Introduction to basic pharmacology and pharmacokinetics

Question 1

wHAT IS A DRUG

Answer 1

Potentially toxic substances that alter physiological processes

Question 2

What is pharmacokinetics

Answer 2

The study of the time course of the drug concentration in the body ie what the body does to the drug

Question 3

What is pharmacodynamics

Answer 3

The study of the relationship of drug []to pharmacological effects ie what the drug does to the body

Question 4

Routes of admin

Answer 4

*inhaled
*oral
*IV
Tropical
*Transdermal
*Parenteral
*Rectal
*Buccal / sublingual (it is used when a drug has a high first-pass metabolism rate )

Question 5

oral VS IV

Answer 5

1.Orally > first pass metabolism > gut metabolism ( food) and blood flow

(First pass metabolism: Elimination that occurs when a drug is first absorbed from the intestines and passes through the liver via portal circulation )

2. Parenteral IV
   * No first-pass metabolism
   * Bioequivalence is not necessary
   * Bioavailiability = 100 %

It is not affected liver metabolism,gut flora, blood flow, food

Question 6

The pharmacokinetics process: Absorption

Answer 6

1. Mechanisms of absorption
   (For a drug to produce a therapeutic effect it must be absorbed into the bloodstream and distributed through the circulation )

• Passive diffusion
• Facilitated diffusion ( carrier-mediated but no energy required )
• Pinocyosis : (Physical engulfment by cell, this is how small drugs are transported except for proteins . Vitamine A,D, E,K are absorbed this way)
• Active transport

Only the un-ionized form which is highly lipid-soluble can diffuse readily across a cell membrane therefore the more a drug is lipid-soluble =the more it can diffuse across the cell membrane = the more it is absorbed

Most drugs are diffused in the intestine

2. pKa and Drug Ionisation
   * acidic drugs are ionized in an alkaline environment and alkaline drugs are usually ionized in acidic environments

What is a pKa
a pH at which ionized forms are = to unionized forms of a drug

*The larger the pKa the small the extent of dissociation

2. Effects of pH and pKa on drug absorption
   * Acid drugs are better absorbed in an acid environment and basic drugs are better absorbed in basic environments

*Acids ionized: some in the stomach ,almost fully in the intestines and may therefore be absorbed in the stomach and trapped in the blood at low pKa,whereas high pKa almost none in the stomach,a little in the intestine and more in the blood and are therefore absorbed in the stomach

Bases ionized: some in the stomach bt almost none in the intestine and blood and therefore mainly absorbed in the intestines at low pKa , whereas at High pKa , almost fully in the stomach and some in the intestine and trapped in the stomach

Acid drugs: pH < pKa , the unionized form will dominate and if pH > the pKa, the ionized form will dominate

Base drugs: If pH < pKa the ionized form will dominate and if the pH> pKa the unionized form will terminate

If pH< pKa = protonated (HA & BH) form will dominate

If pH>pKa deprotonated ( A&B) form will dominate

HA and B can cross the membrane (bilayer)

Question 7

Pharmacokinetics process : Distribution

Answer 7

After absorption into the blood stream , drugs have to cross the capillary membrane to get into the interstitial fluid .

Distribution depends on :

• Physiochemical properties of a drug
• Tissue permeability
• CO and blood flow
• Perfusion of the tissue
• Transmembrane pH
• Binding plasma proteins and tissue receptors

2. A bound drug has no effect .

Amount bound depends on :

• free drug {}
• Protein []
• Affinity for binding site
• renal failure
• inflammation
• malnutrition
• competition from other drugs

Plamsa proteins that bind to drugs :
*Albumins Binds to many acidic and few basic drugs

*beta- globulins and alpha 1 acid glycoprotein bind to basic drugs

Drug distribution is affected by lipid solubility of a drug ,because fat soluble drugs can easily cross the fat stores and cell membrane barrier > wider distribution

*Hydrophilic drugs are easily eliminated in the body ,providing long lasting effects

barriers which prevent free distribution of drugs :
> BBB
> Placenta

Question 8

Metabolism

Answer 8

• Chemical conversion of drugs into metabolites by the body
• It is a clearing process that break down substance into water soluble form for easy excretion
• Primary site for drug metabolism is the liver followed by kidney , GIT and lungs

During metabolism drugs may be :

• Inactivated
• less active
• more active
• more toxic
• similar activity to parent compound

Drug phase metabolism :
* Phase 1 ; Metabolic modification eg hydrolysis ,reduction .,hydrolysis
Cytochrome p450 enzymes

*Phase 2 : Synthesis by conjugation forming conjugated metabolites

Aim is to make the drugs water soluble as possible so that they can be excreted

Question 9

Cytochrom P450 inducers and inhibitors

Everyday Right People Prevent Smoking

Queen Katwe envy cranberry grape juice

Answer 9

*Inducers 
Ethanol
Phenobarbitone 
Refampicin
Phenytoin 
Smoking
(
*Inhibitors 
Cimetidine 
Erythromycin
Grape juice 
Ketoconazole 
Quinidine

Question 10

Elimination

Answer 10

Routes of elimination :
kidney 
lungs 
sweat 
breast milk 
saliva 
feces 

Renal elimination 
>Active tubular secretion :
*Occurs in PTC 
*weak acids eg panicillin
*weak bases eg quinine 

> Tubular Reabsorption

• active / passive process
• Reabsorption governed by pH of tubular fluid ,pKa of a drug
• Acids best eliminated in urine
• bases best eliminated in acidic urine