Pharmocology

Front 1

What is route of administration?
How can it be dictated?
How can it be exploited?

Back 1

ROUTE OF ADMINISTRATION.

Dictated
For example: RoA dictated for insulin – cannot be given orally since it’s a protein and will be chopped up by
the stomach – given IM or SubQ.

Exploited
Route of administration can be exploited for instance where transcutaneous is preferred to oral route to produce slower absorption, longer & more stable drug effects and dosing less often such as
(contraceptive patch) vs. oral contraceptives.

Front 2

What are the 13 routes of administrations?

Back 2

Routes of Administration
Oral (PO)
Intravenous (IV)
Intra-muscular (IM)
Intra Peritoneal (IP)
Sub cutaneous (Sub Q)
Intra-nasal
Inhalational
Transcutaneous (transdermal)
Epidural
Sub Lingual
Rectal
Pessary
Intrathecal

Front 3

What is the first pass effect?

How can we get around this?

Back 3

This occurs when a drug is absorbed and during distribution it first passes through the liver (common, since the
intestinal blood supply heads straight there).

This can be avoided by routes that avoid the liver such as sub lingual administration and rectal.

Front 4

What are 4 main permeation mechanisms?

Back 4

1)Aqueous Diffusion
Movement of the drug through water compartments such as cytosol, interstitial space. Includes the paracellular pathway. Can be affected by pH/pKa balance since most drugs are weak acids and bases

2)Lipid diffusion
Single most important and rate limiting.
Its what allows the drug to cross membranes.

3)Carriers and Transporters
Active transport or facilitated diffusion
Very good for large or insoluble substances
Drugs can use transporters since they resemble natural substrates for the transporters
Examples include P-glycoprotein, MDR1 and MRP2

4)Endocytosis and Exocytosis
Few drugs use this pathway
Drug is engulfed by the membrane which then pinches off to become a vesicle. The vesicle is lipid soluble
Examples include uptake of Vitamin B12 and the release of neurotransmitters due to electrical stimulation.

Front 5

What is Fick's Law of Diffusion?

Back 5

1

Front 6

What is Bioavailabilty?

Back 6

Bioavailability refers to the extent to and rate at which the drug or metabolite enters systemic circulation and is available at the site of action.

• Bioavailability of a drug is determined by the properties of the dosage form (which depend partly on its design and manufacture),as well as the drug's physicochemical properties, which determine absorption.

• Differences in bioavailability among formulations of a given drug can have clinical significance; thus, knowing whether drug formulations are equivalent is essential

• This was part of the problem with the very early generic drugs – the generic manufacturers couldn’t mimic proprietary formulations so differences in therapy occurred for the same drug.

Front 7

What are three types of equivalence?

Back 7

Chemical equivalence indicates that drug products contain the same compound in the same amount and meet current official standards; however, inactive ingredients in drug products may differ.

Bioequivalence indicates that the drug products, when given to the same patient in the same dosage regimen, result in equivalent concentrations of drug in plasma and tissues.

Therapeutic equivalence indicates that drug products, when given to the same patient in the same dosage regimen, have the same therapeutic and adverse effects.

Front 8

Define Therapeutic Index

Back 8

the therapeutic index (ratio of the minimum toxic concentration to the median effective concentration) of penicillin is so wide that efficacy and safety are not affected by differences in plasma concentration due to bioavailability differences in penicillin products.

• In contrast, for drugs with a relatively narrow therapeutic index, bioavailability differences may cause substantial therapeutic nonequivalence.

Front 9

What is the volume of distribution?

Back 9

The apparent volume of distribution is a theoretical volume of fluid into which the drug dose would have to be diluted to produce the concentration observed in plasma.

For example, if 1000 mg of a drug is given and the subsequent plasma concentration is 10 mg/L, 1000 mg appears to be distributed in 100 L (dose/volume = concentration; 1000 mg/x L = 10 mg/L; therefore, x = 1000 mg/10 mg/L = 100 L).

Front 10

What is volume of distribution 2!

Back 10

Volume of distribution has nothing to do with the actual volume of the body but is reflective of the distribution of the drug in the body.

For drugs that are highly tissue-bound and/or fat soluble, very little of a dose remains in the circulation to be measured. Hence, plasma concentration is low and volume of distribution is high.

Many acidic drugs (eg, warfarin and salicylic acid) are highly protein-bound and thus have a small apparent volume of distribution.

Many basic drugs (eg, amphetamine, meperidine) are extensively taken up into tissues and have an apparent volume of distribution larger than the volume of the entire body (several hundred liters).

More lipid soluble; not in blood --> Higher volume of distribution

More water soluble; in blood --> Lower volume of distribution