Lecture 2: Principles of Pharmacology II

1. protein bound

2. free

1. protein bound

2. free

When drugs get into the body, they exist in two states:

Free drugs floating in plasma

Only drugs available to be used by receptors:

Albumin

Most abundant protein in blood

1. Blood test

2. Patient assessment

How to tell albumin levels in blood [2]

1. Chronically thin

2. low appetite

3. malnourished

when assessing for low albumin levels, look for: [3]

affinity

“attraction”

lower

If a drug does not have much protein binding, then it is typically a (lower/hgiher) dose:

Biotransformation

The chemical changing of a drug

Enzymes

What alters drug structure in drug metabolism?

Liver

The primary site of drug metabolism

1. Younger children/infants have less mature livers

2. Older people may have liver degeneration

How can age impact drug metabolism? [2]

Auto-induction

When drugs make their own metabolizing enzymes to speed their own metabolism. Can also induce enzymes for a different drug

Alcohol and acetaminophen. They compete for metabolism binding sites in the liver

there is competition between what drugs in the liver? (example)

Better nutrition, better metaolism will be

Nutritional status on metabolism:

Hepatic first-ass effect

When drugs first pass through the liver, a lot will be lost/inactivated through first pass of the hepatic portal circulation

Sublingual goes directly into the bloodstream. Does not pass through hepatic portal circulation. There is no amount of the drug lost in hepatic first pass effect, unlike oral meds

explain why sublingual doses of certain drugs will be smaller than PO

1. less lipid solble

2. inactivation of drug

3. increased therapeutic action

4. Activation of prodrugs (active molecules)

What needs to happen to drugs to be excreted? [4]

Drugs cannot stay in the body forever. If they stayed, the body would become toxic.

Why is drug metabolism necessary?

lipid solubility goes down so that it can be excreted (dissolved in urine)

What happens to lipid-slubility of drugs as they are ready to be excreted?

1. Glomerular filtration

2. Passive tubular reabsorption

3. Active tubular secretion

Drugs are excreted via three processes in the kidneys:

Glomerular filtration

Movement from blood to urine

Passive reabsorption

Movement of something (ex: something that is lipid soluble) from filtrate back into the blood. Things that are not polar or ionized.

No. Only free drugs can be excreted.

Can drugs bound to proteins be excreted?

GFR

Measure of kidney function. More reliable in older people

Creatinine

Levels that are tested to kidney function. Excess of this in the liver means kidneys are doing a poor job of filtering

1. breast milk

2. bile

3. lungs

4. sweat

5. saliva

Non-renal routes of excretion [5]

Placebo

When you anticipate and want a drug to work, and there is some therapeutic effect

Onset

The point at which you start to feel the effects of a drug

Peak

Point at which the drug is at it’s most effective action

Duration

How long you feel the effects of the drug

Minimum effective concentration

Drugs below THIS amount will not have an effect

Therapeutic range (also called therapeutic index)

Range at which a drug is safe. Between the toxic concentration and minimum effective concentration

Toxic concentration

If drug levels reach above this level, it will be toxic

Loading dose

Giving an extra dose of a drug at the beginning to saturate tissues and get it into therapeutic range

Maintenance dose

Doses of drug given to keep it in therapeutic range (mainly see it with antibiotics)

Half life

Time required for the amount of drug in the body to decrease by 50%

Half-life of the medication.Shorter half life= shorter interval of doses

What determines the dosing interval?

3 hours

Half-Life of morphine

Plateau principle

The steady level achieved after repeatedly administering dosees of a drug. Amount eliminated between doses equals the amount administered

4 half-lives

How many half live will it take to reach a plateau?

minimal amount of drug to get maximum response

Rule of thumb for medication dosing:

The relationship between size of an administered dose and the intensity of the response produced

Dose-drug relationship means:

Maximal efficacy

The larest effect the drug can produce (height of dose-response curve)

Relative potency

Amount of drug we must give to elicit an effect (length of the dose-response curve)

Agonist

Molecules that activate receptors, binding to them and mimicing the actions of the body’s own regulatory intrinsic activity

Intrinsic activity

What a drug does when it binds to a receptor is called:

Angtagonist

Drug prevents receptor activation. Produces effects by blocking receptor activation by endogenous regulator molecules and drugs.