 12

Phamrokinectcis - Bioavailability

Answer 12

Bioavailability is usually assessed by determining the area under the plasma concentration–time curve

Question 13

Excretaion

Answer 13

Most drugs (or metabolites) are excreted by the kidneys. Three process can occur in renal excretion: glomerular filtration, tubular secretion and passive reabsorption. Some drugs are eliminated by the liver in the bile and excreted in feces. … The gastrointestinal tract can also be involved in elimination of some drugs.

Tubular Secretion :

Question 14

Tubular Secretion - Excretion

Answer 14

Tubule secretion involves two carrier systems – basic carriers which transport basic drugs (amiloride, dopamine, histamine), and acidic carriers for acidic drugs (frusemide, penicillin, indomethacin).

The process of tubule secretion can have a big impact on the speed that a drug is eliminated from the body. For example, penicillin readily enters the nephron by tubule secretion and is rapidly excreted from the body in the urine. In a situation where the therapeutic effect needs to be prolonged, agents can be administered that block tubule secretion to slow the excretion of the drug.

Question 15

Tubular Reabsoption ?

Answer 15

So, drugs and their metabolites enter the kidney tubule but some may be reabsorbed back into the blood stream. Reabsorption is referred to as passive diffusion since the process does not require energy.

Occurs because water is reabsorbed from the kidney tubules by diffusion.

Question 16

Firation

Answer 16

Clearance is the rate of elimination of substances from the blood. Systemic or total body clearance (Cltot) is calculated as the rate of elimination divided by serum concentration, where elimination can occur by both metabolic and renal clearance mechanisms.

Renal clearance (Clr) is the total amount of drug excreted over a specific time and will depend on glomerular filtration, tubular secretion and tubular reabsorption.

All drugs have different clearance rates, and this is important to know for determining the right dosage. Some have a high clearance, meaning that they are eliminated from the blood rapidly by the kidneys, such as the diuretic frusemide. Others have a low clearance due to inefficient excretion, so only low levels need to be administered to maintain their therapeutic level in the blood.

Question 17

What does other routes of Excretion include ?

Answer 17

Other routes of excretion include:
– Lungs
– Breast milk
– Sweat, tears, urine, feces
– Bile
– Saliva

Question 18

What are some factors which affect drug action ?

Answer 18

Factors Affecting Drug Action
• Age: affects metabolic rates, requiring
dosage adjustments.
• Gender: responses to drugs sometimes
differ.
• Body weight: dosages may require
adjusting for body weight and body
surface area.

Question 19

What are other factors which affect drug actioon

Answer 19

Diurnal rhythms: intensity of response to
drug may be affected by when it is given.
• Disease: dosages may need to be adjusted in
persons with kidney or liver disease. Because of the by action of the enzyme serotonin N-acetyltransferase

significantly reduce the nonrenal clearance and alter bioavailability of drugs predominantly metabolized by the liver and intestine.

Question 20

Other Pharmacologic Principles

Answer 20

• Toxicity: refers to drug’s ability to poison the body.
• Overdose: dose of drug that causes harm.
• Adverse drug reaction (ADR): any response to drug that is noxious, unintended, and occurs at doses normally used for prophylaxis, diagnosis, or therapy. • Side effect: an unintended drug effect; this can be beneficial

Question 21

Biotransformation ? And its four statfes

Answer 21

Bio transformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and drugs in the body. It is also needed to render non-polar compounds polar so that they are not reabsorbed in renal tubules and are excreted.

Oxidation - combining with oxygeneactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound

Typically, oxidation is the most common phase I reaction. The hepatic cytochrome P450 system is the most important of the phase I oxidation systems

Reduction: gaining electrons
is a chemical reaction in which the substrate gains electrons .Its most common in the biotransformation of xenobiotics.

Glucuronide conjugation is one of the most important and common Phase II reactions.

Hydrolysis: cleaving into simpler compounds
is a chemical reaction in which the addition of water splits the toxicant into two fragments or smaller molecules. … An example of hydrolysis is illustrated in the biotransformation of procaine (local anesthetic) which is hydrolyzed to two smaller chemicals

Conjugation - combining with glucuronic or sulfuric
acid, terminating biologic activity

These reactions involve covalent attachment of small hydrophilic endogenous molecule such as glucuronic acid, sulfate, or glycine to form water-soluble compounds, that are more hydrophilic. This is also known as a conjugation reaction. The final compounds have a larger molecular weight.