Pharmacology Lecture 2

2

Routes of Drug Administration ,Cont.
&
General Pharmacology


In the last lecture Dr.Khalil Maki started to discuss the routs oI drugs
administration .He talked about the main routs which are enteral and parenteral
.Then he discussed the advantages and the disadvantages oI the oral route as an
example oI the enteral routes oI administration .

In this lecture we will discuss the rest oI the enteral & the parenteral routs oI
administration .

The Enteral Routes (through the GIT ):
ral route .
2ucal or sublingual : it`s a pharmacological route oI administration
where the drug should be put under the tongue and leIt Ior a while ,then it
will diIIuse to the blood circulation through the buccal mucosa .

In this rout oI administration patients should be asked not to swallow their
saliva ;because iI they did the method will be converted to be an oral rout
where the drug will be absorbed in the GI not in the buccal mucosa .

dvantages oI sublingual rout :
There is NO Iirst pass eIIect .
This means that sublingual medications do not pass to the liver and the portal
circulation , because the drug will be absorbed directly to the systemic
circulation by the oral saliva and the buccal mucosa. In the other hand ,the oral
medications will be metabolized during their passage in the GI by the GIT
mucosa and then goes to the liver by the portal circulation, aIter this Iirst pass
eIIect a small amount oI the drug will reach the systemic circulation .











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2 Rapid bsorption and eIIect ; a common example oI drugs that is given by
sublingual route is Nitroglycerine which used Ior Angina Pectoris ( don`t
worry about the drugs names ).

3 Drug Stability :drugs inside the mouth will not be exposed to the digestive
enzymes that are present in the stomach or in the intestine , so the drugs will
be more stable iI compared to the swallowing method .

In the other hand , there are some disadvantages oI the sublingual rout :

Inconvenient : To some patients this route oI administration is
considered inconvenient . When compared to the oral route the only advice
that you should give to your patient is to take the pill in a setting position
with a glass oI water; where in the sublingual route you should tell your
patient not to swallow his saliva Ior one minute or more than that to
guarantee a good absorption Ior the sublingual dose.

2 Small doses only : usually sublingual medications contain smaller doses
than the oral route ,which may considered a limitation Ior this route to be
applied to a wider ranges oI medications.


3Rectal Rout : Drugs can be administered rectally in the Iorm oI
suppository ( .-~'=) or enema ( -=~ -=) .



Advantages of this method :

1ust for clarification :

) is a pass metabolism - first (also known as pass effect - first The
entration oI the drug phenomenon oI drug metabolism whereby the conc
is greatly reduced beIore it reaches the systemic circulation .
Iter a drug is swallowed, it is absorbed by the digestive system and
so , drug enters the hepatic portal system. The liver metabolize many
l amount oI active drug emerges Irom the liver to sometimes only a smal
through the liver thus Iirst pass his the rest oI the circulatory system . T
greatly reduces the bioavailability oI the drug. lternative rout oI
suppositories , intravenous ,intramuscular and administration like
pass eIIect because they allow drugs to be void the Iirst a sublingual
. absorbed directly into the circulatory system
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- Reduced (or bypass '=- ) Iirst pass eIIect, not like the oral method where
their is a huge contribution oI the Iirst pass eIIect on the bioavailability oI the
administered dose .lthough part oI the dose that is administered rectally can
be aIIected by the Iirst pass eIIect ,that`s because the rectal mucosa is drained
sometimes by the venous circulation which maniIest through the portal
circulation .

Oral rout First pass eIIect
Sublingual No Iirst pass eIIect
Rectal Reduced Iirst pass eIIect

2 UseIul in patients unable to take the drug orally such as comatosed patients
(unconscious ),or Ior children below 5 years old who are unable to take drugs
orally .

Disadvantages :
Erratic (unpredictable ) absorption : s the presence oI Ieces sometimes in
the rectum will prevent complete absorption oI the drug.

2 Not well accepted by most patients.



Parentral routes (away Irom the GIT) which divided into :

Injection : "considered one oI the main routes oI administration oI
parenteral routes " ,under this type oI administration many types oI
injections are listed ; such as :
Intravenous injection ( I V ) ~-' -='
Intramuscular ( IM) .-' -='
Subcutaneous injection ( SC ) ~=' = -='
Intraarticular injection (I) .--~' -='
Intrathecal injection (IT) ~' _'=-' .-'~ -='
intra dermal injection (ID) ' -=' ~

*** The commonly used methods are :

a ntravenous administration : it could be bolous or inIusion .

olous : the drug is taken Irom the ampule or the vial with a syringe and
injected directly to a suitable vein .
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Ampules vials

nfusion : the drug is taken Irom the ampule or the vial and not given directly
to the vein.First it's diluted in IV saline ,or dextrose water ,normal saline or
glucose saline ,then the diluted Iluid given through an inIusion set into the
suitable vein .

The method is called drip method ,which is named by the process in which the
medication is administered drop by drop . The numbers oI drops can be
regulated by a valve ; iI you Iully open it the number oI drops will be increased,
and iI the valve is tightened the number oI drops will decrease .

Advantages of this method
Rapid : no need Ior time oI absorption ;the drug will go directly to
the blood ,so the Iastest method oI drug administration is ntravenous
method.

2 Total dose and large doses will reach the circulation directly ,so iI a
drug is given intravenously the whole amount oI drug will reach the
systemic circulation .(everything will be absorbed ) .

3 suitable Ior irritant drugs ;those drugs which known to be highly
irritant to the GI tract and contributed with high rates oI nausea and
vomiting can be given easily by the intravenous route.

Disadvantages of this method :
diIIiculty in Iinding suitable vein ,specially in obese people.

2 Need an expert .e.g. doctor ,nurse not like oral ,sublingual or rectal
routes oI administration .
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3 High risk oI toxicity :due to rapid onset oI action oI some drugs .Compared
to other routes oI administration iI a patient experienced a harmIul side eIIect
Irom a medication that is given sublingually simply you can ask the patient to
spit the drug .II it was an oral medication we can induce vomiting to get rid oI
the ingested drug, also iI the drug that caused the toxicity was given rectally
you can give the patient rectal enema to get out the rectally administered drug
. But in the intravenous route oI administration you can't recall the drug that
reached the systemic circulation .

4 More expensive than other type oI drugs because it needs sterilization oI
the injected drug and sterilization oI the injection area ,also as we mentioned
earlier we need an expert to administer IV medications.


b-Subcutaneous route ( under the skin ): the drug is taken by a syringe Irom
a container and injected not into a vein but under the skin .

Advantages of this method :
SelI administration :it could be administered easily by the patient , a
common example is nsulin which is a drug Ior type diabetes where
there is no need Ior an expert .

2 Complete but a slower rate oI absorption ( intermediate compared to
orally and intravenously administered drugs ) .

3 The absorption oI a drug could be delayed by mixing the drug with a
vasoconstrictor in order to prolong the drug action by reducing the
absorption rate ( the drug will be absorbed slowly and produce its eIIect
over a long period) .The use oI a vasoconstrictor is very useIul in your
Iuture Dental practice as no dental procedure can be done without giving
the patient a local anesthetic ,but when we add a vasoconstrictor to the
anesthetic the blood vessel will be narrow which will aIIect the
absorption and thus prolonging the drug action .

Disadvantages oI this method :
PainIul
2 Irritate the injected area .
3 Only small doses can be given subcutaneously compared to orally
and rectally administered drugs. e.g. 3 ml maximum can be given
subcutaneously ,but intravenously we can give up to 2 liters oI injection
Iluid .


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c-ntramuscular method (inside the muscles ):

%he Advantages of this method :
larger volume than subcutaneous , usually we choose buttock
muscle to inject this type oI injection speciIically gluteus maximums
muscle.

II we divide the body into Iour quadrants (upper lateral ,lower lateral ,
upper medial ,lower medial) the suitable area Ior intramuscular is the
upper lateral ,and that's to avoid causing injury to the nerves which are
emerge Irom the vertebral column .

2 Depot ( =~ ) or sustained release preparation are possible: large
amount can be stored in the muscle and it can be released slowly . II we
need a drug to be released slowly to the body Ior example 3 months
,intramuscularly method is the preIerred route oI administration.

Disadvantages of this method :
PainIul method ( more painIul than the subcutaneous method )
2 Need an expert
3 Erratic absorption specially when using this method Ior Phenytoin &
Diazepam ( Don`t care about these names Ior now because we will talk
about them in the systemic pharmacology in more details ).



nhalation : examples oI drugs that are used to be administered by
inhalation route to treat bronchial asthma ( steroid , cortisone ,sympathic
amine or a bronchodilator ).

For the treatment oI bronchial asthma patients there are two options
, either giving patients their medications through systemic routs like
intravenously or orally or by giving medications through inhalation .In
the systemic routes most oI the drug will go to the circulation and the
bronchial tissue will receive a small dose oI it, so in this situation giving
patients larger doses oI medication is recommended to produce a
therapeutic eIIect .On the other hand, iI the medication is given by
inhalation method the whole amount oI drug will get directly to the
bronchioles with a minimum amount will be absorbed to the circulation ,
so we can give a very small amount through inhalation despite that it will
produce a large eIIect compared to IV or oral method .
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Giving a large amount oI any drug by inhalation will produce large local
eIIect with a minimal general eIIect to the body ,Ior example ,
bronchodilators belong to the sympathetic group oI drugs ; in general this
group oI medication aIIect :
Bronchioles bronchodilatation
Heart can cause tachycardia
Blood vessels increasing the blood pressure

These eIIects are predicted iI the drug was given intravenously but the only
needed eIIect oI such medication is bronchdilatation; we don`t need
tachycardia or hypertension ,so we preIer to give bronchodilators by
inhalation .

Inhalation route can be used to target local eIIect such as bronchodilators
and also it can produce a systemic eIIect like in general anesthetics (most
eIIective).

%he Advantages of this method :
Rapid
2 No Iirst pass eIIect because they don`t pass through the portal
circulation ,and through the liver beIore reaching the blood , they will
aIIect the bronchi and minimal amount will be absorbed to the circulation .

%he Disadvantages of this method ::
Irritation
2 Some particles may be participated in the mouth or throat .( it will be
discussed later ).



%opical ( local ) : Examples ;eye drops , gargle(==) (which we will
be used oIten in our dental practice) ,antiseptic ,sun screen ointment ( -~)
(protect Irom the sun ), cream, lotion .

Some oI the topically applied drugs have Systemic eIIect such as
Nitroglycerin ointment or patches .
When the drug is applied topically there will be high local
concentration and eIIect with minimal systemic concentration and eIIect .

Keep in mind that absorption oI topically applied drugs could be increased
where there is an injury or cut or abrasion to skin .Be careIul when you
apply drugs topically to inIants because they have a very thin skin and the
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a mount oI drug will be rapidly absorbed ,which will lead easily to toxic
maniIestations .

By this we Iinish the rout oI drug administration .


Chapter 2 :General Pharmacology

In the last lecture the Dr deIined Pharmacology as the science that
deals with drugs, where Drugs are deIined as any chemical substances that
are used Ior treatment ,prevention and diagnoses .


Pharmacology is divided into two main branches :

Pharmacokinetics : it is what the body does to the drug .The body will absorb
the drug ,aIter that the drug will reach the site oI action in a distribution process
and Iinally produce its eIIect .
useIul drug doesn't just get absorbed ,distributed ,and produced its eIIect,
otherwise it should be removed Irom the body . The drug is removed Irom the
body in a process called Metabolism ,some drugs will be metabolized beIore
their excretion outside the body but others could be only eliminated or excreted
unmetabolized (without metabolism ).

The Pharmacokinetic processes are : Absorption ,Distribution ,Metabolism
,Elimination /Excretion ( ADME )

2 Pharmacodynamic: ( the opposite ) it is what the drug does to the body ,it
deals with the pharmacological action and the mechanism oI their actions .
Simply Pharmacodynamic is the mechanism oI action .

Now ,we will talk in Iurther details about the Pharmacokinetics Processes :

) Absorption : The passage oI drugs Irom the site oI administration
(Irom outside ) to the systemic circulation.

"Sublingual absorption": is the passage oI the drug Irom the saliva through the
buccal mucous membrane to the buccal blood supply .

For a drug to be absorbed , it should pass through a cell membrane . drug
which is absorbed sublingually has to pass through the buccal mucosa then
through the endothelium lining oI the capillary. The same by intramuscular
administration ,the drug is injected into the extra vascular space and the only

membrane that should be passed is the endothelium lining oI the blood
capillary .However ;in intravenous administration there is no absorption
because the drug goes directly into the blood where there is no membrane
barrier that should be passed .

The cell membrane is mainly composed oI lipid bilayer ,so Ior a drug to pass
through the membrane it should be "lipid soluble" ( Lipophilic or hydrophobic
) other than intravenous route .

***Highly water soluble drugs are not absorbed .
***Highly lipid soluble drugs are highly absorbed .

Drugs are present in two Iorm :
Ionized Iorm ;which is highly ater soluble not absorbable.
2 Nonionized Iorm (molecules);which is highly lipid soluble more
absorbable .

So, what determines the rate oI the drug absorption ?
Lipid solubility Directly proportional
2 Water solubility Indirectly proportional

*** The percent oI lipid / water or water / lipid solubility is called degree oI
ionization .

***The higher the degree oI absorption the loer the degree oI ionization
indirectly proportional .

***The higher the degree oI ionization the higher the number oI ions and
lower the absorption .

What determines the degree oI ionization is the PH and the PKa;
ccording to asselbach- anderson Equation

cidic drugs PKa PH log M/I

Basic drugs Pkb PH log I/M

M : Molecular
I : Ionic

Example : spirin is an acidic drug ,has a Pka 3.4 ,while the PH oI the
stomach .4 so :


PKa PH log M/I
3.4 .4 log M/I
log M/I 2
M I

*** That's mean that spirin in the stomach is mainly non ionic (molecular
Iorm), which could absorbed easily .

How the aspirin behave in the duodenum ?

The PH in the duodenum 7.4
PKa PH log M/I
3.4 7.4 Log M/ I
log M/I 4
I M

So spirin will be highly ionic in the duodenum, thus a little absorption will
happen. However; the aspirin is mainly absorbed in the intestine because oI
the wide surIace area oI the intestinal mucosa .



%he End

Done y : Enas Salameh


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