HISTAMINE.

Views:
 
     
 

Presentation Description

histamine and antihistaminics

Comments

Presentation Transcript

HISTAMINE:

HISTAMINE Presented By Toshit sharma M.Pharm (1 st Sem ) Pharmacology

PowerPoint Presentation:

Autos -self Akos -healing remedy AUTACOIDS - these are biologically active substances that act locally at the site of synthesis and release that is with in the inflammatory pockets. AUTACOIDS=LOCAL HORMONES AUTACOIDS

INVOLVEMENT:

INVOLVEMENT Autacoids are involved in various pathological and physiological processes these are- Reaction to injury Immunological reactions Serve as transmitters or modulators in nervous system

TYPES OF AUTACOIDS:

TYPES OF AUTACOIDS AMINE AUTACOIDS - histamine ,5-hydroxytryptamine (serotonin) LIPID DERIVED AUTACOIDS- prostaglandins, leukotrienes,platelet activating factor PEPTIDE AUTACOIDS- angiotensin,plasmakinins (bradykinins,kallidin)

INTRODUCTION :

INTRODUCTION Histamine , meaning tissue amine, I t is an organic nitrogen compound involved in- local immune responses regulating physiological function in the gut and acting as a neurotransmitter triggers the inflammatory response increasing the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues .

PowerPoint Presentation:

Within the human body, the largest histamine concentrations are in the skin, lungs , and gastrointestinal mucosa. Histamine is present in human plasma at relatively low concentrations (usually less than 0.5 ng / mL ); in contrast, whole blood levels can be as high as 30-fold greater. Substantial quantities of histamine are present in urine, with excretion rates varying from 10 to 40 g per 24 hours .

Synthesis and degradation of histamine:

Synthesis and degradation of histamine Histamine is derived from the decarboxylation of the amino acid histadine, a reaction catalysed by the enzyme L-histidine decarboxylase. Once formed, histamine is either stored in granules of mast cells or rapidly degraded by its primary degradative enzymes N-methyl transferase(methylation) and diamine oxidase(oxidation ).

PowerPoint Presentation:

Fig 1- showing synthesis and degradation of histamine

Antigen-Mediated Histamine Release:

Antigen-Mediated Histamine Release

NonAntigen-Mediated Release of Histamine :

NonAntigen-Mediated Release of Histamine Histamine may be released from mast cells by mechanisms that do not require prior sensitization of the immune system these are- Tissue damage, trauma, stings, venoms, proteolytic enzymes, phospholipase A Polymers like dextran,PVP Drugs like-tubocurarine, morphine,atropine,vancomycin. Surface active agents like tween 80 these produce anaphylactoid reaction-itching and burning sensation,flushing,urticaria,fall in B.P, tachycardia and asthma.

HISTAMINE RECEPTORS:

HISTAMINE RECEPTORS

PHARMACOLOGICAL ACTIONS:

PHARMACOLOGICAL ACTIONS Heart H 1 -decreased AV conduction H 2 -increased chronotropy, decreased inotropy H 1, H 2 -increased automaticity

PowerPoint Presentation:

Histamine affects both cardiac contractility and electrical events directly. It increases the force of contraction of both atrial and ventricular muscle by promoting the influx of Ca2+, and it speeds heart rate by hastening diastolic depolarization in the sinoatrial (SA) node. It also acts directly to slow atrioventricular (AV) conduction, to increase automaticity, and in high doses especially,to elicit arrhythmias. With the exception of slowed AV conduction, which involves mainly H1 receptors, all these effects are largely attributable to H2 receptors and cAMP accumulation. If histamine is given i.v,direct cardiac effects of histamine are overshadowed by baroreceptor reflexes elicited by the reduced blood pressure.

PowerPoint Presentation:

Lung H 1 – bronchoconstriction, increased mucus viscosity H 2 - slight bronchodilation, increased mucus secretion H 1 - stimulation of vagal sensory nerve endings: cough

PowerPoint Presentation:

Gastrointestinal System H 2 - acid, fluid and pepsin secretion H 1 - increased intestinal motility and secretions Cutaneous Nerve Endings H 1 - pain and itching

HISTAMINERGIC AGONIST:

HISTAMINERGIC AGONIST NON SELECTIVE ( H 1 +H 2 +H 3 ) AGONIST Histamine, betahistine SELECTIVE H 1 AGONIST 2-Methylhistamine,2-Pyridyl ethylamine,2-Thiazolylethylamine. SELECTIVE H 2 AGONIST 4-Methylhistamine,Dimaprit,Impromide SELECTIVE H 3 AGONIST alpha-Methylhistamine,Imetit

USES-::

USES-: A characterized state of human body by elevated levels of dopamine,serotonin, Norepinephrine , low absolute basophils and low whole blood histamine is called HISTAPENIA. SYMPTOMS Absence of seasonal, inhalent  allergies Multitude chemical or food sensitivities High anxiety and low libido Tendency of paranoia Auditory Hallucinations, hyperactivity, "nervous" legs, and grandiosity

DIAGONOSTIC USES-:

DIAGONOSTIC USES- Sampling of gastric acid content-1mg histamine subcutaneously to stimulate gastric secretion. Pulmonary function for diagnosing asthma Allergy skin prick test control Sensory nerve function

HISTAMINERGIC ANTAGONISTS:

HISTAMINERGIC ANTAGONISTS H 1 receptor antagonist FIRST GENERATION Highly sedative Anticholinergic SECOND GENERATION Non-sedative Non-anticholinergic

PowerPoint Presentation:

H 2 receptor antagonist Ranitidine, cimetidine,famotidine,roxatidine H 3 RECEPTOR ANTAGONIST Thioperamide

PHARMACOLOGICAL ACTIONS:

PHARMACOLOGICAL ACTIONS At therapeutic doses, the 1 st and 2 nd generation antihistaminics are equilibrium-competitive inhibitors of H1-receptor–mediated responses, Certain second generation drugs are noncompetitive inhibitors at high concentrations. Both 1 st and 2 nd generation compounds have negligible abilities to block the H2-,H3,receptors. H1-antagonists generally produce sedation through an effect on the CNS; however, excitation can occur when toxic dosages are ingested. Many of these drugs have effects that are not mediated by H1-receptors the antimuscarinic activity of several first-generation H1-blockers may account for their effectiveness in combating motion sickness and their limited ability to suppress parkinsonian symptoms

PowerPoint Presentation:

Diphenhydramine and promethazine are effective local anesthetics. Many second generation antihistamines also have been found to inhibit the non–histamine-mediated release of various inflammatory substances; this may account for some of their effectiveness in allergic conditions.

PowerPoint Presentation:

Antagonism of histamine - A ntihistaminics blocks- histamine induced bronchoconstriction contraction of intestinal and other smooth muscle triple response-especially wheal, flare and itch. Fall in BP Release of Adr from adrenal medulla in response to histamine Action of histamine on gastric secretion is singularly not affected by these drugs .

PowerPoint Presentation:

Anti-allergic action- Immediate hypersensitivity (type I reactions) are suppressed. Urticaria, itching and angioedema are well controlled. Anaphylactic fall in BP is only partially prevented. Asthma is practically unaffected. In the asthamatic reaction it is now well established that leukotrienes (C4 and CD4) and PAF are more important mediators for human asthma.

PowerPoint Presentation:

CNS Sedation property depend on drugs ability to penetrate blood brain barrier and its affinity for the central(compared to peripheral) H1 receptors. Some individuals also experience stimulant effects like restlessness and insomnia excitement and convulsions are frequently seen at toxic doses. The second generation antihistaminics are practically nonsedating . Preventing motion sickness,it is not certain whether this is due to antagonism of histamine in the brain or reflects antimuscarinic property of these drugs. Promethazine also controls vomiting of pregnancy and other causes.

PowerPoint Presentation:

Promethazine and few other antihistaminics reduce tremor, rigidity and sialorrhoea of parkinsonism. Anticholinergic and sedative properties underlie the benefit. Some H1 antihistamines are also effective as anti-fussives see Ch. 16). Anticholinergic action Many H, blockers in addition antagonize muscarinic actions of ACh. If used concurrently with atropine or its substitutes phenothiazines, tricyclic antidepressants, di-isopyramide, the anticholinergic action adds up.

PowerPoint Presentation:

HIGH LOW MINIMAL/ABSENT PROMETHAZINE CHLORPHENIRAMINE FEXOFENADINE DIPHENHYDRAMINE HYDROXYZINE ASTEMIZOLE DIMENHYDRINATE TRIPROLIDINE LORATADINE PHENIRAMINE CYCLIZINE CETIRIZINE CYPROHEPTADINE MIZOLASTINE Grading of Anti-cholinergic action of H1 Anti-histaminics

PowerPoint Presentation:

Local Anesthesia first-generation H1 antagonists are potent local anesthetics(membrane stablizing property) They block sodium channels in excitable membranes in the same fashion as procaine and lidocaine. Diphenhydramine and promethazine are actually more potent than procaine as local anesthetics. They are occasionally used to produce local anesthesia in patients allergic to the conventional local anesthetic drugs. Membrane stabilizing activity also confers antiarrhythmic property to these compounds

PowerPoint Presentation:

EFFECT OF ANTI-HISTAMINICS ON VARIOUS RECEPTORS EFFECT OF H 1 ANTI-HISTAMINICS ON VARIOUS RECEPTORS

PowerPoint Presentation:

PHARMACOKINETICS The classical H1 antihistaminics are well absorbed from oral and parenteral routes Cetirizine ( C ), loratadine ( L ), fexofenadine (F) excreted mainly unmetabolized form in the urine but F is primarily excreted in the feces Others metabolized in the liver and excreted in urine. They are widely distributed in the body and enter brain,the newer compounds penetrate brain poorly(2 nd generation) Duration of action of most agents is 4-6 hours, except meclizine, loratadine, cetirizine and fexofenadine which act for 12-24 hours or more.. They induce Cyt P450 liver enzymes

PowerPoint Presentation:

1 st Generation Anti-Histaminics Adverse Effects Sedation Dizziness Fatigue Peripheral antimuscarinic effects dry Mouth blurred Vision constipation urinary Retention

PowerPoint Presentation:

Drug interactions : Additive with classical antimuscarinics Potentiate CNS depressants opioids sedatives general and narcotic analgesics alcohol

PowerPoint Presentation:

2 nd Generation Anti-Histaminics Adverse effects In general, these agents have a much lower incidence of adverse effects than the first generation agents. terfenadine (seldane) and astemizole (hismanal) were removed from the market due to effects on cardiac K+ channels - prolong QT interval (potentially fatal arrhythmia “torsades de pointes” )

PowerPoint Presentation:

Drug intraction Erythromycin and ketoconazole inhibit the metabolism of fexofenadine and loratadine Additive with classical antimuscarinics Potentiate CNS depressants opioids sedatives general and narcotic analgesics alcohol

USES:

USES Allergic disorders – Antihistaminics do not suppress AG: AB reactiory but block the effects of released histamine-are only palliative. They effectively control certain immediate type of allergies, e.g. itching, urticaria, seasonal hay fever,allergic conjunctivitis and angioedema of lips,eyelids, etc Pruritides Common cold Antihistaminics do not affect the course of the illness but may afford symptomatic relief by anticholinergic (reduce rhinorrhoea) and sedative actions. The newer nonsedating antihistamines are less effective inthis respect.

PowerPoint Presentation:

Motion sickness Vertigo Cinnarizine is the H1 antihistamine having additional anticholinergic, anti-5-HT,sedative and vasodilator properties which has been widely used in vertigo. It modulates calcium ion fluxes and attenuates vasoconstrictor action ofmany endogenous substances Preanaesthetic medication Promethazine has been used for its anticholinergic and sedative properties.

PowerPoint Presentation:

Cough Antihistaminics like chlorpheniramine,diphenhydramine and promethazine are constituents of many popular cough remdies. They have no selective cough suppressant action but may afford mptomatic relief by sedative and anticholinergic property Parkinsonism promethazine and some other afford mild symptomatic relief in early cases based on anticholinergic and sedative property Acute muscle dystonia Caused by anhdopaminergic-antipsychotic drugs is promptly relieved by parenteral promethazine or hydroxyzine. This is again based on central anticholinergic action of the drugs.

PowerPoint Presentation:

THANK YOU

authorStream Live Help