I-Routes of drug administration
II- Absorbtion of drugs
III-Bioavailability
IV-Drug distribution
VI- Drug metabolism
Drug structure
I- Routes of drug administration :
2 major routes
A- Enteral
Oral
the most common route
the most variable mode in amount of drugs reach the target tissues
some drugs are absorbed from the stomach
most drugs are absorbed from the duodenum
most drugs absorbed from GIT enter the portal circulation and encounter the liver before they are distributed in the general circulation
first pass metabolism by intestine or liver limits the efficacy of many drugs when taken orally
Sublingual
the drug diffuses to the systemic circulation directly
Rectal
fifty percntage of the drug bypass the portal circulation
Useful if the drug
destructed by the intestinal enzymes
destructed by the low pH of the stomach
induce vomitting or the patient himself is vomitting
B- Parenteral
I.V
the most common parenteral route
drugs avoid first pass metabolism
permit a rapid effect
permit the maximal degree of control over the circulating levels of drug
the rate of infusion must be carefully controlled
I.M
main route used for depot preparations which dissolves slowly providing a sustained dose over an extended period of time
used also for many aquous solutions of drugs
S.C
as I.M it requires absorbtion
slower than I.V
minimizes the risks associated with I.V injections
Others
Inhalation
provides rapid delivery of drug producing rapid effect almost as that of I.V
Intranasal e.g salmon calcitonin used in osteoporosis
Intrathecal e.g methotrexate in leukemia
Intraventricular
Topical when local effect of the drug is required
Transdermal e.g nitroglycerine when used as antianginal
II- Absorbtion of drugs
the transfer of a drug from its site of administration to
blood streem
the rate and the efficiency of absorbtion depend on the route of administration so in
I.V : Complete absorbtion
Other routes : partial absorbtion which lowers the bioavailability
A- Transport of drugs from GIT
depending on their chemical properities drugs may be absorbed from GIT by
Passive diffusion
Active transport
B- physical factors influencing absorbtion
blood flow to the absorbtion site
total surface area available for absorbtion
contact time at the absorbtion surface
III-Bioavailability
the fraction of administerd drug that reaches the systemic circulation in a chemically unchanged form
ex : if 100 mg of the drug is administrated orally and 70 mg of this drug is absorbed unchanged ..the bioavailability is 70%
Factors that influence bioavailability
first pass hepatic metabolism
solubility of the drug
chemical instability
the nature of the drug formulation
IV-Drug distribution
the process by which a drug reversibly leaves the blood stream and enters the interstitium (extracellular fluid) and/or the cells of tissues
Factors affect drug distribution
A- blood flow
B- capillary permeability which determined by
Capillary structure
ex : blood brain barrier : lipid soluble drugs readily penetrate to the CNS since they can dissolve in the membrane of its endothelial cells but ionized or polar drugs generally fail to enter the CNS
Drug structure
Binding of drugs to proteins
reversible binding to plasma proteins sequesters drugs in a non diffusible form and slows their transfer out of the vascular compartment
V-Binding of drugs to plasma proteins
Usually albumin
bound drugs are pharmacologically inactive ...only the free unbound drug can act on target sites in the tissues and elicit a biological response
so hypoalbunemia may alter the level of free drug
A- Binding capacity of albumin
binding of drugs to albumin is reversible
albumin may show
Low capacity : one drug molecule per albumin molecule
High capacity : a number of drug molecules per single albumin molecule
albumin has the strongest affinity for anionic drugs(weak acids) and hydrophobic drugs
most hydrophilic drugs and neutral drugs do not bind to albumin
many of drugs are hydrophobic by design since this property permits absorbtion after oral administration
B- Competition for binding between drugs & clinical imprtance of drug displacement
ex : Tolbutamide is normally 95% bound and only 5% free so 95% is inert in its pharmacological action
sulfonamid with higher affinity for albumin if adminiserd it displaces tolbutamide and now 100% of tolbutamide become free in plasma
but note that.... the tolbutamide concentration does not remain elevated since the drug moves out of the plasma into the interstitial fluid and avhievs new equilibrium
VI- Drug metabolism
drugs are most often eleminated by biotransformation and/or excretion into the urine or bile
The liver is the major site for drug metabolism
Specific drugs may undergo biotransformation in other tissues
some agents are initially administerd as inactive compounds(prodrugs) and must be metabolized to thir active forms
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