Quick Main Pathophys Revison

Receptor Antagonist

(Blocker)= a drug that binds to a receptor and blocks access of the endogenous molecule, thus ↓ the normal response (ie. they block the receptor).

Inflammation - Cellular Exudate

(Migration of WBC to the area of injury) Cells that travel out of capillaries are the neutrophils and macrophages Macrophages are heavy eaters compared to neutrophils (amount of bacteria they can ingest before turning toxic) ALSO mast cells which release chemicals Other less major cells - Eosinophils - Natural killer cells - Platelets

Classic symptoms and signs of inflammation

- Redness - Swelling - Heat - Pain - Loss of function

Inhalation Administration

1) Aerosol 2) Dry Powder 3) Nebulised solution ADVANTAGES - Rapid access to circulation (large surface area) - Direct access to target tissues - Solution of drugs can be atomised and the aerosol inhaled DISADVANTAGES - Difficult the regulate does accurately - Cumbersome methods of administration - Gases and volatile drugs may produce irritation of the mucosa (and pronounced coughing)

Cytochrome P450 Enzymes Can

1) Insert an oxygen into a C-H or N-H bond to give corresponding hydroxyl derivative 2) Catalyse the oxidation of alkene or aromatic II-bonds 3) Add an oxygen atom to the electron pair of a nitrogen or sulfur atom, resulting in the formation of an N-oxide or S-oxide They find unusual molecules and add oxygen atoms to them. In some cases, this has the effect of making the molecule more soluble in water, making it easier to flush out of the body. The added oxygen also provides a ready handle for other detoxifying enzymes to take hold and further modify, and destroy, these toxic molecules

Mechanisms that cause shock

1. Hypovolemic shock - decreased circulating volume 2. Cardiogenic Shock - decreased cardiac output 3. Distributive Shock - vasodilation 4. Septic Shock - frequently includes vasodilatation, and loss of intravascular volume due to 'leaky capillaries' 5. Toxic shock syndrome - caused by staphylococcal or streptococcal exotoxins

Stages of shock

1. Initial-onset of shock 2. Compensatory mechanisms in shock 3. Progressive (decompensated shock) 4. Refractory

Factors effecting absorption

1. Route of administration or formulation (SC vs inhalation) 2. Circulation/blood flow at absorption site (eg.IM vs SC - less blood vessels in fat) 3. Surface at absorption site (thickness & amount of surface area) 4. Concentration of administered drug 5. Lipid solubility (lipid nature of membranes \lipid soluble drugs have ↑ absorption) Based on Formulation Factors: 1.Disintegration time 2.Nature & type of dosage form 3.Pharmaceutical ingredients 4.Product age & storage conditions Based on patient: 1.Age and sex 2.Gastric emptying rate 3.pH of GIT 4.Surface area of GIT 5.Intestinal transit 6.Blood flow to GIT. Based on property of drug 1.Drug solubility & dissolution rate 2. Particles size & effective surface area 3. Polymorphism & amorphism

Effects of Oncogenes - Angiogenesis

1.Angiogenesis must occur in order for a tumour to enlarge 2.Primary tumours 3.Metastasis

Drug Action - Ion Channels

3 Channels. cell membranes are complex structures that regulate the flow of ions in and out of the cell thorugh ion channels. This maintains electrochemical gradient between the interior and exterior of the cell. Eg. calcium channel blockers

Oedema: Lymphatic channel obstruction Example

A condition of localised fluid retention caused by a compromised lymphatic system. Most frequently seen after lymph node dissection, surgery or/and radiation therapy. Common in breast cancer sufferers

thromboembolism

A dislodged blood clot (when a piece of the blood clot begins to circulate the body)

Adhesions

A fibrous band of scar tissue that binds together normally separate anatomical structures / the abnormal union of surfaces normally separate by the formation of new fibrous tissue resulting from an inflammatory process

Down Syndrome (Trisomy 21)

A genetic disorder caused by the presence of all or part of a third copy of chromosome 21.

Chemical Mediator of Inflammation - Kinins (Bradykinin ect.)

A plasma protein, kininogen, is split by the enzyme kallikrein found in plasma, urine, saliva, and in lysosomes of neutrophils and other types of cells. Splitting releases active kinin peptides. Same as for histamine. Also induce chemotaxis of leukocytes and prompt neutrophils to release lysosomal enzymes, thereby enhancing generation of more kinins. Induce pain.

Shock

A state of inadequate tissue perfusion 1. As perfusion decreases, O2 delivery to cells is decreased. 2. Aerobic metabolism of cells shift to anaerobic metabolism with increased production of CO2 and accumulation of lactic acid. 3. Cellular function decreases and inadequate. 4. If shock persists, irreversible cell damage and death can occur.

Hypertrophy

A type of adaptation where cell/tissue/organ increase in size. Causes can be physiologic (such as myometrium during pregnancy) or pathologic. Eg. Hypertension where the left ventricle of the heart pumps against higher pressure therefore cardiac muscle has to do more work which results in myocytes increase their syntheses of proteins and increase in size. = this can result in the patient developing left ventricular hypertrophy

Metaplasia

A type of adaptation where it is a replacement of a tissue/cell to another cell/tissue type (Changes Structure). Causes are due to the original cell/tissue not being strong enough to withstand the new environment so they change into another cell/tissue type which is more suitable to the new environment. It is an adaptation from one normal cell type to another normal cell type. Eg. GORD

Atrophy

A type of adaptation where the cell decreases in size. Causes include regular ageing and/or withdrawl of growth factors eg. Breast tissue after oestrogen levels decrease with menopause. Other causes of atrophy include ischaemia, nerve damage and disuse.

Hyperplasia

A type of adaptation where the number of cells in tissue/organ increase. Eg. 1. Hormonal hyperplasia - occurs when hormone responsive cells (breasts, prostate, uterus) undergo cell division when hormone stimulation increases (puberty) Pathologic hyperplasia - abnormal increase in cell division due to tissue injury or excessive hormonal stimulation. Can cause metaplasia, dysplasia, neoplasia eg. Enlarged prostate

Dysplasia

A type of adaptation where varied cell size, shape, organisation, appearance of abnormal cells within tissue. The most common site for this to occur is in the cervix when subject to chronic inflammation or HPV (detected in a papsmear)

Apoptosis

A type of cellular death that is known as 'cell suicide', essential to remove old or dying cells from the body. It is effective on only a single cell and is commonly known for its anti-cancer mechanism.

Necrosis

A type of cellular death which follows the process when the cell explodes and releases all its chemicals around it. It can be - 1. Coagulative- when proteins denature and break down and for coagulation (firm opaque state 2. Liquefactive- seen in soft tissue (brain) 3. Fat - takes place in fatty tissue, fat cells die Gangrenous - mixture of ll of the above ( going to turn black)

Pathophysiology

A type of study that changes to the body due to a disease or disorder.

drug transport systems

All the physiological processes mediating absorption, distribution, metabolism and excretion rely on 3 drug transport systems: 1) Membrane openings or pores 2) Passive transport 3) Active or carrier transport Drug molecules are transported from one body compartment to another by way of plasma For a drug to gain access to the interior of the cell of body compartment, it has to penetrate cell membranes

Pathophysiology of anaphylaxis - Effector phase

Allergen cross-links IgE on surface of mast cells Causes widespread degranulation and release of histamine which mediates inflammatory bronchospasm, vasodilatation, increased capillary permeability, and tissue oedema

oral administration

Also called enteral (Includes sublingual, buccal and rectal suppositories as well) ADVANTAGES - Safest, most convenient snd economical - Patient self-administration - Home administration -Unsupervised DISADVANTAGES - Must pass through intestinal wall and then portal circulation to the liver - Both are common sites of 1st pass metabolism - Low bioavailability is most common with this dosage forms of poorly water-soluble, slowly absorbed drugs

Kinin System

Also present in the blood Proteins called the kinin's The main kinin is bradykinin. It is a smooth muscle contractor and can generate pain. It also causes vasodilation to increase fluid to that area + Smooth muscle contraction (bronchoconstriction) + Pain

Oncogenes

An oncogene is a gene that when mutated or expressed at abnormally-high levels contributes to converting a normal cell into a cancer cell.

Gaba agonist

Barbiturates and Benzos, when binded to the gaba receptor could lead to an influx of chloride ions, when both the gaba and gaba agonist bind to receptors more chloride ions enter the post synaptic cell, increasing gabas effect

Drug Metabolism

Biotransformation The process of chemical modification of a drug and is carried out by enzymes ~70% of drugs undergo metabolism to some extent and in some cases the products of metabolism (metabolites) have less biological activity than the parent drug If a drug is taken into the GI tract, where is enters the hepatic circulation through the portal vein, it becomes well-metabolised and is said ti show the first-pass effect In general, metabolism results in the formation of a more water-soluble compound or metabolite, which can then be excreted Prodrugs are the exception

Effects of Oncogenes - Telomeres and immortality

Body cells are not immortal and can only divide a limited number of times Telomeres are protective caps on each chromosome and are held in place by telomerase Telomeres become smaller and smaller with each cell division Cancer cells become immortal by repairing telomeres

Tissue binding

Bone- Some drugs have an unusual affinity for bone as it can become a storage site for tetracycline. This can prove to be a serious problem in pregnancy. Body Fat- Lipid soluble drugs have a high affinity for fat tissue as they are capable of storing and have low blood flow in fat tissue Blood Brain Barrier- Brain capillaries are less permeable than other body capillaries as they are lined by astrocytes. Drugs that cross the blood brain barrier are only soluble in lipids. Substances that easily cross the blood most anaesthetics and barbiturates. Placental Barrier - the membrane layers that separate the blood vessels of the mother and the foetus. However, this barrier does not afford complete protection to the foetus.

Genetic basis of cancer

Cancer arise through genetic mutations to: 1.allow proliferation (autocrine stimulation or increased in numbers of growth factor receptors) 2.disable apoptosis 3.damage tumour-suppressor genes To develop into a clinically significant tumour, cancer cells must not only have the ability for increased cell division but also must be able to invade surrounding tissues and provide for their own increased growth rate (e.g, grow their own blood supply [angiogenesis].

Drug Actions - Carriers

Carriers are proteins that facilitate the transport of ions and small molecules that lack lipid solubility (therefore cannot diffuse across biological membranes). Eg. SSRI

Chemical Mediator of Inflammation - Histamine as a Vasoactive Cytokine

Causes brief vasoconstriction followed by vasodilation Also causes an increase in capillary permeability by stimulating endothelial cells to react, opening the spaces between cells, which allows cells and proteins to move out of the vessel and into the tissues (oedema) Histamine receptors located on white blood cells help activate neutrophils and macrophages that provide the cellular inflammatory response Promotes vasodilation of local arterioles, increasing blood flow to injured area. Increases permeability of local capillaries, promoting formation of exudate. It can also serve as a chemotactic factor that calls eosinophils to the tissues

Chemical Mediator of Inflammation - complement proteins

Complement proteins are proteins that lyse the cell wall of an antigen. They are part of the nonspecific defense mechanisms of the immune system.

Ca channel blockers

Dilate the arteries and reduce the force of the heart's contractions by preventing calcium from entering the cells of the heart and arteries therefore lowering Bp. Also called calcium antagonists

Parenteral - Intramuscular

Direct injection into the Deltoid or Gluteus maximus muscles ADVANTAGES - Good administration of slow release/oily drug preparation; can be useful for non-complaint patients - More accurate dosing compared to subcutaneous but less accurate than IV- Simple and accessible DISADVANTAGES - Slower absorption than intravenous - Painful - Limited volume - Nerve damage, if done incorrectly - Potential for subcutaneous injection - Sterile or infected abscesses, chance of sepsis - Irritation or local allergic reactions - Absorption dependent on blood flow. May be danger of sudden absorption drugs (E.g. sudden overdose may result when perfusion to muscle improves)

Chemical Mediator of Inflammation - Prostaglandins

Fatty acid molecules produced from arachidonic acid found in all cell membranes; generated by enzymes of neutrophils, basophils, mast cells, and others Same as for histamine. Also induce neutrophil chemotaxis. Induce pain. (Some prostaglandins are anti-inflammatory.) Intensify histamine and kinin effect

Mutation

Faulty replication of a gene. A change in DNA template that can result in abnormal DNA, RNA and protein synthesis. Some occur by chance (spontaneous mutation).

Causes of anaphylaxis

Foods (peanuts, shellfish, berries), Venom (bees, Wasps) Medications(Penicillin/Antibiotics)Plants (Burning poison oak).

Macrophages

Found within the lymph nodes, they are phagocytes that destroy bacteria, cancer cells, and other foreign matter in the lymphatic stream. They move more slowly toward the area of inflammation (2-7 days) but once they arrive, they can survive longer than neutrophils, they provide a prolonged inflammatory response

Inflammation - Vascular permeability

Generating fluid exudate Mostly plasma coming out of the capillaries, it dilutes the toxins released by the tissue being damaged or released by the bacteria present. This also allows antibodies to travel to the area quickly Three plasma protein systems are activated - Complement system - Clotting system - Kinin system

Concentration gradient of drugs

IV fastest absorbed followed by IM and then oral Half-life- The time taken for the blood or plasma concentration of a drug to fall by one half Steady State - When the rate of drug administration equals the rate of drug elimination Loading Dose - 1 or a series of doses that may be given at onset of therapy with the aim of achieving Target plasma [drug] rapidly

Pathophysiology of anaphylaxis - sensitisation phase

Immune system encounters allergen and makes immunoglobulin E (IgE) against it No clinical features occur

Drug Actions

In general drugs act at 4 main types of regulatory proteins 1. Carriers 2. Enzymes 3. Ion Channels 4. Receptors 5. HAART antiretroviral

Fibrosis

In most tissues, healing occurs with at least some element of collagen deposition with fibrosis and scarring.

Concurrent Components of the Inflammatory Process

In place of inflammation only and responsible for the cardinal signs and symptoms of inflammation: 1) Increased blood flow (hyperaemia) - vasodilation 2) Increased vascular permeability (fluid exudate): exudation of fluids containing proteins like antibodies 3) Invasion by several different types of neutrophils and macrophages + At the site of injury, cells release molecular signals that cause a number of changes in the affected area:Vasodilation, increased blood flow, increased vascular permeability, and invasion by neutrophils and macrophages

Parenteral - Intravenous

Injected directly into blood stream via vein ADVANTAGES - Availability and effects are more rapid and predictable - Effective dosage can be more accurate (titrated) - No absorption problems - Easier for continuous infusions of drugs- Administration of large volumes of a drug- Irritating solutions can be used DISADVANTAGES - Complete sterility is essential - Pain and possible accidental intramuscular injection - Need someone trained to administer - Increased risk of immediate adverse effects - Not suitable fro oily or insoluble preparations

Parenteral Administration

Injection (Subcutaneous, intramuscular, intravenous, intrathecal or epidermal)

Parenteral: Subcutaneous

Injection beneath the skin into connective tissue or fat ADVANTAGES - Can be self administered - Good for some drugs requiring slow release into bloodstream DISADVANTAGES - Only suitable for a few drugs- Only small volumes usually administerable - Painful, bruising, skin reactions, necrosis, etc - Possibility of intravascular injecting accidentally - Variable distribution in different individuals (not very accurate method of dosing)

Fluid Compartments

Intracellular fluid (ICF) Extracellular fluid (ECF)

Functionalisation (Phase I) Reactions

Involves the introduction of a polar functional group into the molecule by oxidisation, hydrolysis, or reduction reactions These chemical reactions produce more water-soluble metabolites that may be more pharmacologically active than the parent compound or more uncommonly, toxic The Cytochrome P450 enzyme family are particularly abundant in liver cells. They are not only involved in drug metabolism but also in the metabolism of environmental pollutants, dietary chemicals and in the synthesis and metabolism of steroids, hormones, and fatty acids OIL RIG - oxidation is loss reduction is gain

Conjunction (Phase 2) Reactions

Involves the union of a suitable functional group present in the drug molecule with the polar group of an endogenous substance in the body The 4 substances involves in conjunction reactions are glucuronic acid, sulphate, acetyl-coenzyme A or glutathione The resultant molecule is more polar and therefore more water-soluble, enhancing urinary excretion Conjunction reactions are catalysed by a variety of different transferase enzymes

radiation therapy

Ionising radiation to a tumour results in damage to and death of the DNA of the cancer cells. Although the beam of radiation can be focused on the tumour by using sophisticated imaging techniques, there is almost always some collateral damage to surrounding healthy tissues.

Absorption from administration sites

It can affect both the rate at which onset of action occurs and the magnitude of the resulting therapeutic response 1) Oral 2) Parenteral 3) Inhalation 4) Topical

Complement System

Made up of 9 proteins circulating the plasma They are inactive by themselves but when they come across tissue damage, all those chemicals (cytokines) activate the complement system. They are capable of killing bacteria, making smooth bacteria rough, hence making it easier to phagocytose them The complement system can enhance inflammation + They opsonise encapsulated bacteria, making them easier to phagocytose + They include mast degranulation (anaphylatoxins) + They induce cell lysis and death

vasoactive cytokines

Mast cell activation may also be followed by the synthesis and release of lymphokines and cytokines Histamine and Serotonin The vasoactive effects of histamine and serotonin result in hyperaemia and the movement of fluid, cells, and proteins out of vessels and into the injured tissues

chemotherapy

Most chemotherapeutic agents target all rapidly dividing cells and therefore have significant toxicity to all tissues, especially healthy tissues that also have high replication rates, such as the gastrointestinal tract, bone marrow, hair, skin, and reproductive tract.

Necrosis vs. Apoptosis

Necrosis: bad, damage to nearby cells caused by lysis Apoptosis: good; for normal functioning of cell. Cell shrinkage, caspase activation,

Oedema

Occurs due to a decrease in oncotic pressure. It is an accumulation of fluid within interstitial spaces which results from fluid movement from capillaries or lymphatic channels into the tissue as a result of: 1. Increased capillary hydrostatic pressure 2. Decreased plasma oncotic pressure 3. Lymphatic channel obstruction 4. Increased capillary membrane permeability

Inflammation - Pain

Pain also results from the release of bacterial toxins, and the sen- sitizing effects of released prostaglandins and kinins. (Aspirin and some other anti- inflammatory drugs reduce pain by inhibit- ing prostaglandin synthesis.)

Oedema: Increased capillary hydrostatic pressure Example

Peripheral vascular disease: When pressure increases in legs as a result of PVD, leading to oedema and swelling in legs

Oedema: Decreased plasma oncotic pressure COP Example

Plasma proteins are reduced thus results in oedema 1. Loss in the urine as in nephrotic syndrome or eclampsia 2. Malnutrition syndrome as in Kwashiorkor Decreased production as in liver failure / Cirrhosis

Chemical Mediators of inflammation

Produced by mast cell + Histamine + Complement + Kinins + Prostaglandins + Interleukins Not produced by mast Cell + Serotonin + Bradykinin

Chemical Mediator of Inflammation - Interleukins

Produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation •Examples •IL-1 is a proinflammatory cytokine •IL-10 is an anti-inflammatory cytokine

Signs and symptoms of anaphylactic shock

Respiratory: dyspnea, wheezing, swelling upper airways, cant speak, watery eyes, coughing, stuffy nose Cardiac: Hypotension, increase heart rate GI: vommiting, nausea, diarrhoea, pain Skin: itchy, red, swollen

Phase 1 Metabolism

Results in small chemical changes that make a compound more hydrophilic, so it can me effectively eliminated by the kidney's These reactions usually involve either adding or unmasking a hydroxyl group and usually involve hydrolysis, oxidation or reduction mechanisms Cytochrome P450 enzymes are responsible for most of this phases reactions

6 rights of medication administration

Right patient, right drug, right dose, right time, right route, right documentation

Mechanism of an acute allergic (immediate hypersensitivity) response.

Sensitization stage: 1. Antigen invades body 2.Plasma cells produce large amounts of class IgE antibodies against allergen 3. IgE antibodies attach to mast cells in body tissues Subsequent (secondary) responses 4. more of the same antigen invades body 5. Antigen combines with IgE attached to mast cells, which triggers degranulation and release of histamine (and other chemicals). 6. Histamine causes blood vessels to dilate and become leaky, which promotes edema; stimulates secretion of large amounts of mucus; and causes smooth muscles to contract. (If respiratory system is site of antigen entry, asthma may ensue.)

SSRI

Serotonin is a neurotransmitter which influences mood, emotion and sleep. SSRI works by blocking the re-uptake of serotonin which means more is available in the synapse to bind to more receptors on post synaptic nerve

Shock

Shock is a state of inadequate perfusion ( pO2), which does not sustain the physiologic needs of organ tissues particularly the brain.

Topical Administration

Skin, eyes, ears and nose(mucous membranes) ADVANTAGES - Local effects - Self administration - Can be rapid and relatively painless DISADVANTAGES - Sensitisation/allergies - Systemic toxicity - Very slow absorption - Most drugs have a high molecular weight and are poorly lipid soluble, so aren't absorbed via skin or mucous membranes

Clinical manifestations of cancer

Some types of cancer do not cause any symptoms until the disease is very advanced. When symptoms do occur, they can be the result of the growth and invasion of the primary tumour, the presence of metastases, or both. Additional manifestations of some cancers, called paraneoplastic syndromes, result from the release of hormones from the tumour Clinical manifestations of cancer: Pain, Fatigue, Cachexia (muscle loss), Anaemia, Infection, swollen lymph nodes

Pharmacology

Study of substances that interact with living systems, particularly their action and effects in living systems

symptoms of anaphylactic shock

The bronchioles constrict (and the tongue may swell), making it difficult to breathe, and the sudden vasodilation and fluid loss from the bloodstream may cause circulatory collapse (hypoten- sive shock) and death within minutes. Epinephrine is the drug of choice to reverse these histamine-mediated effects.

Clotting system

The clotting factors go out and they are required to seal off the bleeding if there is any + Stops bleeding + Prevent the spread of infection + Provides a framework for repair and healing

Neutrophils

The first phagocytes to arrive at the inflamed site. They ingest bacteria and debris A type of white blood cell that engulfs invading microbes and contributes to the nonspecific defenses of the body against disease.

inflammation

The immune response of body tissues to injury or infection, is an important component of innate immunity. Involves a complex biological cascade of molecular and cellular signals that alter physiological responses, ultimately resulting in the familiar clinical symptoms of pain, swelling, heat, loss of function and redness. + It is a vascular, cellular and chemical process

Oedema: Increased capillary membrane permeability Example

The inflammatory process alters capillary permeability therefore increased the movement of plasma into ECF

Elimination and elimination of a drug

The irreversible loss of drug from the body by the process of metabolism and excretion Excretion - only applies to the irreversible loss of chemically unchanged drug from the body in urine, bile, expired air or faeces. Kidneys are the main organs of excretion. more include Biliary excretionExpired air Sweat and salivaBreast milk Elimination - main organ is liver

distribution of a drug

The process of reversible transfer of a drug between one location and another (usually one is the blood) in the bodyAfter a drug enters the systemic circulation, it's distributes to the body's tissuesIt is generally uneven because of differences in blood perfusion, tissue binding, regional pH, and permeability of cell membranes

metastasis

The spread of cancer cells beyond their original site Cancer cell metastasis usually involves the following steps: 1.Local invasion: Cancer cells invade nearby normal tissue. 2.Intravasation: Cancer cells invade and move through the walls of nearby lymph vessels or blood vessels. 3.Circulation: Cancer cells move through the lymphatic system and the bloodstream to other parts of the body. 4.Arrest and extravasation: Cancer cells arrest, or stop moving, in capillaries at a distant location. They then invade the walls of the capillaries and migrate into the surrounding tissue (extravasation). 5.Proliferation: Cancer cells multiply at the distant location to form small tumors known as micrometastases.

Phase 2 Metabolism

These reactions usually involve adding a large polar group (conjunction reaction), such as glucuronide, to further increase the compound's solubility Transferase enzymes are responsible for most of this phases reactions E.g. Glucuronosyl transferase (UGT), N-acetyl transferase (NAT), glutathione S-tranferase (GST), and sulphotransferase (ST)

Effects of Oncogenes - Lytic Enzymes

Tumours frequently secrete lytic enzymes such as proteases, collagenases, plasminogen activators, and lysosomal enzymes that attack surrounding tissues and provide room for the tumour to expand. effect of these enzymes is to: 1.Break down the collagen structure of the tissues surrounding the tumour 2.Help the tumour cells access blood vessels to improve nutrient delivery 3.Enhance migration of tumour cells

4 major mechanism of hypersensitivity

Type I - is mediated by IgE and is known as allergy. Type II - includes tissue-specific reactions. Type III - is mediated by immune complex deposition. Type IV - consists of cell-mediated reactions (delayed hypersensitivity).

Pharmacokinetics

What the body does to the drug - 1. absorption of a drug 2. distribution of a drug 3. metabolism of a drug 4. excretion of a drug

Metabolism of Foreign Compounds

Xenobiotics such as drugs and toxins from the body An essential process designed to protect potential toxicity from whatever we eat The liver detoxifies compounds before they are distributed through the circulatory systemIn the liver, there are two main types of metabolism that deal with xenobiotics

Mast Cell

a cell filled with basophil granules filled with vasoactive and chemotactic cytokines, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions.

Receptor Agonist

a drug that binds to and activates a receptor and produces the same response as the endogenous stimulant.

Anaphylaxis

a loss of vasomotor tone due to ana- phylaxis, a systemic allergic reaction in which the massive release of the chemical messenger histamine triggers body- wide vasodilation. 1.Release of large amounts of chemical mediators into circulation from mast cells all over the body 2.Sudden severe decrease in blood volume (fluid moves to tissue) 3.General/systemic vasodilation 4.Oedema at the alveoli - Hypoxemia + Hypercapnia 5.Laryngeal oedema 6.Respiratory and circulatory impairment 7.Loss of consciousness 8.May be fatal if untreated Treatment with adrenaline (EpiPen)

Tumours

abnormal proliferation of cells, either benign or malignant.

Type I hypersensitivity

also called Immediate hypersensitivities or acute sensitivities IgE mediated (Allergy) Antigen binds to IgE that is bound to tissue mast cells and blood basophils, triggering release of preformed mediators (eg, histamine, chemotactic factors) and synthesis of other mediators (eg, prostaglandins, leukotrienes, platelet-activating factor, cytokines). These mediators cause vasodilation, increased capillary permeability, mucus hypersecretion, smooth muscle spasm, and tissue infiltration with eosinophils, type 2 helper T (TH2) cells, and other inflammatory cells.

p53 gene

also known as protein 53 (TP53), a tumour-suppressor gene that codes for a specific transcription factor that promotes the synthesis of proteins that inhibit the cell cycle It is important in multicellular organisms as it helps to suppress cancer "the guardian of the genome," "the guardian angel gene," or the "master watchman," 1.It can activate DNA repair proteins when DNA has sustained damage. 2.It can also hold the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle.) 3.It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable.

stricture/stenosis

an abnormal narrowing/ constriction of a bodily passage/ tubular organ, structure, or part (as from inflammation, cancer, or the formation of scar tissue)

Hypersensitivity

an exaggerated response by the immune system to a particular substance

Drug Action - HAART

antiretroviral Highly active antiretroviral therapy used to treat HIV-1 •Reverse transcriptase inhibitors •Protease inhibitors •Entrance (fusion) inhibitors •Integrase inhibitors

Cancer

any malignant growth or tumor caused by abnormal and uncontrolled cell division of eukaryotic cells.

Drug Action - Receptors

are cellular macro molecules concerned directly and specifically in chemical signalling between and within cells The combination of a hormone, neurotransmitter, drug or intracellular messenger with its receptor, initiates a change in cell function The receptor theory of drug action relies on the premise of structural specificity This means that a certain portion of the drug molecule selectively combines or interacts with the receptor to produce the pharmacological effect(Lock + Key - Drug + Receptor) Eg. Gaba agonist

malignant

cancerous 1.They exhibit rapid growth. 2.They lack a capsule/defined boundary and have a tendency to invade surrounding tissues. 3.They are composed of undifferentiated cells that exhibit large nuclei, frequent mitotic figures (actively dividing cells), and little to no tissue organisation (anaplastic). 4.They tend to metastasise to distant tissues and to lymph nodes. In short: Grow rapidly, not encapsulated, invasive, poorly differentiated, high mitotic index, metastasis (spread distantly)

Role of Histamine in anaphylactic shock

causes the following: + vasodilation which widens vessels which decrease Bp + Increase capillary permeability "Leaky" which decrease Bp, deplete intravascular space and swelling and decrease Cardiac output + Itching +bronchoconstriction - narrowing of airways causing resp. failure + Increase gastric Secretions +Contract smooth muscle in GI system WHICH ALL LEAD TO DECREASED TISSUE PERFUSION = SHOCK

Another name for oncotic pressure

colloid osmotic pressure (COP)

Inflammation - increased blood flow

hyperaemia The first cell to react to tissue injury is the mast cell Within seconds of cellular injury from any cause, the mast cell releases chemicals that initiate a vascular response This response consists of: 1) A brief vasoconstriction, followed by vasodilation 2) Increased vascular permeability in the area if injury These vascular changes allow cells and proteins to move out of the blood vessels and into injured tissuesFormation of an early transudate gives way to exudate into extracellular tissues

benign

mild, not cancerous 1.They are surrounded by a capsule that separates the tumour from the surrounding tissue. 2. The cells in the tumour are well differentiated, which means that the cells look relatively mature and much like the healthy cells from which the tumour first developed. 3. They do not invade surrounding tissues (although benign tumour growth may compress nearby healthy tissue). 4. They do not metastasise (spread) to lymph nodes or other tissues In short: Grow slowly, well defined capsule, non invasive, well-differentiated, low mitotic index, don't metastasis

Proto-oncogenes

normal gene that can become an oncogene in mammals due to mutations or increased expression.

Allergy

one of the most common forms of hypersensitivity found throughout the world. + range in severity from mild allergic rhinitis (hay fever) to rapidly fatal anaphylaxis. + Allergy is mediated by production of IgE antibody in response to exposure to specific exogenous antigens (called allergens).

Drug Actions - Enzyme

proteins that speed up chemical reactions. They convert a substrate (specific to enzymes -lock and key) into its metabolic products. Drugs can block enzymatic action or result in the production of other metabolites Eg. ACE# (angiotensin), transpeptidase#

fever

results from the effect of inflammatory cytokines TNF-alpha (Induces fever by acting as an endogenous pyrogen), IL-1, IL-6, and prostaglandins on the hypothalamus and vasomotor centre

Tumour markers

substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF or urine •Hormones •Enzymes •Genes Antigens used to: +screen and identify individuals at high risk for cancer +diagnose specific types of tumours +observe clinical course of cancer

cancer treatments

surgery, radiation, chemotherapy

Absorption of Drug

the process by which unchanged drug proceeds from the site of administration into the blood. Important for all routes of administration except intravenous administration. For absorption to occur, the drug has to cross a membrane (has a lipid bilayer) and into the blood vessels on the other side. Lipid soluble drugs can easily pass through the lipid membranes. Water soluble drugs have difficulty crossing cell membranes.

Difference between allergy and anaphylaxis

•Allergy is a local reaction •Anaphylaxis is systemic reaction -Occurs within minutes of re-exposure to antigen -Life threatening

Benefits of fever

•Suppresses microbial growth •Decreases minerals needed for bacterial replication •Facilitates immune response

Effects of Chemo

•fatigue (tiredness) •nausea, vomiting and loss of appetite •sores in the throat or mouth •changes to the skin, such as itching, redness, dryness and acne •diarrhoea or constipation (often due to the antinausea medication) •hair loss (some drugs cause hair to thin or fall out but many others don't cause any hair loss) •changes to your libido