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General principles of pharmacology د.غادة عبد الرحمن طاقة \ 2018

INTRODUCTION
Lecture 1

* pharmacology

Pharmacology: The study of drugs
( Greek pharmacon: drug)

PHARMACOLOGY :
is the science dealing with interactions between chemicals ( drugs ) and living systems.

* Drug
It is the single active chemical present in the medicine that is used for diagnosis , prevention , treatment and cure of disease .
OR It is a chemical substance that interact with living system to produce response

DEFINSION

MEDICAL PHARMACOLOGY
The science of substance used to prevent,
diagnose, and treat disease.
TOXICOLOGY:
IS that branch of pharmacology that deals with the undesirable effects of chemicals in biological system.

Medication Terms

Trade : Brand name manufacturer uses in marketing the drug
Indications : Most common uses of the drug
Contraindications
Situations in which a drug should not be used
May cause harm to the patient
May have no effect in improving the patient's condition
Dose : How much of the drug should be given
Administration : Route by which the medication is administered
Actions : Desired effects a drug has on the patient / body systems
Side effects : Actions of a drug other than those desired

DRUG- BODY INTERACTION

Interaction divided into 2 classes :
1- Pharmacokinetic phase-
Pharmacokinetics: (The Life Cycle of a Drug)
The process by which a drug is absorbed, distributed, metabolized and eliminated and Excretion by the body
2- Pharmacodynamic phase-
Pharmacodynamic : The interactions of a drug and the receptors responsible for its action in the body

Dynamics Kinetics

Dose Administered
Circulation
Absorption
Tissue
Kidneys/
Liver
Distribution
Elimination
Drug at Effect Site
Efficacy
Adverse Events
Metabolism

1- Pharmacokinetic phase

Describes how the body works on drugs (refers to what the body does to a drug,)pharmacokinetic properties determine:A- the speed of onset of drug action,B- the intensity of the drug’s effect,C- and the duration of drug action

pharmacokinetic :

consists of four major processes;
Absorption: drug absorption from the site of administration permits entry of the therapeutic agent (either directly or indirectly) into plasma.
Distribution: the drug may then reversibly leave the bloodstream and distribute into the interstitial and intra cellular fluids.
Metabolism: the drug may be biotransformed by metabolism by the liver, or other tissues.
Elimination: the drug and its metabolites are eliminated from the body in urine, bile, or feces.

*

*

* PHARMACOKINETICS

Factors effect on pharmacokinetic :
-route of administration
- dose
- onset
-peak time
-duration
-frequency of administration
(The faster the absorption, the quicker the Onset but the shorter the duration )

*

* Cont.

All kinetic process involve transport of drug across biological membrane which are bilayer of phospholipids and cholesterol molecules
The drugs are transported across the membranes by
1- passive diffusion and filtration
2- specialized transport


*

*

Absorption

Is transfer of a drug from its site of administration to bloodstream . The rate and efficiency of absorption depend on the rout of administration .1- passive diffusion : the drug moves from a region of high concentration to lower concentration. And not involve carrier . the majority of drugs gain access to the body by this mechanism . Lipid soluble drugs readily move across most biological membrane whereas water – soluble drugs penetrate the cell membrane through aqueous channels or pores .

Water-soluble

Ionized (have electrical charge)
Crosses through pores in capillaries, but not cell membranes

Lipid(fat)-soluble
Non-ionized (no electrical charge)
Crosses pores, cell membranes, blood-brain-barrier

2-Active transport : Its capable of moving drugs against a concentration gradient ( from low concentration drug to higher concentration )The drug need specific carrier proteins to cross membrane . Is energy – dependent (ATP)

* 3- Endocytosis and exocytosis

for large size the cell membrane
eg vit B12 (Endocytosis)
certain neurotransmitter eg norepinephrine (exocytosis)

Factors Affecting Drug Absorption

1. Transport
active vs. passive
2. pH
3. Physical factors
blood flow
surface area
contact time

ATP
ADP
+ Pi
A-
BH+

FACTORS AFFECT DRUG ABSORPTION

2. PH
Drug are either weak acid or weak base
Weak acid
HA H+ + A-
Weak base
BH+ B+H+

pH of the medication

The pH of the tissues at the site of administration and the dissociation constant (pKa) of the drug will determine the amount of the drug present in the ionized state ( water soluble ).
This amount will determine the easy with which the drug will penetrate or travel through the tissues.

Lipid soluble

Water soluble


* Drugs pass through ,membrane more easy if it is uncharged (not ionized) i.e (HA) and (B) , while charged (ionized ) one can not passes
- the ratio between charged and uncharged is determined by PH at site of absorption and by the strength of acid and base i.e (pka)

* Cont.

Pka : is the negative logarithm of acidic dissociation constant of the weak electrolytes .
The lower pka of drug the stronger the acid ,conversely the higher pka the stronger the base

* Cont.

e.g. in case of infection low PH (acidic tissue) cause less effect of L.A (weak base). i:e the PH > pKa ( more drug in ionized form)
e.g. acidic drug (aspirin) unionized at acid gastric PH and absorbed from stomach

* Ion Trapping:

Is to accelerate excretion of drug out of body (prevent absorption from tubules) by adjusting the urine PH .
Thus the weak acid are usually excreted faster in alkaline urine while weak base excreted faster in acidic urine

2.PHYSICAL FACTOR

A-Blood flow

B-Total surface area

C-Contact time at absorption surface

A-Blood flow to the absorption site

Blood flow to intestine is much greater than stomach thus absorption from intestine is favored over that from the stomach .
B-Total surface area
The intestine has a surface rich in microvilli thus the absorption of drug across the intestine is more efficient
C-Contact time at absorption surface
If drug moves through the GI tract very quickly, as in sever diarrhea ,it is not well absorb .
Conversely , anything that delays the transport of the drug from the stomach to the intestine delays the rate of absorption of the drug.

BIOAVAILABIITY

Definition:
Fraction of a drug that reaches systemic circulation after a particular route of administration .

eg if 100mg of a drug are administered orally and 70 mg of this drug are absorbed unchanged , the bioavailability is 0.7 or
70 %

Bioavailability=AUC ORAL *100/ AUC injection

Serum Concentration
Time
Injected Dose
Oral Dose

BIOAVAILABIITY

Affected by:
1- 1st pass metabolism(First-pass hepatic metabolism) (eg: Lidocaine)
2- Solubility
3- Instability (eg: Penicillin G, insulin )
Instable in oral administration
4-nature of drug formation : Physical properties of the drug (hydrophobicity (lipid soluble), pKa, solubility).
Another factors : The drug formulation (immediate release, delayed release, etc.)
If the drug is administered in a fed or fasted state
Gastric emptying rate , Interactions with other drugs, Age , Diet , Gender , Disease state

1- 1st pass metabolism (eg: Lidocaine,)

It mean: When a drug is absorbed across the GIT , it enters the portal circulation before entering the systemic.
If the drug is rapidly metabolized by the liver , the amount drug that reach to the circulation is decrease
Many drugs such as propranolol or lidocaine undergo significant biotransformation during passage through the liver .

[Note: First-pass metabolism by the intestine or liver limits the efficacy of many drugs when taken orally.
For example, more than 90 % of nitroglycerin is cleared during a single passage through the liver, which is the primary reason why this agent is administered via the sublingual route].

First Pass Metabolism Occurs Primarily in the Liver and Gut

2- Solubility very hydrophilic(water soluble ) drugs are poorly absorbed because of their inability to cross the lipid – rich cell membranes. highly lipid soluble drugs easily cross cell membrane .

3- Instability

some drug such as Penicillin G, are unstable in PH of the gastric content
insulin destroyed in the GIT due to destroy by enzyme.
4-nature of drug formation
drug absorption may be alter by factor unrelated to the chemistry of the drug
Such as : particle size ,
salt form ,
enteric coated ,
dispersing agents .




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