PHARM- Intro to pharmacology - week 1

Question 1

Define pharmacology?

Answer 1

The study of “drugs” AND their effects on life

Think of a “drug” as any exogenous chemical

The goal of pharmacology is to understand the mechanisms by which drugs interact with biologic systems

Question 2

Absorption

Answer 2

Drugs need to get from the site of administration to a target tissue

Most drugs are absorbed by passive diffusion

Some drugs use physiological transport processes

Absorption is also dependent on the route of administration

Question 3

Effect of pH

Answer 3

Many drugs are weak acids or bases

Only non-ionized forms of drugs can easily pass through a lipid bilayer

For orally administered drugs there are two significant pH compartments in the digestive tract

Stomach with low pH (normally around 1)

Small intestines with neutral pH (normally around 7)

Question 4

Bioavailability

Answer 4

The fraction of the administered dose of a drug that reaches the systemic circulation in an active (unchanged) form

Influenced by several factors

Intravenously administered drugs are 100% bioavailable by definition

Question 5

Distribution

Answer 5

In terms of tissue targets, this is influenced by:

Size of the organ

Blood flow

Drug solubility

Protein binding

Question 6

Metabolism

Answer 6

Aka biotransformation

The enzyme-catalyzed conversion of drugs to their metabolites

Most of this takes place in the liver, but the gut, kidneys, brain, lungs, and skin also contain drug-metabolizing enzymes

The primary goal is to inactive or detoxify foreign substances and to prepare them for excretion

Generally, the idea is to make a xenobiotic more water-soluble so that it can be readily excreted in by the kidneys

Not every drug needs to be metabolized in order to be eliminated

Not every drug is inactivated by metabolism

Prodrugs are common and are activated by metabolism

Metabolites may retain some degree of pharmacological activity (active metabolites)

Not every xenobiotic is immediately detoxified

Question 7

First Pass Effect

Answer 7

Drugs absorbed via the gut reach the liver via the portal vein before entering the systemic circulation

The degree to which the drug is inactivated by liver enzymes prior to entering the systemic circulation substantially alters the drug’s bioavailability

Question 8

Phase 1 metabolism

Answer 8

Primary goal is to introduce or open up a binding site for hydrophilic compounds to be added later by phase II mechanisms

Oxidative reactions by far the most common

Microsomal cytochrome P450 (CYP450) system

Question 9

Phase 2 metabolism

Answer 9

Not all drugs require phase I metabolism prior to phase II but most do

These reactions essentially conjugate a water-soluble molecule to the spot opened up by phase 1 reactions

In many instances, this means conjugating something to an available hydroxyl group

Each phase 2 mechanism has its own enzyme that catalyzes the reactions

Question 10

Enterohepatic circulation

Answer 10

Glucuronide conjugates are excreted in bile

Some commensal gut bacteria have glucuronidase enzymes which can cleave the glucuronide off the metabolite resulting in the parent drug being able to be reabsorbed

Example in photo

Question 11

Elimination

Answer 11

Most water-soluble drug metabolites are excreted by the kidneys

Various mechanisms exist throughout the sections of the nephron

Lipid-soluble drugs are excreted in the distal tubule if they’re small enough

Lipid-soluble drug metabolites and glucuronide-conjugates are excreted by the liver into bile and are excreted in feces

Question 12

Pharmacodynamics

Answer 12

Essentially the study of a drug’s mechanism of action

Drug-receptor characterization and mechanics

Signal transduction mechanisms

Question 13

Agonist

Answer 13

Agonist – a substance that initiates a physiological response when combined with a receptor

Question 14

Antagonist

Answer 14

Antagonist – a substance that interferes with or inhibits the physiological action of another substance

Question 15

Competitive

Answer 15

Competitive – used to describe when two substances use the same binding site on a receptor

Question 16

Allosteric

Answer 16

Allosteric – used to describe when a substance binds to a receptor away from an active binding site but still alters the physiological effect

Question 17

Measures of safety

Answer 17

Therapeutic Index (TI)

LD50 – dose at which causes death in 50% of individual (animal)

ED50 – dose at which causes a therapeutic response in 50% of individuals (human)

TI=LD50/ED50

Question 18

Prescribing Standards

Answer 18

Generic name – most suitable drug name to use as it is standard across all jurisdictions

Brand name – registered trademarked name of a drug used in marketing

Example: atorvastatin vs Lipitor®

It is generally advised to write full words as much as possible and to avoid abbreviations

Never abbreviate the drug name

Use generic names unless you specifically want a brand name drug dispensed

Question 19

Prescription requirements

Answer 19

Date
Name and address of patient
Name, strength, quantity and form of drug or ingredient(s)
Directions for use (include frequency or interval or maximum daily use)
Refill authorization (number and interval between refills)
Name and college ID of practitioner
Signature of practitioner

Question 20

Pharmacology: Pharmacokinetics vs pharacodynamics

Answer 20

Pharmacokinetics: Dose of drug administered–> absorption, distribution, metabolism, excretion

Pharmacodynamics: Drug concentration in blood or target tissue –> receptor binding, signal transduction, pharmacological effects, dose-response