Pharmacology Revision

[Saifullah]

Can you please stay consistent though? I will be following this topic.

OK i will

[Saifullah]

If some of you guys are following this thread let me know if you understood what i wrote or if you need it more detailed or if you need clarification on certain points

[Saifullah]

I realised that i must touch on introductory pharmacology that way you will be able to understand terms that come later on

PHARMACOLOGY INTRODUCTION

Basically there are two sections to this

-Pharmacokinetics-Effect of body on drug
-Pharmacodynamics-Effect of drug on Body

This is like a simple explanation of each when we go into the details of them then you will understand what it means.

Pharmacodynamics
This is the effect of the drug on the body. A drug enters the body and certain mechanisms occur

1)Absorption of drugs
2)Distribution
3)Metabolism
4)Elimination

Let us explain Absorption of drugs first.....

Enteral Route-This can be either oral or sublingual (under the tongue)

Parenteral Route-This can be Intravenous, Intramuscular, Subcutaneous. this route is usually used to introduce drug directly into blood stream, and if the drug is poorly absorbed in from GI tract then this method is used! Or in emergency.

Other-This includes inhalation, intranasal, intrathecal, Topical, Transdermal and Rectal

[Saifullah]

Absorption of drugs is the transfer of a drug from its site of administration to the bloodstream.

In IV delivery (intravenous) absorption is 100% that is the total dose of drug reaches the systemic circulation. Drugs delivered in other ways may not be completely absorbed.

Most drugs have to pass through the gastrointestinal tract. They are absorbed either by passive diffusion, active transport or endocytosis/exocytosis.

The pH can effect the drug absorption as well, this is because some drugs are either weak acid or weak bases. From our chemistry we know that if a substance is uncharged it passes more easily through membranes.

Physical factors such as Blood flow to absorption site, total surface area available and contact time at absorption site can also effect absoprtion.

[Saifullah]

BIOAVAILABILITY

This is the fraction of administered drug that reaches the systemic circulation. It is expressed as a fraction. For example if 100mg of a drug administered orally and 70mg of this drug are absorbed unchanged then the availability is 0.7....70/100

Factors influencing Bioavailability

1)First-pass hepatic metabolism-When a drug is absorbed across the GI tract it enters the portal circulation first and then enters the systemic circulation. If a drug is rapidly metabolised by the liver then you will have less unchanged drug entering the systemic circulation decreasing bioavailabiliyy

2)Solubility of drug-Very hydrophilic drugs are poorly absorbed because of their inability to cross the lipid rich cell membranes. But if it is very hydrophobic it wont be able to be soluble in aqueous body fluid and cannot gain access to surface of cells. So therefore a drug should be hydrophobic, but hydrophilic enough to be soluble in aqueous solutions.

3)Chemical instability-Some drugs are unstable in gastric acid

4)Nature of drug formulation-Some drugs have capsule, enteric coatings and these alter rate of absorption.

There is a term called bioequivalence this is basically two related drugs with similar bioequivalence and similar times to achieve peak blood concentrations

Therapeutic equivalence is two similar drugs that have similar efficacy and safety.

[Saifullah]

All these points mentioned so far come under Pharmacokinetics

DRUG DISTRIBUTION
This is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and the cells of tissues. The delivery of drug from the plasma to the interstitium depends on

-Blood flow........If you inject IV thiopental its effects are on the central nervous system straight away (due to higher blood flow) but then later on spreads to muscles and adipose tissue causing it to be a short-acting anesthetic.

-Capillary permeability.......Blood brain barrier, so drugs have to be able to cross certain capillaries

-Binding of drugs to plasma proteins........Plasma albumin is the major drug-binding protein

[Saifullah]

VOLUME OF DISTRIBUTION

The volume of distribution is the hypothetical volume of fluid which a drug is dispersed. It is sometimes useful to compare the distribution of a drug with the volumes of the water compartments in the body.

The volume of distribution is given by the following equation:

VD=total amount of drug in the body/plasma concentration of blood.

[Saifullah]

So far I have gone quickly through the 2 parts of Pharmacokinetics, i didn't go into too much detail because it gets really complicated. It is good just to get an outline at first and then go into detail later on.

The two parts covered so far are
1)Absorption
2)Distribution

We can understand now the definiton of Pharmacokinetics being the effect of the body on the drug, or rather the way the body acts to change the drug while it goes through the body (absorption) to enter blood circulation and is then distributed.

After distribution comes metabolim and then elimination from the body...I will discuss that later on

[Saifullah]

Btw none of this is copy and paste, i could easily do that from wikipedia but i thought i will write according to simple terms and give outline rather than over-complicating things. In everything you should first understand the basic concepts and terminology. It is not a correct way to go so deep into things when you have not grasped the outline

[Laila]

If you wanna do medical later on, pharmacology undergrad will help a lot...

Well ya, that is what my parents advised me to do. To take at least a course in Pharmacology.

[Saifullah]

Ok Now lets talk about DRUG METABOLISM...(part of pharmacokinetics-3rd part)

Drugs are most of the time eliminated by biotransformation and/or excretion into the urine or bile. The process of metabolism transforms lipophilic drugs into more polar readily excretable products. The liver is the main site for drug metabolism but specific drugs may undergo biotransformation in other tissues such as kidney and intestines.

Reactions of drug metabolism

The kidney cannot efficiently eliminate lipophilic drugs that readily cross the cell membranes and are reabsorbed in the distal tubules. Therefore lipid soluble agents must first be metabolised by the liver using two general sets of reactions called PHASE I and PHASE II

Phase I-Converts lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group such as -OH or -NH2.

The phase I reactions utilise the P450 system (cytochrome p450 system also called microsomal mixed function oxidase).

Other Phase I reactions include amine oxidation, alcohol dehydrogenation, esterases and hydrolysis.

PHASE II This consists of conjugation reactions. If metabolite from phase I reaction is sufficiently polar then it can be excreted by the kidneys. However many Phase I metabolites are too lipophilic to be retained in the kidney tubules and need to be conjugated with an endogenous substrate like glucuronic acid, sulphuric acid, acetic acid or an amino acid.

[Saifullah]

DRUG ELIMINATION

This is the last part in Pharmacokinetics, starting from absorption and ending in elimination.

A drug has to be eliminated from the body, we take drugs to elicit a response in our body and so that it can do its job, after which it needs to be eliminated.

The most important route of elimination is via the kidneys into the urine.
Other routes include the bile, intestine, lung or milk in nursing mothers.

[eyeliner]

keep it coming saif

[Saifullah]

The next chapter will touch on Pharmacodynamics.

DRUG RECEPTOR INTERACTIONS AND PHARMACODYNAMICS

Most drugs exert their effects by interacting with receptors. Receptors bind drugs and inititate events leading to alterations in biochemical/biophysical activity of cell and function of an organ.

Drugs may bind to
-enzymes
-nucleic acids
-or membrane receptors

In each case binding leads to a biologic response.

Most receptors are named after the drug that interacts best with it, like histamine receptor.

On heart there are Beta receptors for norepinephrine and Muscaric receptors for acetylcholine.

There are 4 main receptor families

1)LIGAND-GATED ION CHANNELS-For example cholinergic nicotinic receptors
2)G PROTEIN-COUPLED RECEPTORS-alpha and beta adrenoceptors
3)ENZYME-LINKED RECEPTORS-Insulin receptors
4)INTRACELLULAR RECEPTORS-Steroid receptors

[Saifullah]

I find these chapters so boring...lol

Just a few terms i will explain then later we will continue with the autonomic system.

Agonist-If a drug binds to a receptor and produces a biologic response that mimics the response to the endogenous ligand it is knowns as an agonist. For example phenylephrine is an agonist at alpha-1-adrenoceptors because it produces effects that resemble the action of the endogenous ligand-norepinephrine

Antagonists-Are drugs that decrease the actions of another drug or endogenous ligand. They have no intrinsic activity and so cause no effect by themselves.
Antagonist