Pharmacology

study of the mechanism of action of drugs within the body and how drugs produce their effects in the body

study of drug reactions in the body that are unanticipated or unusual, and may have a hereditary basis for the response

study of drug actions as they move through the body; the way the body absorbs, distributes, metabolizes, and excretes drugs; mathe

pharmacology

study of drugs used to prevent, treat or Dx. disease

pharmacy

toxicology

3 drug names

chemical name

generic name

trand name

receptors

drug enchance

drug that diminish

drug that blocks

affinity

high affinity

low affinity

drug potency

effective dose

toxic dose (TD)

therapeutic index

the safer the drug is considered to be; in general nonprescription drugs have much higher therapeutic index than prescription drugs

schedule drugs classes

C-I

C-II

C-III

C-IV

C-V

routes drugs take to get into the body

promoting a change in cellular function

blocks the receptor usually resulting in no direct biological effect

* refers to molecule with a center of three-dimensional asymmetry.

molecules which are not superimposable on (cannot be made to coincide with) their mirror image. achiral molecules can be superimposed on its mirror image.

molecules having opposite shapes) are pairs of molecules existing in forms that are mirror images of each other (right-& left-hand) but that cannot be superimposed

molecule has 2 asymmetric centers, the molecule is referred to as

item appears identical to its image in a mirror it is said to be

All molecules are _______ when they have one stereogenic (asymmetric) carbon.

transport of solid matter or liquid into the cell utilizing a coated vacuole or vesicle.

Transport of materials out of a cell using a vesicle that first engulfs the material and then is extruded through an opening in the cell membrane.

Most drug have molecular weights between:

General term having to do with actions of the body on the drug:

Most common mechanism of drug permeation

Drug with this ionization property most likely to diffuse from intestine (pH 8.4) to blood (pH 7.4)
1. weak acid (pKa 7.4)
2. weak base (pKa 8.4)
3. weak acid (pKa 8.4)
4. weak base (pKa 6.4)
5. weak acid (pKa 6.4)

Weak organic acid, pKa 6.5. Percent ionization at pH 7.5
a 1%
b 10%
c 50%
d 90%
e 99%

Drug delivery method LEAST suitable for long term (days to weeks) slow release.

a pellet implant under the skin (subcutaneous)
b time release capsule
c i.m. injection of a drug- oil suspension
d transdermal patch
e none of the above

Mechanism(s) of drug permeation:
A lipid diffusion
B aqueous diffusion
C use of carrier molecules
D endocytosis and exocytosis
E all of the above

Increasing ionization at pH ABOVE pKa:
A weak acid
B weak base

Drug-transport system described as "energy requiring":
A glomerular filtration
B facilitated diffusion
C active transport
D B & C
E A, B & C

Bond type that is seen in some drug-receptor interactions and tends to very strong, often nearly irreversible:
A hydrophobic
B electrostatic
C covalent
D A & C
E B & C

Pharmacological antagonists:
A cause receptor down regulation
B prevent binding of other molecules to the receptor by their binding to the receptor
C atropine (blocks ACh action on the heart
D A & B
E B & C

Faster drug absorption:
A lung
B stomach

Most important factor influencing drug absorption rate following intramuscular injection:
A needle diameter
B rate of administration
C injection site blood flow
D injection volume

Saturable transport system(s):
A facilitated diffusion
B passive diffusion
C active transport
D A & B
E A & C

Passive diffusion (aqueous or lipid environment): most common

Active transport: important for some drugs, particularly larger molecules.

within large aqueous components (e.g.,interstitial space, cytosol)

across epithelial membrane tight junctions

across endothelial blood vessel lining

through aqueous pores: allows diffusion of molecules with molecular weights up to 20,000 -- 30,000.

represents a tendency for molecules to move in the direction of higher concentration to lower concentration in accord with random molecular motion. A traditional way of thinking about this is to imagine a fluid-filled container which is two sections divided by an imaginary plane. The solution on one side is more concentrated in terms of some dissolved substance that is the solution on the other side of the boundary plane.

describes passive movement molecules down its concentration gradient.

Plasma protein-bound drugs cannot permeate through

Charged drugs will be influenced by _____________ {membrane potentials, important in renal, trans-tubular transport}

Most important barrier for drug permeation due to:

many lipid barriers separating body compartments

Ionization state of the drug is an important factor: charged drugs diffuse-through lipid environments with _______________.

Lipid: aqueous drug partition coefficients described the ease with which a drug moves between _________ and __________ environments

uncharged form

charged form

a weak acid at acid pH will be more ______________because it is uncharged and uncharged molecules move more readily through a lipid (nonpolar) environment, like the some membrane, than charged molecules

a weak base at alkaline pH will be more _____________because at alkaline pH a proton will dissociate from molecule leaving it uncharged and again free to move through lipid membrane structures

________ diffusion depends on adequate lipid solubility

Drug ionization reduces a drug's ability to cross a _________ bilayer.

___________IS a neutral molecule that can form a cation (positively charged) by combining with a proton

___________is a neutral molecule that dissociates into an anion (negatively charged) and a proton (a hydrogen ion)

Peptides, amino acids, glucose are examples of molecules then enter cells through _______________mechanisms

______________ describes an energy requiring process which is saturable, meaning that transport is probably against the concentration gradient and involves a finite number of carriers, hence the process must be saturable when all carrier sites are filled.

limited number of carrier sites--once those sites are filled, transport rates cannot be increased.

A property of carrier systems is that process is subject to

Entry into cells by very large substances (e.g., iron vitamin B12 -- each complexed with its binding protein -- movement across intestinal wall into the blood)

Following neuronal electrical activation of nerve endings, two steps may be initiated:

Incomplete absorption following oral drug administration is common:

For example -- only 70% of a digoxin dose reaches systemic circulation.
factors are:

not be well absorbed --cannot cross cell membrane lipid component

soluble (hydrophobic) drugs may not be soluble enough to cross a water layer near the cell membrane.

To increase excretion

excreted faster in alkaline pH (anion form favored)

excreted faster in acidic pH (cation form favored)

Body fluids where pH differences from blood pH favor trapping or reabsorption:

fetal pH is higher or lower than maternal pH

Most convenient, most economical route of administration of drug

Oral Administration
Disadvantages:

Factors determining rate of drug effect onset

Drug ionization state:

nonionized (lipid-soluble) forms favor absorption

weak acids may be highly ionized in the alkaline intestinal pH (not favoring absorption) but this effect is counterbalanced by the large surface-area effect

drugs which are weak acids are readily absorbed in the stomach

Drugs absorbed from the GI tract passes through the portal venous system then through the liver and finally into the systemic circulation when drugs interact with receptors in target tissues.

Extensive hepatic metabolism/extraction result in minimal drug delivery to the systemic circulation for certain agents.

Drugs with large first pass effect exhibit significant differences in pharmacological effects comparing oral vs. IV administration

Examples:

propranolol

lidocaine

Transdermal Administration

Advantages:

Factors contributing to reliable transdermal drug absorption:

Low _______ administration of drug may allow the drug to enter the systemic circulation without passing through the liver

Proximal rectum administration: Absorption into superior hemorrhoidal veins then enters the portal venous system then to the liver (possible first pass hepatic effect) and finally into the systemic circulation

Low rectal administration of drug may allow the drug to enter the systemic circulation without passing through the liver

Generally unpredictable pharmacological responses for the above reasons

Rectal mucosal irritation possible

Ensures active drug absorption

subcutaneously intramuscular injection: more rapid/predictable than oral administration route

only route of administration acceptable for:

uncooperative patients

unconscious patients

Parenteral Administration


Factors the determine rate of systemic absorption:

Advantages of IV administration

First-pass Elimination:

Transport sequence:

Some drugs which have relatively low _______________ are not given orally because of concern of metabolite toxicity -- lidocaine is an example (CNS toxicity, convulsions)

Some drugs that exhibit high or low extraction by the liver are given orally.

Some examples -- desipramine (Norpramin), imipramine (Tofranil), meperidine (Demerol), propranolol (Inderal), amitriptyline (Elavil, Endep), isoniazid (INH).

High extraction ratio drugs show interpatient bioavailability variation because all of sensitivity to:

Drugs poorly extracted by the liver

Avoiding the first-pass effect:

Pulmonary uptake:

First-pass pulmonary effect magnitude not affected by:

is the ratio between the amount of drug in body (dose given) and the concentration of the drug (C) measured in blood or plasma.

Vd formula

Factors influencing the volume of distribution:

_____________ is especially important for insuring appropriate long-term drug dosing -- correct steady-state drug concentrations

Clearance of a given drug is usually constant over the therapeutic concentration range because:

__________ most important organs for unchanged drug/drug metabolites elimination

Water-soluble compounds exhibit more efficient renal excretion compared to ___________compounds (emphasizing the importance of metabolic conversion of lipid-soluble drugs to water-soluble metabolites)

Factors in renal excretion

Factors in renal excretion:

Glomerular filtration-- important considerations:

Factors in renal excretion:
Tubular secretion (active process)-- important considerations:

Factors in renal excretion
Passive tubular reabsorption-- important considerations:

drug elimination following metabolic transformation of the parent drug to metabolites

Since elimination is not "saturable", elimination is typically first order and directly proportional to drug concentration:

Other factors affecting renal clearance:

Factors affecting hepatic clearance:

Changes in the intrinsic clearance
Social factors:

Changes in the intrinsic clearance
Dietary considerations

Changes in the intrinsic clearance
age:

time required to decrease the amount of drug in body by 1/2 during elimination (or during a constant infusion).

Factors affecting t1/2:

Drug Accumulation

fraction of unchanged drug that reaches systemic circulation following administration (by any Route of Administration)

Major factors that reduce bioavailability to less than 100%: