kinetics of drug elimination

kinetics of drug elimination

 

-Plasma clearance

it is the volume of plasma from which all drug appears to be removed in a given time.
clearance = rate of elimination (Roe) \C

-extraction ratio = C2/C1.

C1 is concentration of drug enters the kidney
C2 is concentration of drug exits the kidney

-Excretion rate =clearance * plasma concentration

        mg/min          ml/min               mg/ml

Total body clearance

The total body (systemic) clearance, CLtotal or CLt, is the sum of the clearances from the various drug-metabolizing
and drug-eliminating organs.

CLt = CL hepatic   +    CL renal    +   CL pulmonary   +   CL other

CLt  can be derived from the steady-state equation:

CLt = ke Vd
where ke = the first-order rate constant for drug elimination from the total body.
           Vd  is the volume of distribution

-half-life time  t½

 t½ =0.693Vd/CL
 This is the period of time required for the concentration or amount of drug in the body to be reduced by one-half.
it depends on how quickly the drug is eliminated from the plasma.

drugs that are cleared from the blood more rapidly than others need to be given in regular doses to build up and maintain a high enough concentration in the blood to be therapeutically effective.
as repeated doses of a drug are administered its plasma concentration builds up and reaches what is known as a steady state. This is when the amount of drug in the plasma has built up to a concentration level that is therapeutically effective and as long as regular doses are administered to balance the amount of drug being cleared the drug will continue to be active. The time taken to reach the steady state is about five times the half life of a drug.
(a steady-state is achieved when the plasma concentration of drug remains constant)
Roe =CLt)(C)
Css ( the steady-state concentration) =Ro /keVd = RoCLt     

Ro      is the infusion rate
ke     is the first-order elimination rate constant
Vd      is the volume of distribution (constant for most drugs )

 i hate  equations :(

Drug elimination

 Drug elimination

Drugs are cleared primarily by the liver and kidneys. Excretion into the urine is a major route of elimination for metabolites and unchanged drug.


organs that excrete drugs eliminate water soluble  .

Lipid soluble drugs are not readily eliminated until they are metabolized to more polar compounds.

Possible sources of excretion include:

Breath -Urine -Saliva -Perspiration -Feces -Milk -Bile-Hair.

- kidney is the most important organ that eliminate drugs and their metabolites.

-Substances excreted in the feces are the orally ingested unabsorbed drugs or metabolites excreted in the bile that are not reabsorbed from the intestinal tract.

- Pulmonary excretion  is important as it pertains to the elimination of anesthetic gases and vapors, as well as alcohol.

 

 A. Renal elimination of a drug

1- Glomerular filtration:

Drugs enter the kidney through renal arteries, which divide to form a glomerular capillary plexus.
 no bound to albumin drugs flows through the capillary slits into Bowman's space as part of the glomerular filtrate . 
The glomerular filtration rate (125mL/min) is normally about twenty percent of the renal plasma flow (600 mL/min). 
(it is not affected by PH and lipid solubility.)

 

2- Proximal tubular secretion:

Drugs that were not transferred into the glomerular filtrate leave the glomeruli through efferent arterioles,
 which divide to form a capillary plexus surrounding the nephric lumen in the proximal tubule. 
Secretion primarily occurs in the proximal tubules by two energy-requiring active transport (carrier-requiring) systems, one for anions
 (for example, deprotonated forms of weak acids) 
and one for cations
(for example, protonated forms of weak bases). Each of these transport systems shows low specificity and can
transport many compounds; thus, competition between drugs for these carriers can occur within each transport
system . [Note: Premature infants and neonates have an incompletely developed tubular secretory mechanism and, thus, may retain certain drugs in the glomerular filtrate.]

3-Distal tubular reabsorption:

drug concentration increases when it  moves toward the distal convoluted tubule, and exceeds that of the perivascular space.
  if The drug is uncharged, may diffuse out of the nephric lumen, back into the systemic circulation. to minimize the amount of back-diffusion, increasing the ionized form of the drug in the lumen may be used , and hence, increase the clearance of an undesirable drug. As a general rule, weak acids can be eliminated by alkalinization of the urine, whereas elimination of weak bases may be increased by acidification of the urine.

4- Role of drug metabolism:

 Most drugs are lipid soluble and without chemical modification would diffuse out of the kidney's tubular lumen when the drug concentration in the filtrate becomes greater than that in the perivascular space. 
To minimize this reabsorption, drugs are modified primarily in the liver into more polar substances using two types of reactions:

- Phase I reactions.

  that involve either the addition of:-
hydroxyl groups( or) the removal of blocking groups from hydroxyl, carboxyl, (or) amino groups.
 
and

 -Phase II reactions .

 that use conjugation with sulfate, glycine,( or) glucuronic acid to increase drug polarity.
 The conjugates are ionized, and the charged molecules cannot back-diffuse out of the kidney lumen.

Drug Metabolism

Drug Metabolism

 Drug metabolism is transforming drugs, so they can be excreted from the body. They can interact with other drugs and foods, . Interactions can lessen or magnify the desired therapeutic effect of a drug, or may cause unwanted  side effects. There are thousands of possible drug-to-drug and drug-to-food interactions, and many medications and supplements are contraindicated  under certain conditions or in patients with specific diseases and disorders. This is why it is important that patients told their physician fully informed about all drugs and dietary supplements including herbal remedies they are taking.
Most drugs are treated by the body like foreign substances, also known as xenobiotics. Humans have evolved a complex system for xenobiotic metabolism. It is thought that exposure to the many toxic compounds in plants has facilitated the development of enzyme systems to detoxify foreign substances. Occasionally, though, the enzymes make an intermediate more toxic than the parent compound. This can happen with some of the compounds in cigarette smoke.
The metabolism of drug depend on many factors
 Physiological factors
AGE
in neonates & infants ==>LMEs (liver microbial enzymes) are immature meaning not well-developed
in geriatric ==>LMEs are impaired meaning their activity decrease
SO we can say that we must adjust drug dose for pediatrics & geriatrics carefully
sex
males have higher activity of LMEs than females WHY
because male sex hormones are microsomal enzyme inducers but female  sex hormones are microsomal enzyme inhibitors.

NUTRITION

malnutrition decreases activity of LME

Genetic factors
due to species & individual differences

Environmental factors
STRESS
leads to increased metabolism HOW
stress increases blood level of glucocorticoids which are LME inducers
FOREIGN COMPOUNDS
as insecticides & preservatives ==> LME inducers
DRUGS
  some drugs are LME inhibitors but most drugs are LME inducers.

Drug metabolism usually consists of two phases.

 Phase 1 

non synthetic reactions
for all types of drugs
involve metabolic modifications which may give more active compounds than original
EX
Oxidation : methyl alc. is oxidized to formic acid==> toxic
phenacetin is oxidized to paracetamol
tremorine is oxidized to oxotremorine==>tremor inducing drug
Reduction : trichloroethanol is reduced to chloral hydrate
Hydrolysis : Acetyl salicylate is hydrolyzed to acetate & salicylate

Phase 2

 synthetic reactions
for only some drugs
involve conjugation to give water sol. subs. easily to be excreted
Conjugation is done with glucoronic acid (mainly) ,acetic acid ,glycine ,or sulphate
Ex
Benzoic acid + Glycine =====> Hippuric acid

 

Drug Distribution

Drug Distribution

 It is the process by which the drug  reversibly leaves the bloodstream and enters tissues.

it depends on:-

1- capillary permeability

determined by capillary structure and chemical nature of the drug.
-The capillary wall consists of an endothelial cell layer and abasement membrane enveloping the endothelial cell layer .Capillary structure varies widely in terms of the basement membrane that is exposed by slit (tight) junction between endothelial cells In the brain, the capillary structure is continuous, and there are no slit junctions The capillaries of the brain are surrounded by a thick lipid membrane. Polar and ionic hydrophilic drugs cross this barrier slowly In order to enter the brain, drugs must be actively transported through the endothelial cell so repass through the endothelial cells of the capillaries of the central nervous system (brainand spinal cord).
Ionized or polar drugs generally fail to enter the CNS, since they are unable to pass through the endothelial cells of the CNS.
-drug  structure
The chemical nature of the drug strongly influences its ability to cross cell membranes. Hydrophobic drugs (lipophilic drugs),readily move across most biological membranes. The major factor influencing the hydrophobic drug's distribution is the blood flow to the area. By contrast, hydrophilic drugs, do not readily penetrate cell membranes and must go through the junctions of endothelial cells in capillary beds .Small drug molecules can freely diffuse out of the blood vessel while large drug molecules are confined to the plasma

2- blood flow

The rate of blood flow to the tissue capillaries varies widely as a result of the unequal distribution of cardiac output to the various organs.

3- the degree of binding of the drug to plasma proteins

Albumin is the major drug-binding and may act as a drug reservoir , when the drug eliminated by metabolism or excretion the bound drug dissociate from protein.

-volume of distribution

The volume of distribution is  is the ratio of the amount of a drug in the body to its concentration in the plasma or blood.
                                          Amount of drug in the body (Q)
  volume of distribution (Vd)=  ------------------------------
                                           Plasma drug concentration(C)
-large molecular weigh drug or extensively bind to plasma proteins drugs are too large to pass through capillaries and trapped within the plasma . in this case the drug distributes in plasma which is about 6% of the body weight ( 4L in 70 kg individual )
-low molecular weight & hydrophilic can move through capillaries slit junctions into interstitial fluid
however hydrophilic cannot pass through the lipid cell membrane to enter the water phase of the cell so this drugs  distribute in the volume  ( plasma water + interstitial fluid) (extracellular fluid ) about 20 % of the body weight ( 14 L in 70 kg individual)
-low molecular weight & hydrophobic can move through the endothelial slit junction into interstisial fluid and can pass through the cell membrane into the intracellular fluid the drug, therefore, distribute in the total body water about 60% of body weight (42L in 70kg individual)
-in pregnancy extremely lipid soluble drug  distribute to placenta and thus increase Vd .
sometimes drug(2) can take the place of drug(1)that binds to the plasma proteins so the concentration of drug 1 will increase and may reach the toxic concentration .
-ex:-
1-Chloral hydrate ,clofibrate ,phenybutazone can displace coumarin which is anticoagulant so if we take any drug of this  3 drugs with Coumarin it will cause bleeding.
2-Salicylates can displace Tolbutamide which is a hypoglycemic drug so Hypoglycemic shock will happen if we take both drugs with each other.
-drugs of high Vd have high half-life .

4- the degree of binding of the drug to tissue proteins.

some drugs prefer to accumulate in specific tissues for ex:-
Chlorpromazine prefer Brain
Digitoxin prefer Liver ,Kidney & Heart
Tetracycline prefer Bones & Teeth
Calcium prefer Collagen
Arsenic prefer Keratin
Iodine prefer Thyroid gland .... and so on

5- hydrophobicity of the drug. 

 

translation into Arabic

Drug Distribution

انتشار الدواء و بيعرف على انه عملية انتشار الدواء من الدم الى الخلايا و العكس والعملية دى بتعتمد على

1- capillary permeability

ودى فيها نقطتين اول نقطة تركيب الشعيرة الدموىة وتانى نقطة اللطبيعه الكيميائية للدواء

الشعيرة بيبقى فيها basement membrane  محاط بطبقة من indothelial cell   الطبقة دى بيبقى فيها فتحات اسمها slit junctions  فبالتالى بيبقى فى جزء من ال basement membrane  ظاهر(الجزء الظاهر ده بيختلف من شعيرة دموية لشعيرة أخرى حسب مكان وجودها فى الجسم )المهم ان الجزء الظاهر ده هو اللى بيمر منه الplasma proteins ،  لكن فال brain  مفيش slit junctions  وفى طبقة سميكة من الدهون فبالتالى lipid drugs هتمر لل brain لكن ال charged drugs  مش هتعرف تمر ولازم تدخل على  carriers بال Active transport   

تانى عامل بيأثر على الانتشار هو

2- blood flow لانه بيختلف من مكان لمكان لان ال Cardiac output  بيختلف من عضو لعضو يعنى مثلا بيبقى كتير للكبد والكلية و المخ لكن بيبقى قليل للخلايا الدهنيه والجلد وهكذا.

تالت عامل بقى هو درجة ارتباط الدواء ببروتينات الدم

3- the degree of binding of the drug to plasma proteins

الالبيومين هو اكتر بروتين بترتبط بيه الادوية لدرجة انه ممكن يكون مخزن للدواء ( لما كمية الدواء الغير مرتبطة ببروتينات تقل بسبب تكسيره فالكبد او اخراجه يروح الالبيومين مطلع شوية

هنتكلم بقى دلوقت عن حاجه اسمها

-volume of distribution

وهو عبارة عن النسبه بين كمية الدواء اللى دخلت جسمنا وتركيز الدواء اللى وصل للبلازما وبتتحسب بالمعادلة دى

                                         ( Amount of drug in the body ( Q

                                               ------------------------------     =  volume of distribution Vd

                                         (  Plasma drug concentration ( C

large molecular weight drugs-  بترتبط ببروتينات البلازما وبالتالى بتنتشر فالبلازما بس اللى هى حوالى 6% من وزن الجسم يعنى  4 ليتر فى شخص وزنه 70 كيلو

low molecular weight  hydrophilic drugs-  بتقدر تعدى من ال slit gunction وتوصل لل extracellular fluid لكن مش بتقدر توصل لل  intracellular fluid وبالتالى بتنتشر فى حجم ( البلازما + السوائل اللى خارج الخلية )

بيكون تقريبا 20 % من وزن الجسم يعنى 14 ليتر فى شخص وزنه 70 كيلو

low molecular weight  hydrophobic drugs- بتقدر تعدى وتدخل جوة الخلية يبقى هتكون منتشرة فالبلازما والسوائل خارج الخلية والسوائل داخل الخلية (كل سوائل الجسم )يعنى تقريبا 60 % من وزن الجسم تقريبا 42 ليتر فى شخص وزنه 70 كيلو

- فى الحوامل ال Vd بيزيد فى حالة الادوية اللى هى extremely lipid soluble  لانه بينتشر وبيوصل الplacenta  .

-فى بعض الاحيان بيبقى عندنا دواء مثلا (2) بيبقى مرتبط ببروتينات البلازما وناخد دواء  تانى هنسميه (1) ييجى بقى الدواء  رقم(1 ) ياخد مكان الدواء (2) على البروتين ويخلى الدواء (1) حر فالدم وبالتالى تركيزه هيزيد وممكن يوصل لل toxic concentration

طيب نشوف أمثله على كده

1-Chloral hydrate ,clofibrate ,phenybutazone can displace coumarin which is anticoagulant

,وبالتالى لو خدنا اى دواء من التلاته دول مع الcoumarin  هيحصل نزيف.

2-Salicylates can displace Tolbutamide which is a hypoglycemic drug  يعنى هيحصل غيبوبة سكر لو خدنا النوعين دول مع بعض

- لما بيكون  Vd  كبيرة بيبقى الhalf-life بتاعة الدواء عاليه واى عامل بيزود ال Vd  اكيد هيزود ال half-life بتاعة الدواء.

4- the degree of binding of the drug to tissue proteins.

رابع عامل بيأثر على انتشار الدواء هو درجة ارتباط الدواء ببروتينات الخلية لان بعض الادوية بتفضل تتجمع فى بعض الخلايا مثلا

Chlorpromazine prefer Brain

Digitoxin prefer Liver ,Kidney & Heart

Tetracycline prefer Bones & Teeth

Calcium prefer Collagen

Arsenic prefer Keratin

Iodine prefer Thyroid gland .... and so on

خامس حاجه بقى بتأثر على الانتشار هى

5- hydrophobicity of the or drug  structure

Hydrophobic drugs (lipophilic drugs) بتقدر تمر من اى جدار وتدخل جوة الخلية لكن ده  بيعتمد على ال blood flow  لمنطقة الانتشار

لكن hydrophilic drugs مش بتقدر تدوب فى جدار الخلية الدهنى عشان تدخل الخلية ، لكن ممكن تمر من ال slit junctions  .

 

Bioavailability

Bioavailability

It is the amount of the drug that reach the systemic circulation in chemically unchanged form .
it is determined by comparing plasma levels of drug after a particular route of administration with plasma drug levels achieved by IV injection.

-Factors affecting bioavailability

1.First pass hepatic metabolism

as in oral route amount of the drug is metabolized by liver before reaching systemic circulation .

2. solubility of the drug

very hydrophobic and very hydrophilic drugs are poorly absorbed ,the drug must have some solubility in aqueous solutions  to reach the surface of cells.

3. chemical instability

some drugs are unstable in GIT PH (ex. penicillin G ).
other drugs are destroyed by enzymes of GIT ( ex. Insulin ).

4. Nature of drug formulation

as particle size, enteric coating, salt form and excipients .

- Bioequivalence

2 drugs are bioequivalent if they show comparable bioavailability and similar time to achieve peak blood concentration . 2 drugs withe significant diffference in bioavailiability are bioinequivalent.

-therapeutic equivalence

2 similar drugs of comparable efficacy and safety are therapeutically equivalent.
2 drugs that are bioequivalent may not be therapeutically equivalent.

translation into Arabic
 
بسم الله الرحمن الرحيم
هنتكلم النهارده عن حاجة اسمها
Bioavailability
وبنعرفها على انها كمية الدواء اللى بتوصل للدم من غير اى تغيير كيميائى وعشان نقيسوها بنرسم curve
المحور (ص) بنسجل عليه تركيز الدواء فالبلازما والمحور ( س) بنسجل عليه الوقت من بداية تناول الدواء
وبنقدر نحسبها من خلال المعادلة دى
Bioavailability = (AUC oral\AUC injected) * 100

ايه هى بقى العوامل اللى بتأثر على ال Bioavailability
-Factors affecting bioavailability
1.First pass hepatic metabolism
يعنى مثلا احنا لما بناخد الدواء عن طريق الفم قولنا انه بيحصله تكسير فالكبد قبل ميحصله امتصاص وبالتالى ال Bioavailability هتقل
2. solubility of the drug
لما الدواء يكون extremely hydrophobic هيبقى امتصاصه قليل جدا لانه مش هيدوب فى سوائل الجسم ، ولو كان very hydrophilic هيبقى امتصاصه قليل جدا برضه لانه مش هيمر من خلال الغشاء الدهنى للخلية
لكن عشان الدواء يحصله امتصاص يفضل انه يكون hydrophobic لكن بيدوب شوية فالماء
3. chemical instability
بعض الادوية بتبقى غير مستقرة فى الوسط الحامضى بتاع المعدة زى ex. penicillin G
وبعض الادوية بتتكسر بالانزيمات ex Insulin
4. Nature of drug formulation
as particle size, enteric coating, salt form and excipients .
------------------------------------------------------------------------
- Bioequivalence
امتى نقول على نوعين من الادويه انهم Bioequivalent
لما يكون لهم Bioavailability متقاربه وبيستغرقوا نفس الوقت عشان يوصلوا peak blood concentration
لكن لو مختلفيين فى ال Bioavailabilityبنقول عليهم bioinequivalent

-therapeutic equivalence
امتى نقول على نوعين من الادوية انهم therapeutically equivalent لما يكونوا متقاربين فى الفاعليه والأمان
ولو عندين نوعين من الدواء bioequivalent مش شرط يكونوا therapeutically equivalent.

Drug Absorption

Drug Absorption

 It is the transfer of drug from site of administration to blood , it's depend on

- the rout of administration
- PH
- physical factors

A- the effect of route of Administration

- absorption is complete in case of IV delivery because the total drug reach blood
-absorption is partial in other routes of administration so the bioavailability is decreased ( ex, in oral route the drug dissolve in GI fluid so the presence of food may affect this process ) .
-drug absorption from GIT depend on chemical properties of the drug .
-drug absorbed from GIT by:-

1. passive diffusion

drug moves from region of high concentration to one of lower concentration without a carrier .
it does not require energy.
lipid-soluble drugs pass across membrane due to their solubility in the membranes (lipid)
water-soluble drugs penetrate cell membrane through aqueous channels or pores

2. Facilitated diffusion

drug moves from region of high concentration to one of lower concentration by a carrier proteins .
it does not require energy

3. Active transport

drug need a carrier and energy to move from low concentration to high concentration (against concentration gradient)
it is driven by the hydrolysis of adenosine triphosphate.

4.Pincoctosis 

it is engulfment of drug molecule ( large size drug molecules ) by the cell membrane and transport into cell by pinching off the drug-filled vesicle.

B- Effect of PH on drug absorption

most drugs are weak acids or weak basic
 acidic drug (HA) (uncharged) release H positive and A negative (charged)
basic drug (HB positive) (charged) release H positive and  B (uncharged)
uncharged drug are more readily passes through membrane
so:-
uncharged weak acid (HA) pass while charged (A negative ) cannot
charged weak base (HB positive) cannot pass while uncharged (B) pass.

C- physical factors affecting absorption

1- blood flow to absorption site

the greatest the blood flow the greatest the absorption

2- total surface area available for absorption

the largest the surface area the largest the absorption

3- contact time at the absorption surface

if drug moves quickly in GIT drug will not be well absorbed
if transport of drug from stomach to intestine delayed absorption will delayed
if drug taken with meal the food will  dilute drug and slow gastric emptying causing slow absorption.

translation into Arabic
 drug absorption
امتصاص الدواء
ودى اول عمليه من عمليات pharmacokinetics
وهو عبارة عن انتقال الدواء من مكان تناوله للدم
فى عندنا بعض العوامل اللى بتأثر على عملية الامتصاص اول عامل هو:-
rout of drug administration 1
يعنى مثلا احنا لو اخدنا الدواء فالوريد هيبقى نسبة الامتصاص بتاعته 100% لكن لو اخدناه عن طريق الفم مش هيوصل كله للدم لان فيه نسبه منه بتتأثر بحامضية المعدة واللى بيتكسر فالكبد قبل الامتصاص يعنى مش بيوصل كله للدم
طيب هو الدواء ازاى اصلا بيوصل للدم ؟؟ يعنى الامتصاص ده بيحصل ازاى ؟؟عندنا 4 طرق
1-Passive diffusion
فى الطريقه دى الدواء بيتحرك من منطقة التركيز العالى للدواء ويورح لمنطقة التركيز المنخفض ومش محتاج لا طاقه ولا حامل عشان ينقله
جزيئات الدواء اللى هى lipid soluble بتمر من خلال غشاء الخلية اللى هو اصلا lipids لكن الجزيئات اللى هى water soluble بتمر من خلال aqueous channels or pores اللى موجودة فى جدار الخلية
تانى طريقه هى
2- Facilitated diffusion
الجزيئات اللى بتمر بالطريقه دى اللى بتبقى حجمها كبير وهنا الدواء يتحرك من التركيز الاعلى ويروح للتركيز الاقل زى الطريقه اللى قبله بس بيحتاج حامل يشيله لكن مش بيحتاج طاقة
تالت طريقة
3-Active transport
ودى خاصة برضه بالجزيئات الكبيرة لكن هنا الجزيئات ممكن تتحرك against concentration gradient يعنى من تركيز اقل للتكيز الاعلى وبتحتاج حامل وبتحتاج طاقة ، والطاقة دى بتنتج عنhydrolysis of adenosine triphosphate.
الطريقة الرابعه
4.Pincoctosis
وهنا جدار الخلية بيعمل زى حاوية كده ياخد فيها جزيئات الدواء وبعدين يفتح من الناحية التانيه ويخرج الدواء ودى برضه للجزيئات الكبيرة.

تانى حاجه بتاثر على الامتصاص هى :-
2-PH
معظم الادوية بتبقى يا اما weak acids or weak bases
acidic drug (HA) (uncharged) release H positive and A negative (charged) لما البروتون بيمشى بيفضل ال A السالبه الشحنه
basic drug (HB positive) (charged) release H positive and B (uncharged) لما البروتون بيمشى بتفضل ال B الغير مشحونة
uncharged drug are more readily passes through membrane
والجزيئات الغير مشحونة هى اللى بتمر يبقى الHA هيمر لكن ال A المشحونة مش هتعدى
و B المش مشحونة هتمر
لكن ال HB المشحونة مش هتمر
تالت حاجه بقى بتأثر على الامتصاص هى
3- physical factors affecting absorption
زى ايه
1- blood flow to absorption site
كل ما زاد تدفق الدم كل ما زاد الامتصاص
2- total surface area available for absorption
كل ما زادت المساحة كل مازاد الامتصاص مثال مساحة االامعاء اكبر من المعدة عشان كده الامتصاص من الامعاء اكتر منه فالمعده
3- contact time at the absorption surface
بمعنى ان لو فى مريض عنده اسهال هيحصل تفريغ للمعدة والامعاء بسرعه فبالتالى الدواء مش هيلحق يحصله امتصاص
وبرضه لو الدواء طول فالمعدة سبب الاكل مثلا برضه هيقلل الامتصاص.

routes of drug Administration

||. Routes of administration.

it is determined by:-
- The properties of the drug (water or lipid solubility , ionization , etc.) 
-Therapeutic objectives (desirability of rapid onset of action or the need for long term administration or restriction to local site) .

A. Enteral

Administration of drug by mouth (it is the most common rout)

1. Oral

Oral drugs are easily self-administered but exposing drug to gastrointestinal environments my limit its absorption.
most drugs absorbed from GIT enter the portal circulation before they distributed into general circulation
by exposing drugs to liver they may be intensively metabolized before reaching the rest of body  (drugs undergo first-pass metabolism)
ex. 90% of Nitroglycerin is cleared during passage through the liver so it never be taken orally.

2.Sublingeual

drugs defuse to the capillary network and enter systemic circulation directly.
- Advantages :-
 ease of administration - fast drug Action -Avoidance of harsh environment of GIT- avoidance of first path metabolism.

B. Parenteral (intravenous or intra-arterial - intramuscular - subcutaneous )

drugs are introduced directly into the systemic circulation
this route is used for :-
- GIT poorly absorbed drugs (ex. Heparin )
-drugs that are unstable in GIT (ex. Insulin )
used in treatment of unconscious patients .
-Advantages :-
high bioavailability -avoidance of GIT environments - avoidance of first-path metabolism - maximal degree of control over the circulating levels of the drug
-disadvantages :-
pain - fear - infections - can't be recalled by emesis or binding to activated charcoal .

1. Intravenous (IV)

the rate of infusion must be controlled to prevent adverse reactions by the too-rapid delivery of concentrations of drug to plasma and tissues.

2. Intramuscular (IM)

 drug administered by this route can be:-
-aqueous= fast absorption of drug
-suspension in nonaqueous vehicle  (depot preparations)=slow absorption

3.Subcutaneous (SC)

this route minimizes the risks of intravascular injection
ex. Insulin or solid like single rod of contraceptive etonogestrel

C- Others

1- Intranasal :- 

such as decongestants

2- Inhalation:-

( used for gases drugs and drugs that can be dispersed in aerosol )=rapid action of drug used for patients with respiratory complaints

3- Intrathecal:-

 drug is introduced directly into cerebrospinal fluid

4- Transdermal:-

 it gives systemic effect by application of the drug to the skin

5- Topical :-

 such as drops , ointments, creams ,gel , and powder it is used when  topical effect is required.

6- Rectal :-

it's useful in case of the patient is vomiting or unconscious
  it has the advantage of preventing destruction of drug by intestinal enzymes but it is often irritate rectal mucosa.
translation into Arabic
 
بسم الله الرحمن الرحيم
Routs of drug administration
يعنى طريقة تناول الدواء
طيب دى بنحددها على اساس ايه اولا
- The properties of the drug خصائص الدواء يعنى هو بيدوب فى الماية ولا بيدوب فالدهون ولا هو متأين ولا لا وهكذا
وبيعتمد كمان على -Therapeutic objectives
يعنى الغرض العلاجى هل احنا عاوزين تأثيره يبقى سريع ولا تأثير موضعى وهكذا.
احنا عندنا طريقتين اساسيتين
A. Enteral
B. Parenteral
هنتكلم الاول عن A. Enteral
وده تناول الدواء عن طريق الفم و دى اكتر طريقه بتستخدم
عندنا طريقتين
1. Oral
ميزة الطريقه دى اننا ممكن ناخد العلاج بنفسنا بسهولة لكن عيوبها ان الدواء لما يوصل المعدة ممكن يتأثر بالوسط الحمضى والامتصاص بتاعه يقل او ممكن يحصله
first-pass metabolism) يعنى الدواء بيتكسر فالكبد قبل ميحصله انتشار فالجسم ومثال على كده النيتروجليسيرين مش بيتاخد عن طريق الفم ابدا لان 90% منه بيتكسر فالكبد قبل ميحصله انتشار فالجسم
2.Sublingeual
فى الطريقه دى بنط الدواء تحت اللسان المنطقه دى فيها شعيرات دمويه كتير فالدواء بيحصله امتصاص سريع ومباشر للدم
مزايا الطريقه دى سهولة تناول الدواء بنفسك سرعة امتصاص وتأثير الدواء وتفادى عيوب الطريقه الاولى لان الدواء مش بينزل المعدة ومش بيحصله تكسير فالكبد
نتكلم دلوقتى بقى عن
B. Parenteral (intravenous or intra-arterial - intramuscular - subcutaneous )
وهنا الدواء بدخل مباشرة لل systemic circulation
والادوية اللى بتتاخد بالطريقه دى معظمها مينفعش يتعمل غير حقن لاننا لو عملناها حبوب مثلا هتبوظ لو نزلت المعدة زى النسولين مثلا بيبقى غير مستقر فالمعده او الهابارين اللى مش بيمتص غير بسيط اوى فالمعدة
والطريقه دى بتستخدم فى حالات الاغماء لان المريض مش هيعرف يبلع ادويه لانه مغمى عليه
مزاياها high bioavailability يعنى كمية الدواء اللى بتبقى فالبلازما سليمة ومن غير تكسير بتبقى عاليه جدا وطبعا سرعة تأثير الدواء دده غير انه مش بيتأثر بطبيعة المعدة ولا بيتكسر فالكبد قبل انتشاره فالجسم
عيوب الطريقه دى انها مؤلمة و ممكن تتسبب فى نقل الامراض ولو المريض اخد دواء غلط صعب تعالجه لانك مش هتقدر تخليه مثلا يرجعه او تديله تشاركول عشان يمتص الدواء ويتخلص منه
1. Intravenous (IV)
فى الطريقه دى لازم الrate اللى بتدى بيه يكون بطئ
2. Intramuscular (IM)
والادوية اللى بتعطى بالطريقه دى ممكن تكون
aqueous ودى تأثيرها سريع وبينتهى برضه بعد فترة مش طويله
او
suspension in nonaqueous vehicle
زى (depot preparations) امتصاصها بطئ و تأثير الدواء بيبقى ممتد المفعول .
3.Subcutaneous (SC)
زى الانسولين او الحاجات اللى بتتزرع تحت الجلد فى نوع مانع للحمل بيستخدم بالطريقه دى.
احنا كده خلصنا النوعين الاساسيين لكن فى طرق تانيه متنوعه زى
C- Others

such as decongestants
2- Inhalation:-زى البخاخات بتاعة ضيق التنفس وده تأثيره سريع جدا
( used for gases drugs and drugs that can be dispersed in aerosol )=rapid action of drug used for patients with respiratory complaints
3- Intrathecal:- زى البنج النصفى
drug is introduced directly into cerebrospinal fluid
4- Transdermal:- الباتشز اللى بتتلزق على الجلد
it gives systemic effect by application of the drug to the skin
5- Topical :- ده فى حالة مثلا حرق او فطريات التهاب بسيط بنسعمل كريم او مرهم او قطرة وهكذا
such as drops , ointments, creams ,gel , and powder it is used when topical effect is required.
6- Rectal :- الطريقه دى بتبقى مفيدة فى حالات الاغماء والترجيع لكن عيبها انها بتعمل irritate rectal mucosa وميزيتها انها مش بتتكسر بالانزيمات اللى فالامعاء
it's useful in case of the patient is vomiting or unconscious
it has the advantage of preventing destruction of drug by intestinal enzymes but it is often irritate rectal mucosa
7- vaginal
زى اللبوس المهبلى