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Pharmacokinetic > Elimination 

Three factors affecting elimination process are:

1) Perfusion of organ
- Refers to passage of fluid through circulatory system to an organ usually refers to delivery of blood to capillary bed.
- By increasing blood flow to the kidney increased the rate of elimination.

- For example, dopamine causes vasodilatation of renal vessels will enhance elimination.

2) Protein binding
- A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can diffuse through membrane.
- Bounded drug will not be eliminated compare to drug in unbounded form.

- For example, changes in albumin level affects phenytoin elimination.

3) Drug metabolism
- Breakdown of drug by specialized enzymes.
- Increased metabolism cause a decreased in plasma half life which eventually will enhance elimination.

- For example, donepezil is hepatically metabolized and the predominant route for both parent drug and its metabolites is renal.

Name of members
Group photo

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Pharmacokinetic > Absorption

Four factors affecting the absorption process are:

(1) Physiochemical properties
---> Molecular size
- The smaller the particle size, the greater is the effective surface area, and the more intimate contact between solid surface and aqueous solvent. Hence, higher is the dissolution rate, and an increase in absorption efficiency.

- For example, particle size reduction has been used to increase the absorption of a large number of poorly soluble drugs, such as bishydroxycoumarin, digoxin, griseofulvin, nitrofurantoin and tolbutamide.

---> Lipid water solubility
- Lipid soluble (lipophilic) drug diffuses readily across cell membranes.  High water solubility (hydrophilic) drugs have high electrical resistance and thus cannot penetrate cell membranes easily.

- For example, lipid soluble drug, such as aspirin, freely diffuse across the gastric mucosa into the circulatory system.

---> Degree of ionization
- Non ionized drug (non polar) can diffuse across the membrane as they are lipid soluble whereas ionized drug (polar drug) cannot absorb from biological membrane. Therefore,the more  the lipid soluble the drug is the more the absorption whereas the more the water soluble the drug is the less the absorption.

- Example is codeine which ionized at gastric pH, and is unionized at intestinal pH; thus better absorption from intestine.

(2) Dosage form
- Types of dosage form will directly influence disintegration and dissolution rate of a drug.

-As a general rule,the bio-availability of a drug from various dosage forms decrease in the following order: Solutions>Emulsions>Suspensions>Capsules>Tablets>Coated Tablets>Enteric coateds
Tablets>Sustained Release Products

(3) Area of use
- The absorption of a drug depends on the location it dissolves. The extent of ionisation of the drug is influenced by pH.

- For example, acidic drugs such as aspirin are absorbed better and faster in an acidic environment. Thus, it is suitable for oral use to be absorbed in the stomach.  On the other hand, basic drugs such as codeine will be absorbed better in the small intestines.
However, a pharmacist should also assess the changes of pH value at the area of absorption. For instance, food can change the pH of gastric environment and thus affects the absorption of acidic drugs.

(4) Route of administration
- For intravenous injection, there's no absorption in the intestine (by pass first pass metabolism). Meanwhile, for oral drugs such as tablets will undergo dissolution and disintegration to increase its surface area for absorption.

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Group members from the left:
Ho Hui Ting, Noorliza Bt Mohd Khairi Kumaraguru, Christina Hoon Siew Keung, Benice Goh Sin Yee, Deepi Nair, Vanmathi

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Pharmacokinetic
Absorption-Related to body
1. Gastric motility
The stomach is an organ located between the esophagus and small intestine. It's responsible for grinding food down and mixing it with stomach acids so that nutrients from food can be absorbed in the small intestine. Under normal conditions, the stomach empties its contents at a controlled rate.
- The rate of gastric emptying may alter the rate of absorption of most if not all orally administered drugs.
- Food, hormones, posture, peritoneal irritation, severe pain, gastric ulcer, diabetes and other metabolic diseases, as well as drugs such as alcohol, anticholinergics, narcotic analgesics, ganglion blocking drugs, antacids and metoclopramide all influence the rate of gastric emptying and they will, in turn, change the rate of absorption of another drug.
- In most instances, increasing the rate of gastric emptying and gastro-intestinal motility increases the rate of absorption of a drug but, for digoxin and riboflavin, increased gastrointestinal motility is associated with a decrease in the rate of absorption.
-Delayed drug absorption due to altered gastric emptying usually results in therapeutic failure, especially if the drug has a short biological half-life

2. Drug- food interaction
A drug-food interaction occurs when the food and medicine interfere with one another, causing undesirable effect to the treatment plan.Drug-Food interaction
i.Grapefruit juice
Interact with Calcium channel blocker (Felodipine, Diltiazem) used to treat hypertension.
Grapefruit will increase the effect of these medicine as it decrease the CYP3A4 in metabolism

ii. Grapefruit juice
Interact with statin medication (Lovastatin, Atorvastatin, Simvastatin) used to treat high blood cholesterol, reducing risk of coronary disease. It increase the effect of these drug, increasing risk of side effect

iii. Dairy product
Interact with antibiotic (Ciprofloxacin, Tetracycline) used to treat bacterial infection. Milk, yogurt and cheese can decrease or prevent absorption of antibiotic as the diary product bing to antibiotic to form insoluble compound

3. Age
Weakening of GI movement, slow gastric emptying rate and increase gastric pH in the elderly affect the absorption of the drugs into body

Example :Calcium carbonate requires acidic environment for better adsorption.Increase in gastric pH due to age decrease calcium absorption and increase the risk of constipation in the elderly.

4.Disease state
Disease state:
Pharmacist should take account of the disease state of patient because it may decrease contact time of drugs, leading to decrease in absorption of drugs.

Example
Malabsorption syndrome refers to a number of disorders in which the small intestine cannot absorb enough of certain nutrients and fluids. Small intestine often has trouble absorbing can be macronutrients (proteins, carbohydrates, and fats), micronutrients (vitamins and minerals), or both.

If the patient is having diarrhea, it will speed up the passage of substances through the digestive tract, reduce the time that the drug in contact with absorptive surface. Eventually. It may reduce drug absorption. At the end, the concentration drug in body fails to achieve the therapeutic level, leading to ineffectiveness of drug and failure of quality use of medicine.
For example, if the patient is having significant diarrhea and she takes the oral contraceptive pill (OCP) at the same time, she may fail to achieve the effective contraception due to the low absorption of OCP. Hence, we have to suggest the patient to continue to take the OCP on schedule and take a backup birth control methods until she starts the next period. The example of barrier method includes the use of condoms or diaphragm.

Group member
1. Cheang Yue Ying
2. Lu Lei Chee
3. Lok Xue Min
4.Lu Lei Chee
5.Ting Mei Deng
6.Woh Kah Lok

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Group name: Sassy Gurlz

1. Perfusion of organ :
-Organ ; kidney must be in good condition so that the drug can be excreted properly.

-Example : Metformin is contraindicated for renal failure patient because it can potentially cause an increase metformin concentration and lactic acidosis.

2. Protein Binding
-  Drug that are highly protein bound may differ from those that are minimally bound in terms of tissue penetration, half life and rate of elimination

- example: Digoxin is highly bound to protein in cardiac tissue. When hypoalbuminemia occur,  digoxin that are usually protein bound are free in the plasma,  this will lead to faster elimination.

3. Drug Metabolism
- removal of drug from body in the form of metabolite and unchanged drug through urine,  bile and faeces.

- if a drug is metabolized in liver and patient have liver problem,  so less drug will metabolized causing less elimination of drug
- example : warfarin,  the elimination is almost entirely in metabolized form which is hydroxywarfarin and small amount is excreted unchanged. 80% is excreted through urine while 20% through faeces.

Group Members:
1. Nor Nadia Abidin
2. Saidatul Umairah
3. Nureen Irdina Hasya
4. Alisya Syafiza
5. Nur Siratul Syafinaz

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Pharmacodynamic

Pharmacodynamic

1. Physiological condition

The drug administered can affect those with different physiological conditions such as pregnancy, diabetes and hypertension.

Example: Warfarin in pregnancy.

Warfarin cannot be administered to a pregnant mother as warfarin can passes through placental barrier and causes bleeding in fetus. Abortion, stillbirth and preterm birth may occur.

2. Age

Paediatrics and geriatrics have different needs with normal adults.

For elderly subjects, they are less sensitive to the effect of verapamil in cardiac contraction. Also, salbutamol and propranolol reported to reduce responses with age.

3. Drug interaction

Precautions should be taken if two or more drugs are taken by a patient as it can either causes toxicity or lower therapeutic effect.

Example: Warfarin + NSAIDS cause greater risk of serious GI bleeding. NSAIDS increase gastric irritation and erosion of the protective lining of stomach, assisting in GI bleeding. Additionally, NSAIDS decrease cohesive properties of platelets that are necessary in clot formation.

4. Disease state

Example: kidney disease has 4 stages.

For every stage, kidney function especially GFR decreases. Therefore, the drug that will be secreted through kidney must be avoided or reduce the dose. Example of drugs: some antibiotics, b- blocker

For stage 3, the kidney is getting worst and cannot do the regular function of a kidney. So, it depends on dialysis to remove toxic from body. Stage 4 the patient must undergo kidney transplant

1. Nurul Atiqah binti Ismail
2. Syafawati binti Ajarullah
3. Nurul Diyanah binti Zulazlan
4. Munira binti Mohd Zuki
5. Nur Syafiqah binti Abdul Salam
6. Nur Azmira Liza binti Noor Azhuan @ Atan

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Pharmacokinetic > distribution > related to body

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Pharmacokinetic > distribution > related to body

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Group : AMBOI AMBOI :)

1) VASCULARITY
Drug distribution equilibrium(entry & exit rates are same) between blood and tissue reached more rapidly in richly vascularized areas (highly profused organ). And later in lessly profused organ. This is common in lipid soluble drug

Example: Thiopentone sodium (general anasethetic) when given, will distributed to brain(highly profused organ) first then other part of body which is lessly profused organ

2)Physiological barrier
- drugs distribute by passive process and the driving force is the concentration gradient between blood and ECF until equilibrium achieve.
-it refers to simple capillary barrier, blood brain barrier, blood-placental barrier, blood-CSF barrier and blood-testis barrier
- drugs that can across BBB must be highly lipid soluble and partially ionized

Example: Levodopa is more preferrable to treat Parkinson due to its high lipophilicity and it can cross BBB rather than using Dopamine.

3) TRANSPORT MECHANISM
Transport mechanism is process which drug moves from site of administration to the bloodstream via different mechanism to show effect.Hyrdophobic low molecules drug may penetrate by simple diffusion however most of the drugs need transporter for trans-membrane transport. Presence of transporter at membrane facilitate the movement of drug into or out of cells so that ADME processes are more deterministically governed.

For ex: Metoclopramide is dopamine antagonist used to treat nausea & vomiting. It is administer through oral tablet,solution or sometimes iv. It is rapidly well absorbed from GI tract.Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain.Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.

4)DISEASE STATE
Different diseases affect different type of drugs. Renal diseases cause hypoalbuminemia due to less protein, so toxic levels of free drugs may present.

As an example, warfarin. it binds to protein albumin. For renal impairment patient, they have less protein albumin. therefore, the unbound free drugs would increase. Hence, toxicity increases

5)PLASMA PROTEIN
Drug undergo protein binding process. Blood components are mainly plasma protein and red blood cells. If drug highly bound to plasma protein, the lower amount of drug to be distributed. Protein binding can also increase the half life of drug as it is not filtrated by glomerular filtration and not metabolized.

Example: thyroxine(T4) is highly bound to protein than triiodothyronine(T3). Thus, half life of T4 is longer.

6) DRUG INTERACTION
if a number of drugs are simultaneously given, one drug can displace the other or it will interact with endogenous substance

for example, interaction of sulphonamide and bilirubin. When bilirubin is displaced, it may cause kernicterus in babies.

Group members:
NORADRIANA BINTI AZIZ
ANIS MAWARNI BINTI AMRAN
LINA FAQIHAH BINTI LOKMAN
NUR INTAN ATHIRAH BINTI ROSDI
SERI DHANIA BINTI MOHD ANUAR

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Absorption(Related to drug)

1) Physicochemical properties

The properties of the drug used affect the absorption such as the size of molecules and solubility of the drug.
E.g. Lipid soluble drug (Rifampicin) are more easily absorbed compared to water soluble drug (Penicillin) as it could pass the plasma membrane easier

2) Dosage form

The dosage form used to deliver the drug also affect the absorption of the drug.
E.g. A drug which is prepared in solution form (Paracetamol suspension) are more readily absorbed by the body compared to solid drug (Paracetamol tablet) as it first need to be disintegrated before being absorbed.

3) Area of use

The area where the drug is applied will affect how the drug being absorbed and exact its effect.

E.g. Topical lotion (Calamine lotion) exert its effect only at the site it being applied which is localised effect compared to normal oral drug which normally give systemic effect (Loratadine)

4) Route of Administration

The rate of absorption is also determined by its route of administration.

E.g. Paracetamol suppository which is administered trough rectum gives faster effect compared to normal paracetamol tablet which is taken orally.

Group name: Rise of Kingdom
(From left)
1. Ahmad Marwazi bin Mohd Suhaimi
2. Luqman bin Shir Mohd
3. Muhamad Shauqiemuez bin Ramli
4. Meor Muhammad Azim bin Meor Shaharuddin
5.  Muhamad Noor Alfisyamil bin Taha

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Pharmacokinetic > Absorption
Four factors affecting absorption process are:

1) Gastric motility
-Gastric emptying rate is one of the main determinants of oral drug bioavailability and gastrointestinal drug absorption.
-If the stomach does not empty, practically nothing is going to get absorbed. Even drugs which are undissociated in gastric acid and fully dissociated in the small bowel are still predominantly absorbed in the small bowel because of its comparatively massive surface area.

-Example: Metoclopramide. It works by increasing the movements or contractions of the stomach and intestines. Hence it helps to increase the drug absorption.

2) Drug-food interaction
-A drug-food interaction occurs when your food and medicine interfere with one another.
-Drug-food interaction can delay, decrease, or enhance absorption of a drug.

-For example, you should not combine dairy and antibiotics because taking a medicine at the same time you eat can cause your body not to absorb the medicine

3) Age
-Absorption of drug can be affected due to ages.
-In young children, most organs are not completely matured especially in neonates and infants. While in elderly, decrease in small-bowel surface area, slowed gastric emptying, and an increase in gastric pH, changes in drug absorption tend to decrease absorption of drug.

-Example of drug is warfarin. It can increases bleeding risk after age 80, although the risk of thrombosis on the drug rises sharply after that age.

4) Disease State
-Absorption of drug in disease state
-Drug absorption can be effected by disease state.
Disease state can either limit the amount of drug that can be absorbed by the body or can cause other complications like toxicity due to the increase in concentration of the drugs in GI.

-For example, Graft-Versus-Hos-Disease (GVHD) involving the GI tract may reduce the absorption of cyclosporin, paracetamol and penicillamine.

1. Nurul Aina Aqilah bt Abdul Rahim
2. Wan Hanin Izzati bt Wan Ibrahim
3. Normiza Husna bt Ramlan
4. Nur Raihanah bt Radwan
5. Elis Hazerina Abd Rahman
6. Stefaney Kinjon
7. Syarah Munirah bt Shaharudin Amir

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Pharmacokinetic: Metabolism

1. Emily Tiong Sing Hui 136703
2. Nur Sakinah binti Mohd Siraj 136743
3. Khoo Yee Min 136710
4. Lee Wan Rong 136713
5. NG SHI TING 136732

1. Enzyme induction/ inhibition
Enzyme induction
-the phenomenon of increased drug metabolizing ability of the enzymes by several drugs and chemicals.
-occur by transcription of CYP450 mRNA which leads to overproduction of these enzymes in the liver and other extrahepatic tissues.
-exp: If taking Phenobarbitone together with warfarin, can cause therapeutic failures

Enzyme inhibition
-the phenomenon of decreased drug metabolizing ability of the enzymes by several drugs and chemicals.
-Exp: Aspirin inhibits the enzyme that catalyzes the 1st step in the synthesis of prostaglandins, which is responsible for the pains of athritis.

2. Genetic variation
- Warfarin is administered via a racemic mixture of the R- and S- stereoisomers. S-warfarin is 3-5 times more potent than R-warfarin and metabolized predominantly by CYP2C9. Patient with CYP2C9 gene polymorphisms may have impaired metabolism of S-warfarin, leading to decreased dose requirement, poor drug response thus, requiring more time to achieve a stable INR (international normalised ratio), and increased risk of bleeding.
- The blood test used to measure the time it takes for blood to clot is referred to as a prothrombin time test, or protime (PT). The PT is reported as the International Normalized Ratio (INR).It is important to monitor the INR (at least once a month and sometimes as often as twice weekly) to make sure that the level of warfarin remains in the effective range. If the INR is too low, blood clots will not be prevented, but if the INR is too high, there is an increased risk of bleeding.

3. Age
- Digoxin is used to treat heart failure and irregular heartbeats. It is metabolized in liver. Avoid doses higher than 0.125 mg per day as higher doses increase toxicity and provide little additional benefit in elderly. Therefore, dosage reductions may be needed.

4. Disease State
- Most dugs are metabolised by liver
- Depends on histological changes in the liver (acute or chronic hepatitis, cirrhosis) but may also depend on their origin (viral, toxic or immunological).
- Probe-based assays must be validated during disease, since the pharmacokinetics of the parent drug and/or of its metabolites may be altered.
- For example, in patients with compensated liver disease, drugs metabolized primarily by CYP2C19 (citalopram, diazepam, and methadone, among others) are metabolized slowly

5. Drug interaction (Ibuprofen)
- If patients are prescribed with Ibuprofen, they need to space out time between Ibuprofen and these drugs listed below because it may:
- Increased risk of gastrointestinal ulceration, perforation or haemorrhage with other NSAIDs (e.g. aspirin), antiplatelets, anticoagulants (e.g. warfarin), corticosteroids, selective serotonin reuptake inhibitors.
- Increased risk of hyperkalaemia and renal toxicity with ciclosporin, tacrolimus.
- Increased levels and risk of toxicity with lithium, methotrexate.
- Decrease antihypertensive effect of ACE inhibitors, angiotensin II receptor antagonist; natriuretic effect of diuretics.

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1.Perfusion of organ

-Perfusion of organ is defined as passage of fluid through circulatory system or lymphatic system to an organ or tissue, usually referring to delivery of blood to an area.
-Factor that affecting perfusion of organ: The rate of elimination increases as the blood flow to the kidney increases.
-Example: Angiotensin-converting enzyme  inhibitor such as Captopril will increase renal blood flow. Thus, it will increase the rate of elimination.

2.Protein binding

- The binding of drug to the plasma protein which affect drug elimination.

- Decrease in plasma protein binding leads to increase in free plasma fraction. This causes the increase in volume of distribution, decreases in elimination half life and decreases in total plasma concentration

-For example , carbamezepine is highly protein bounded (bind to serum albumin). The free drug concentration should be monitored to ensure no toxicity occurs. These drugs have high elimination half life up to 36 hours for a single dose and 16-24 hours for repeated doses

3.Drug metabolism

Drug metabolism involves a range of enzyme-mediated reaction in the liver which consists of Phase I and Phase II. Metabolites formed from phase II are more polar than that of Phase I.
Polar metabolites will be excreted more readily via kidney in urine and liver in bile.

Example: Phenytoin metabolizes in liver forming inactive metabolites. This inactive metabolites further undergoes glucoronidation and then excreted in urine.

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Pharmacokinetic - distribution related to body

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Pharmacokinetic - distribution related to body

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Group name: GAGAK
•Vascularity

- The distribution of a drug between tissues is dependent on vascular permeability, regional blood flow, cardiac output and perfusion rate of the tissue and the ability of the drug to bind tissue and plasma proteins and its lipid solubility.

- drugs distribute more to tissue with high blood flow

- The drug is easily distributed in highly perfused organs such as the liver, heart and kidney.

- It is distributed in small quantities through less perfused tissues like muscle, fat and peripheral organs.

- The drug can be moved from the plasma to the tissue until the equilibrium is established (for unbound drug present in plasma).

- heart/lungs/brain > muscle > cartilage/fat/tendons

•Physiological barriers: barriers in human body to protect against foreign materials that can affect normal body function.

Example: blood-brain barrier, a highly selective semipermeable border separating circulating blood from brain and ECF in CNS.

For a drug to be able to penetrate BBB, the drug must be lipid soluble.

Example of drug: cefotaxime in treating meningitis

•The transport mechanism of drugs depends on the solubility of the drugs itself. The water soluble drug will stay within the blood and interstitial space.

the fat soluble drugs distribute and rapidly enters and pass through membrane and concentrate in fatty tissues.

- There are bound drug and unbound drug. Bound drug will be distributed throughout body by plasma protein while the unbound drug will exhibit pharmacological effect.

- example : 97% of warfarin will bounded to plasma protein while 3% is free drug which the active one.

•Concurrent diseases affecting the patient, including the one for which the drug is used, can modify drug response. Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow.

The distribution can also be influenced by circulatory disorders modifying local blood flows and thus impeding drug entry into the tissues. Many diseases can alter hepatic and/or renal clearance.

Example

Drugs that are largely metabolized in the liver are affected by liver diseases such as cirrhosis.

This affect not only the metabolism and excretion of drugs but also their absorption (through first-pass effect).

ie :- Macrolide antibiotics like erythromycin, azithromycin, chloramphenicol, lincomycine, and clindamycin which are excreted and detoxified by liver should be used with cautions in these patients.

In patients with a compromised renal function, urinary excretion of drugs is diminished and affect the pharmacokinetics of drugs eliminated through metabolism which can induce toxicity.

ie :- The opioid drug pethidine should not be given to patients with renal insufficiency.

•Plasma protein.

-drug in blood exists in two forms ; unbound and bound.

-the plasma protein binding depends on the drug affinity to the protein.

-Protein binding can influence the drug's biological half-life.

-The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.

-  The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form

Example of drug that is highly bound to protein : Amiodarone Hydrocholride tablet(T1/2 : 58 days)

•Between diazepam and phenytoin

-diazepam displaces phenytoin from plasma proteins, resulting in an increased plasma concentration of free phenytoin and increased risk of toxicity.

Group members:
Puteri Nur Liyana
Nur Izatie Nabila
Nurhidayati
Nurul A'in
Nuralyssa
Nur Aida Fatini

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Group Joker
1. Jimmy Lau Lee Yan
2. Warren Goh Qiao En
3. Lai Jun Hua
4. Ooi Yen Hoe
5. Tan Jian Pin
6. Tan Min Yi

Pharmacodynamic:

1. Physiological condition
A condition where the physiological state of an organ is modified or impared. This causes inability of the impaired organ to operate normally and affects the ADME of certain drugs.
Example: Carbimazole should not be given in pregnant woman as it can cross the placental barrier.

2. Drug interaction
The effects of one drug is potentiated or decreased by another drug when given concomitantly.
Example: Diclofenac decreases efficacy of perindopril.

3. Age
Different age may have different levels of metabolic functions.
Example: Chlorpropamide glyburide should be avoided in elderly.

4. Disease state
Progression of disease in a patient.
Example: Patient with renal impairment needs dose adjustment for Metformin.

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Pharmacokinetic > Metabolism (related to the body)
 Pharmacokinetic > Metabolism (related to the body)
 Pharmacokinetic > Metabolism (related to the body)

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Pharmacokinetic > Metabolism (related to the body)
 Pharmacokinetic > Metabolism (related to the body)
 Pharmacokinetic > Metabolism (related to the body)

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Enzyme induction/inhibition

Once ingested, drug will be metabolized with the aid of enzymes present in our body. At the same time, the enzymes in our body might also interact with the drugs as such that it can either further potentiates or inhibits the drug activity. One of the most common and important enzyme group involved in the metabolism of drugs is the cytochrome p450 superfamily.

For example, grapefruit juice can inhibit cyp3a4 enzyme. So, patients taking drugs metabolized mainly by this enzyme, such as atorvastatin(cholesterol-lowering drug), are advised not to drink grapefruit juice as this can interfere with the metabolism of statin drugs. Ingestion of both substances will results in an an increased level of drug in the blood, leading to toxicity.

Genetic variation

Patient response to drugs varies widely because of genetic variation. This is because genetic influences on drugs metabolism may interect with the intrinsic (physiologic) and extrinsic (cultural, behavioral and environmental) characteristics of a person.

For example, differences in genetic coding between white and black people may explain the pathophysiology different of hypertension between these two races. Typically, black people patients require a high dosage of angiotensin-converting enzyme (ACE) inhibitors or combined therapy with low-dose diuretics to reduce blood pressure effectively. Although the risk of ACE-related angioedema is generally low, there is some evidence that it is more common in blacks.

Age

Metaprolol is medication with high hepatic clearance have been shown to have a lower hepatic clearance in older people when compare with younger people.

Disease state

Acetaminophen altered metabolism and depleted glutathione stores would expected to increase accumulation of hepatotoxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI) in liver disease patient.

Drug interaction

Drug interaction can be defined as an interaction between a drug and another substance either way other drugs or with foods. This can prevent the drug from peforming as expected. The effect can be enhanced or reduced.

Example : drug-drug interaction between warfarin and aspirin. These drugs have opposing effects which would increase the risk of bleeding.

Group name : SAMOSA

From top left
1. Nur Ashiqin Binti Khairul Anuar
2. Nur Farihah Amni Binti Raziyun
3. Sarah Syahirah Binti Sabri
4. Nur Hidayah Binti Abdul Mutalib

From bottom left
5. Nur Amirah Binti Ahmad Sabri
6. Aimi Syahirah Binti Joni

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Definition:
-Drug distribution refers to the movement of a drug and from the blood and various tissue of the body (for example, fat, muscle, and brain tissue) and the relative proportion of drug in the tissue.

Physicochemical properties:
- molecular size: 420.43gram/mol
- Lipid solubility: insoluble in alcohol, ether. Distribute throughout body water, but distribute poorly in body fat.

Duration of action:
-Short acting theophylline last for 4 to 6 hours. Example is aminophylline. Long acting theophylline will last for 12 hours such as Theo-Dur. This medication works within 30 minutes.

Therapeutic effects:
- Theophylline competitively blocks phosphodiesterase which increases cyclic adenine monophosphate (cAMP) tissue concentrations causing bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion.

Toxic effects:
- you must monitor the serum theophylline level to avoid toxicity due to its narrow therapeutic range.
- The risk of severe toxicity increases with increasing serum level but older patients and patients who have acute ingestion complicating chronic use will have a much higher risk of toxicity for the same serum level.
- Behaviour: convulsions or effect on seizure threshold
- GI : hypermolitility, diarrhea
- Contraindicated with hepatic patients, therefore you should reduce the dose of theophylline
- Dont use with alloprinol because it will increase plasma concentration.
- Phenytoin and other antiepileptic decrease plasma concentration.
-Increase the risk of synergistic toxicity when given with halothane and ketamine.
- Antagonistic effect of adenosine and competitive neuromuscular blockers
increase bronchospasm with beta blockers.
- Toxicity is increased by erythromycin, cimetidine, and fluoroquinolones, such as ciprofloxacin. Some lipid-based formulations of theophylline can result in toxic theophylline levels when taken with fatty meals.

Group members (from left to right)
Khor Chai Yee
Lim Woan Yi
Cheah Susie
Leow Shin Shyan
Chai Juan Ying

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SFactor effecting drug elimination process:

1) Perfusion of Organ
-Refer to the passage of fluid through circulatory system or lymphatic system.
-By affecting the blood flow in circulatory system, we can control the rate of elimination of drug.
-If the drug cause the blood flow to increase then the rate of that drug elimination will also increase and vice versa.
-For example, Hydralazine, will dilate the blood vessel in the circulatory system to increase the rate of elimination of drug.

2) Protein Binding
-Refer to degree to which medication attach to protein within the blood.
-If the peecentage is higher so the rate of drug elimination decrease because the half life of the drug is higher.
-Example, warfarin will take longer time to be excreted because of its longer half-life as 99٪ of its will bind to plasma protein, which is albumin.

3) Drug Metabolism
-There are some drugs that can be elminated in both active and inactive form. Example, captopril. Captopril is metabolized in the liver but being excreted through the kidney in form of active and its metabolite. Thus, the elmination is increased compared to other drug. High tendency of hepatoxicity

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1. Physicochemical properties
- Physicochemical properties influence the way in which drug reaches the site of action from site of application. Hydrophobicity, lipid solubility, molecular size, degree of ionization at physiological pH can influence the drug distribution.
- For example, hydrophobic drug will bind more strongly to serum albumin than the hydrophilic one. Thus there is low fraction of free drug. The high protein bound drug is hard to diffuse and thus less extensively distributed to tissues. For example, warfarin is approximately 99% protein bound especially to albumin. As a result, it has a small volume of distribution.

2) Duration of action
- is the length of time a particular drug is effective.
- the longer the half-life, the longer the duration of action, the less frequent the drug need to be administered to patient.
- duration of action depends on several factors and one of it is half-life of drugs.
- for example, amiodarone is poorly bioavailable and undergoes extensive heterohepatic circulation, after discontinuing the drug therapy, the effect of amiodarone still continue for 2 weeks to months due to long half-life (half-life of amiodarone: 15-142 days).

3) Therapeutic Effect
Drugs have effect on the body. Our goal is to have the effect of drug to be therapeutic. A drug's theraoeutic effect is the desired effect for treating a disease.
Example: Perindopril
Perindopril is an ACE inhibitor. It works by relaxing the blood vessel and decreasing aldosterone, thus reducing sodium and water retention and lowering blood pressure. Perindopril is used to treat high blood pressure, prevent stroke, health attacks and kidney problem.

4) Toxic Effects
- occurs when too much of a drug in bloodstream which leads to adverse effects
- Primary action from overdose ( Coumadin & bleeding )
- Secondary action from effect of medication besides the desired effect ( antihistamine for allergies & drowsiness )
- Hypersensitivity ( excessive responsiveness to either primary or secondary action of drugs)
- other eg : DIGITALIS TOXICITY (nausea, vomiting, diarrhoea)
The patient may experienced palpitation of typical rhythm disturbance with the heart

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Ng Fung Yian
Chin Wei Theng
Sharlotte Goh
Tan Hui Qi
Nur Shafiqah Mohd Ridzuan
Khairun Nisa Rohaidzat

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1)Duration of action

Onset of action is the duration of time it takes for a drug's effects to come to prominence upon administration.
With oral administration, it typically ranges anywhere from 20 minutes to over an hour, depending on the drug in question.

For example
The time to peak plasma concentration of pracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.

2) Toxicity
The Toxicity of drug during distribution occur when the drug doesn't not distribute well in the body. This is due to overdose or there is interaction between drug and protein in body. The drug can't penetrate well in the specialize area.

For example
Doxycycline have high protein binding , so it tend to distribute for a long time in our body

3)Therapeutic effect refers to the response(s) after a treatment of any kind, the results of which are judged to be useful or favorable

Example:
Metformin

Therapeutical effect: Distributes and concentrates in liver, kidney and gastrointestinal tract; partitions into erythrocytes. Metformin is a biguanide antihyperglycaemic agent which improves glucose tolerance by lowering both basal and postprandial plasma glucose. It decreases hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, delays intestinal glucose absorption, and improves insulin sensitivity by enhancing peripheral glucose uptake and utilisation.

4) Physicochemical Properties
Physicochemical properties is the ability of a chemical compound to elicit pharmacological and therapeutic effect is related to the influence of various physical and chemical properties of the chemical substance on the bio molecule that it interact with.

Factors affecting physicochemical properties :

• Solubility
• Partition Coefficient
• Dissociation Constant
• Hydrogen Bonding
• Ionization of Drug
• Complexation
• Surface Activity
• Protein Binding
• Isoterism
• Lipophilicity

Explaination :
• Solubility - The use of cosolvent such as PEG can improve solubility.
• Partition Coefficient - Reduce in logP will increase the aqueos solubility.

Example :
• Solubility remains an important requirement for a CNS drug, Doxorubicin was tested to had high aqueous solubili

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2) MOHAMMD AMIRUL IKMAL BIN MOHAMMAD NOOR
3. AFIF FAHMIEY BIN RAZALI
4) JASON LIOW SU BEE
5)FAYMIE ROMEO
6)HO JIA HAO

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Pharmacokinetic > Elimination

Three factors affecting elimination process are:

1) Perfusion of organ
- Refers to passage of fluid through circulatory system to an organ usually refers to delivery of blood to capillary bed.
- By increasing blood flow to the kidney increased the rate of elimination.

- For example, dopamine causes vasodilatation of renal vessels will enhance elimination.

2) Protein binding
- A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can diffuse through membrane.
- Bounded drug will not be eliminated compare to drug in unbounded form.

- For example, changes in albumin level affects phenytoin elimination.

3) Drug metabolism
- Breakdown of drug by specialized enzymes.
- Increased metabolism cause a decreased in plasma half life which eventually will enhance elimination.

- For example, donepezil is hepatically metabolized and the predominant route for both parent drug and its metabolites is renal.

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