Atopy or atopic syndrome is an allergic hypersensitivity affecting parts of the body not in direct contact with the allergen. It may involve eczema (atopic dermatitis), allergic conjunctivitis, allergic rhinitis and asthma. There appears to be a strong hereditary component.
The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli (see below). In response to exposure to these triggers, the bronchi (large airways) contract into spasm (an "asthma attack"). Inflammation soon follows, leading to a further narrowing of the airways and excessive mucus production, which leads to coughing and other breathing difficulties.
Mucus is a slippery secretion of the lining of various membranes in the body (mucous membranes). It is a viscous colloid containing antiseptic enzymes (such as lysozyme) and immunoglobulins. Mucus is produced by goblet cells in the mucous membranes that cover the surfaces of the membranes. It is made up of mucins and inorganic salts suspended in water. Phlegm is a type of mucus that is restricted to the respiratory tract, while the term mucus refers to secretions of the nasal passages as well.
It usually occurs after at least several minutes of vigorous, "aerobic" activity, which demands that normal nasal breathing be supplemented by mouth-breathing. The resultant inhalation of air that has not been warmed and humidified by the nasal passages seems to generate increased blood flow to the linings of the bronchial tree, resulting in edema. Constriction of these vessels then follows, worsening the degree of obstruction to airflow. This sequence generates symptoms similar to those seen in other forms of asthma, but occurs without the inflammatory changes that underlie them
Ipratropium is an anticholinergic drug (trade name: Atrovent) administered by inhalation for the treatment of obstructive lung diseases. It acts by blocking muscarinic receptors in the lung, inhibiting bronchoconstriction and mucus secretion. It is a non-selective muscarinic antagonist, and does not diffuse into the blood, which prevents systemic side effects.
Type 1 hypersensitivity is an allergic reaction provoked by reexposure to a specific type of antigen referred to as an allergen. Exposure may be by ingestion, inhalation, injection, or direct contact. The difference between a normal immune response and a type I hypersensitive response is that plasma cells secrete IgE. This class of antibodies binds to Fc receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE are "sensitized." Later exposure to the same allergen, cross-links the bound IgE on sensitized cells resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotriene, and prostaglandin that act on the surrounding tissues. The principle effects of these products are vasodilatation and smooth-muscle contraction.
In allergic reactions an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors.
In allergic reactions, mast cells remain inactive until an allergen binds to IgE already in association with the cell (see above). Allergens are generally proteins or polysaccharides. The allergen binds to the Fab part of the IgE molecules on the mast cell surface. It appears that binding of two or more IgE molecules (this is called crosslinking) is required to activate the mast cell; the steric changes lead to a slight disturbance to the cell membrane structure, causing a complex sequence of reactions inside the cell that lead to activation of the cell. Although this reaction is most well understood in terms of allergy, it appears to have evolved as a defense system against intestinal worm infestations (tapeworms, etc).
In allergic reactions, mast cells remain inactive until an allergen binds to IgE already in association with the cell (see above). Allergens are generally proteins or polysaccharides. The allergen binds to the Fab part of the IgE molecules on the mast cell surface. It appears that binding of two or more IgE molecules (this is called crosslinking) is required to activate the mast cell; the steric changes lead to a slight disturbance to the cell membrane structure, causing a complex sequence of reactions inside the cell that lead to activation of the cell.
They act on the β2-adrenergic receptor, thereby causing smooth muscle relaxation resulting in dilation of bronchial passages, vasodilatation in muscle and liver, relaxation of uterine muscle and release of insulin. Side effects such as insomnia, anxiety, and tremor occur in some patients.
The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines adrenaline and noradrenaline (also called epinephrine and norepinephrine in the
β receptors are linked to Gs proteins, which in turn are linked to adenylyl cyclase. Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), which mediates some of the intracellular events following hormone binding.
G protein-coupled receptors (GPCRs), also known as seven transmembrane receptors, 7TM receptors, heptahelical receptors, and G protein linked receptors (GPLR), are a large protein family of transmembrane receptors that sense molecules outside the Cell and activate inside signal transduction pathways and, ultimately, cellular responses.
Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain coming from the G protein (that was activated by the receptor) via adenylate cyclase and cyclic AMP (cAMP). In a feedback mechanism, these activated kinases phosphorylate the receptor. The longer the receptor remains active, the more kinases are activated, the more receptors are phosphorylated.
Most tissue histamine is found stored in mast cells, where it can be released by a variety of stimuli. Once released, it can cause many effects, including constriction of bronchiolar, gastrointestinal, uterine smooth muscle, and lowering of blood pressure. (Bronchoconstriction, Vasodilation, inflammation, edema)
Etiology (alternately aetiology, aitiology) is the study of causes of diseases.
Pathophysiology- the study how normal physiological processes are altered by diseases.
A hereditary disorder marked by the tendency to develop immediate allergic reactions to substances such as pollen, food, dander, and insect venoms and manifested by hay fever, asthma, or similar allergic conditions.
Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its non-competitive and irreversible inhibition of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Thromboxanes are responsible for the aggregation of platelets that form blood clots.
Cyclic adenosine monophosphate (cAMP)
Protein kinase activation
Cyclic AMP is involved in some protein kinases. For example, PKA (protein kinase A, also known as cAMP-dependent protein kinase) is normally inactive as a tetrameric holoenzyme, consisting of 2 catalytic and 2 regulatory units (C2R2), with the regulatory units blocking the catalytic centers of the catalytic units.
Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus activating the catalytic units and enabling them to phosphorylate substrate proteins.
Cyclic guanosine monophosphate (cGMP)
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (protein kinase G) is a dimer consisting of one catalytic and one regulatory unit, with the regulatory units blocking the active sites of the catalytic units.
cGMP binds to sites on the regulatory units of PKG and activates the catalytic units, enabling them to phosphorylate their substrates. Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory units do not disassociate.
Aminophylline is a drug combination that contains theophylline and ethylenediamine in 2:1 ratio.
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.
Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
Drugs, substances used in medicine either externally or internally for curing, alleviating, or preventing a disease or deficiency.
Pharmacokinetics - what happens to the drug while in the body. Affects target dose level.
Absorption and Bioavailability
Distribution (affected by protein binding)
Metabolization and Elimination
Pharmacodynamics - what effects the drug has on parts of the body. (Membrane action or receptor interaction)
CNS activity (desired or undesired effects)
Psychoactivity (depressant, stimulant, hallucinogenic effects)
A receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand.
Neurotransmitter, chemical that transmits information across the junction (synapse) that separates one nerve cell (neuron) from another nerve cell or a muscle. Neurotransmitters are stored in the nerve cell's bulbous end (axon). When an electrical impulse traveling along the nerve reaches the axon, the neurotransmitter is released and travels across the synapse, either prompting or inhibiting continued electrical impulses along the nerve. There are more than 300 known neurotransmitters, including chemicals such as acetylcholine, norepinephrine, adenosine triphosphate, and the endorphins, and gases, such as nitric oxide. Neurotransmitters transmit information within the brain and from the brain to all the parts of the body. Acetylcholine, for example, sends messages to the skeletal muscles, sweat glands, and heart; serotonin release underlies the process of learning and consciousness.
Some examples of neurotransmitter action:
Acetylcholine - voluntary movement of the muscles
Norepinephrine - wakefulness or arousal
Dopamine - voluntary movement and emotional arousal
Serotonin - memory, emotions, wakefulness, sleep and temperature regulation
GABA (gamma aminobutyric acid) - inhibition of motor neurons
Glycine - spinal reflexes and motor behaviour
Neuromodulators - sensory transmission-especially pain
A white crystalline derivative of choline, C7H17NO3, that is released at the ends of nerve fibers in the somatic and parasympathetic nervous systems and is involved in the transmission of nerve impulses in the body.
A substance, C8H11NO3, both a hormone and neurotransmitter, secreted by the adrenal medulla and the nerve endings of the sympathetic nervous system to cause vasoconstriction and increases in heart rate, blood pressure, and the sugar level of the blood. Also called noradrenaline.
A monoamine neurotransmitter formed in the brain by the decarboxylation of dopa and essential to the normal functioning of the central nervous system. A reduction in its concentration within the brain is associated with Parkinson's disease.
A neurotransmitter's effect is determined by its receptor. For example, GABA can act on both rapid or slow inhibitory receptors (the GABA-A and GABA-B receptor respectively). Many other neurotransmitters, however, may have excitatory or inhibitory actions depending on which receptor they bind to.
Neurotransmitters may cause either excitatory or inhibitory post-synaptic potentials. That is, they may help the initiation of a nerve impulse in the receiving neuron, or they may discourage such an impulse by modifying the local membrane voltage potential. In the central nervous system, combined input from several synapses is usually required to trigger an action potential. Glutamate is the most prominent of excitatory transmitters; GABA and glycine are well-known inhibitory neurotransmitters.
Cyclic guanosine monophosphate 3',5'-GMP, cGMP, cyclic GMP; a cyclic nucleotide that acts as a second messenger similar in action to cyclic adenosine monophosphate but generally producing opposite effects on cell function.
Studies on human lung mast cells established that adenosine could enhance IgE-dependent mediator release in vitro by interacting with cell surface purinoceptors of the A2 subtype. Such a mechanism helped explain the preferential protective effect exerted by xanthines such as theophylline against adenosine-induced bronchoconstriction, which may be relevant to the therapeutic efficacy of this drug class in asthma.
Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a neurotransmitter, hormone, or other substance
The first-pass effect (or first-pass metabolism) is a phenomenon of drug metabolism.
After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. The absorbed drug is carried through the portal vein into the liver.
The liver is responsible for metabolizing many drugs. Some drugs are so extensively metabolized by the liver that only a small amount of unchanged drug may enter the systemic circulation, so the bioavailability of the drug is reduced.
Alternative routes of administration (e.g., intravenous, intramuscular, sublingual) avoid the first-pass effect.
In human anatomy, the hepatic portal system is the system of veins that comprises the hepatic portal vein and its tributaries. It is also called the portal venous system, although it is not the only example of a portal venous system.
The portal venous system is responsible for directing blood from parts of the gastrointestinal tract to the liver. Things absorbed in the small intestine, for example, would be taken to the liver for processing before being sent to the heart. Many drugs that are absorbed through the GI tract are substantially metabolized by the liver before reaching general circulation. This is known as the first pass effect.
In the fields of organic and medicinal chemistry a partition or distribution coefficient is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium. Hence these coefficients are a measure of differential solubility of the compound between these two solvents.
Normally one of the solvents chosen is water while the second is hydrophobic such as octanol. Hence the partition coefficient is a measure of how hydrophilic ("water loving") or hydrophobic ("water hating") a chemical substance is. Partition coefficients are useful for example in estimating distribution of drugs within the body. Hydrophobic drugs with high partition coefficients are preferentially distributed to hydrophobic compartments such as lipid bilayers of cells while hydrophilic drugs (low partition coefficients) preferentially are found in hydrophilic compartments such as blood serum.
pH = pKa + log ([conjugate base]/[weak acid]) or
pOH = pKa + log ([conjugate acid]/[weak base])
Acute: In medicine, an acute disease is a disease with either or both of:
· A rapid onset
· A short but severe course
Chronic (medicine), a persistent and lasting disease or medical condition, or one that has developed slowly.
Inflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for infection. Even in cases where inflammation is caused by infection it is incorrect to use the terms as synonyms: infection is caused by an exogenous pathogen, while inflammation is the response of the organism to the pathogen.
The classic signs and symptoms of inflammation:
· Loss of function
White blood cells or leukocytes are cells of the immune system which defend the body against both infectious disease and foreign materials.
Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing inflammation.
Normal RBC in blood 4.5-5.5 million/cubic mm of blood
Normal WBC in blood 4,000-11,000/cubic mm of blood
Normal platelets in blood 250,000-500,000/cubic mm of blood
Normal Hb in blood Male 16gm, Female 14.5gm/dl
Normal glucose in blood 80-120mg/dl
Leukotrienes are produced in the body from arachidonic acid by the enzyme 5-lipoxygenase in response to inflammation and tissue injury. Leukotriene is a potent bronchoconstrictor and vasodilator.
Epidemiology is the study of distribution of health related states and events in population.
Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.
Inhaled glucocorticoids are the most widely used of the prevention medications and normally come as inhaler devices (ciclesonide, beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone).
Side effects of corticosteroids
Long-term use of corticosteroids can have many side effects including a redistribution of fat, increased appetite, blood glucose problems and weight gain. In particular high doses of steroids may cause osteoporosis. For this reasons inhaled steroids are generally used for prevention, as their smaller doses are targeted to the lungs unlike the higher doses of oral preparations. Nevertheless, patients on high doses of inhaled steroids may still require prophylactic treatment to prevent osteoporosis.
Beclomethasone or Budesonide: 100-400mg twice daily
Fluticasone: 50-200mg twice daily
Beclomethasone or Budesonide: 800-2000mg/daily
Side effects of salbutamol-
Common adverse effects include: tremor, palpitations and headache.
Infrequent adverse effects include: tachycardia, muscle cramps, agitation, hypokalemia, hyperactivity in children, and insomnia.
Salbutamol: 100mg/puff as required
Salmeterol: 50mg twice daily
Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their degradation by PDE. The PDE superfamily of enzymes is classified into 11 families, namely PDE1-PDE11, in mammals. PDE3 is sometimes referred to as cGMP inhibited phosphodiesterase.
Inhibitors of PDE can prolong or enhance the effects of physiological processes mediated by cAMP or cGMP by inhibition of their degradation by PDE.
The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP.
A mast cell (or mastocyte) is a resident cell of areolar connective tissue (loose connective tissue) that contains many granules rich in histamine and heparin. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens.
The parasympathetic nervous system uses only acetylcholine (ACh) as its neurotransmitter. The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of the postganglionic nerve. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.
Muscarinic receptors are those membrane-bound acetylcholine receptors that are more sensitive to muscarine than to nicotine. Those for which the contrary is true are known as nicotinic acetylcholine receptors. Muscarine and nicotine are both alkaloids. Many drugs and other substances (for example pilocarpine and scopolamine) act as agonists or antagonists of only muscarinic or only nicotinic receptors, making this distinction useful.
Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ligand gated ion channels in cells' plasma membranes. Like the other type of acetylcholine receptors, muscarinic acetylcholine receptors (mAChRs), their opening is triggered by the neurotransmitter acetylcholine (ACh), but they are also opened by nicotine.
Cytokine: proteins or chemicals produced by WBC- during immune or inflammatory response.
Chemokine: Any cytokine that cause chemotaxis
Chemotaxis: Movement of WBC in response to cytokine
In biology, Immunoglobulin E (IgE) is a class of antibody (or immunoglobulin "isotype") that has only been found in mammals. It plays an important role in allergy, and is especially associated with type 1 hypersensitivity.
Side effects of theophylline:
o Nausea and vomiting
o Gastric discomfort
Theophylline can also cause nausea, diarrhea, increase in heart rate, arrhythmias and CNS excitation. It has a narrow therapeutic index.
The autonomic nervous system (ANS) is divided into two limbs, the parasympathetic nervous system which is primarily involved in relaxation, and the sympathetic nervous system which causes the body to become more active as in the "fight or flight" response.
Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction.
The parasympathetic nervous system uses only acetylcholine (ACh) as its neurotransmitter.