- 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

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. 

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