Respiration GASES & VAPOURS Types of gases: 1- Therapeutic: Oxygen (O2) – Ozone (O3) – Carbon dioxide (CO2) – Helium 2- Noxious: Carbon monoxide (CO) – Hydrocyanic acid OXYGEN THERAPY Uses of O2: 1- Treatment of Hypoxia (as in bronchial asthma , COPD & anemia) 2- As a diluent for inhalation anesthesia Side effects of O2: 1. Oxygen apnea 2. Retrolental fibroplasias in preterm neonates 3. Pulmonary atelectasis due to bronchial obstruction. --------------------------------------------------------------------------------------------------------------- Uses of Hyperbaric O2: 1- Anaerobic infections 2- Air embolism & Decompression sickness 3- Burns 4- Bone infections 5- CO poisoning 6- Cyanide poisoning ------------------------------------------------------------------------------------------------------------- Ozone (O3) Therapy: - Ozone Therapy is the most powerful of the oxygen therapies as ozone is more strongly oxidizing - Uses of Ozone: 1- Anti-infective against bacteria, fungi & viruses 2- Antineoplastic 3- Ozonated olive oil (Topical) is used in: dry skin, Wrinkles & sunburns 4- Ozonated lemon juice (Topical or Drinking) is used in: cancer skin, psoriasis & ulcer 5- Ozonated water is used in (Drinking): Alzheimer disease, allergy & cancer 6- Oxidizes toxins & chelates heavy metals - Methods of application: 1- Injection 2- Insuflation into ear, vagina or rectum 3- Inhalation: bubbled through olive oil 4- Ingestion of ozonated water 5- Topical through bagging, body suit, ozonated olive oil or steam sauna 102 Respiration Cyanide poisoning - Sources of cyanide: Cyanide is found in insecticides, rodenticides, metal cleaners (silver polish) & photographic solutions and may be released from combustion of nitrogen-containing plastics - Effect & toxicity of Cyanide: Cyanide has high affinity to bind with F+++ of cyto-chrome oxidase enz. (mitochondrial enz. responsible for tissue respiration) leading to histotoxic hypoxia & death within 5 min. - Treatment of Cyanide posoning: -Na Nitrite IV Na Thiosulphate IV -Methylene blue IV Treatment -Amyl Nitrite Inhal. (Tissue rodenase) -Ascorbi a. IV Blood Hb Met-Hb Cyan-Met-Hb Met- Hb Hb (Fe++) (Fe+++) (Fe+++) (Fe++) Cytochrome oxidase Tissues +++ (Fe ) + Cyanide Treatment 1) Long method: 1. Na Nitrite (IV) or Amyl Nitrite (inhalation): convert haemoglobin (Fe++) to met – Hb [Fe+++] – met. Hb + cynide non-toxic cyan–met - Hb Rhodenase 2. Na thiosulphate (I.V) + cyan- met- Hb e n z Na thiocyanate (excreted in urine) + met. Hb. 3. Methlyne blue or vit. C (I.V): reduce met Hb to Hb. 2) Short method 1. Hydroxocobalamine (I.V): chelate cyanide Cyanocobalamine (Vit B12) 2. Dicobalt edetate (I.V): chelate cyanide 103 Respiration COUGH THERAPY Types of cough: 1- Dry [Un productive – Useless] cough: ttt by Antitussives 2- Productive cough: which may be: • Effective (secretion easily expelled) • Ineffective (secretion present but difficult to expel) ttt by Expectorants ± Mucolytics (1) Anti- tussives [Cough supressors] A) Peripheral anti- tussive: B) Central anti- tussives: 1. Demulcents [Liquorice] 1) Narcotic 2. Water steam inhalation ± Tr. Benzoin 1- Highly addicitive h secr. a-Morophine 3. Drugs with local anesthetic activity b-Dihydromorphin [Benzonatate]: c-Heroin It has dual mechanism d-Methadone • Centrally i cough center 2- Less addictive • Peripherally i cough [stretch] a-Codeine receptors b-Dihydrcodeinone c-Pholcodine 2) Non- narcotic 1- Opiate derivative: a- Narcotine b- Dextromethorphan 2- Non- opiate derivative: a- Benzonatate b-Carmiphen [antiparkinsonian] c- Diphenhydramine [H1 blocker] d- Oxeladine (2) Mucolytic agents They liquefy viscid secretions & facilitate the action of expectorants [they are not expectorants] Used in acute & chronic bronchitis. Examples: 1. Bromhexine (Bisolvon): deploymerization of mucopolysaccharides of ground substance of sputum. MP S S MP 2. Ambroxol: is an active metabolite of Bromhexine 3. Carboxymethylcysteine: break the disulphide bonds (s-s) in mucus i surface tension 4. Acetyl cysteine: MP MP • As carboxmethylcysteine S S • Uses: - Inhalation in bronchitis - orally to ttt hepatotoxicity induced by Paracetamol. 104 Respiration (3) Expectorants (Protussives) Example: Guaiacol (Guaifensin) Uses: acute ineffective productive cough Side effects: GIT disturbances – Drowsiness BRONCHIAL ASTHMA Definition: “ Hypersensitivity & Hyper- responsiveness of the bronchi associated with inflammatory changes leading to wide spread narrowing of them” symptoms: - Episodes of triad: Cough – Dyspnea - Wheezes - Between the attacks the pt. may be asymptomatic Physiology: 1) Para symp. nerve A.ch M2,3 Broncho-spasm & hsecretions 2) Symp: nerve N.A α V.C & i secretions Adrenal medulla adrenaline Non- innervated B2 Bronchodilatation 3) Most autacoids Broncho-spasmp except: PGE2 & V.I.P 4) ATP Bronchodilatation A.C + B-agonist + c.AMP Bronchial Tone Theophyllin PDE - A.ch. Adenosine AMP + + - - Bronchoconstriction M-antagonist Theophyllin 105 Respiration Pathogenesis Rexposure YY Exposure to Allergen Mast cells Ig.E Lymphocyte Release of preformed mediators Synth. & release of newly formed mediators - Histamine - PGs - Esinophil chemotactic factor - Leucotreins (LTC4 & LTD4 ) - Neutrophil chemotactic factor - Platelet activating factor (P.A.F) Bronchoconstriction Chemotaxis (Early Reaction) Esinophils Neutrophils + Other mediators 1- Bronchoconstriction 2- Edema & Cellular infiltration 3- Mucous secretion (Late Reaction) 106 Respiration Management of Bronchial asthma 1-General: 1) Advice change the jop 2) Avoid 1. Antigen exposure – smoking - stress & emotions 2.severe excercises 3.the following drugs: * N.S.A.I.Ds allow only paracetamol * Non- selective blockers allow only selective 1 blockers * Parasympathomimetics Bronchospasm * Parasympatholytic: Atropine Dry secretions allow only Ipratropium. * Histamine & histamine releasers * Anti histaminics (1st generation as they have atropine like effect) * Brabiturates i Respiratory center (R.C) * Morphine i R.C, i cough center & it is a histamine releaser * Ether, thiopentone & cyclopropane general anesthesia allow only Halothane 3) ttt: 1.Any chest infection 2.Immunotherapy: hyposensitization 2-Drug therapy of B.A 1) Broncho – dilators: 1- Sympathomimetic: B2 agonist (short acting [SABA] & long acting [LABA]) 2- Parasympatholytic (Anticholinergics): Ipratropium - Tiotropium 3- Methyl xanthines: Aminophylline 4. Other drugs: 1- PGE2 2- (NO) Nitric oxide donors 3-K+ channal openers as (cromokalim) 4-Ca++ channal blockers 2) Anti- inflammatory: 1- Mast cell stabilizers: Disodium cromoglycate (Cromolyn) (Intal) - Ketotifen 2- Cocticosteroids. 3- Anti leukotriene drugs: 1- Zileluten 5- lipo – oxygenase enz. inhibitor 2- Zafirlukast & montelukast leukotriene [LTD4] receptor antagonist • given orally in prophylaxis of B.A • S.E: h serum liver enz. – HME inhibitor - vasculitis – Headache 3) Immunoglobulin antagonists: Anti- IgE monocolonal antibodies Omalizumab (Xolair) 4) Adjuvant drugs: 1. Mucolytic & Expectorants 2. O2 NB.: Anti-asthmatic drugs, now, are clasified into: 1. Quick-relief (rescue) medications: SABA - Systemic steroids - Anticholinergics - Aminophylline 2. Long-term (controller) medications: LABA – Long acting methylxanthines – Antiinflamatory drugs - Anti- IgE 107 Respiration Sympathomimetics Mechanism of action: 1) h B2- receptors : (it is a Gs-receptor) h A.C h c.A.M.P 1.Broncho dilatation 2.i Bronchial secretion 3.Mast cell stabilization 2) h α receptors V.C Decongestion & i edema Members: (see before) 1) Non – selective: serious cardiac side effects - Adrenaline : (S.C & inhal.) - Isoprenaline : (S.C & inhal.) - Ephedrine : (orally) 2) Partially selective B2- agonist: some cardiac side effects - Orciprenaline (Metaproterenol) inhal.& oral. 3) Selective B2 agonist: a- Salbutamol(Albuterol) (ventolin): Oral -I.V- Inhalation (1-2 puffs / 4h [100 g / puff]) b- Levalbuterol, Terbutaline, Salmetrol (servent), Formoterol (foradel), Fenoterol (berotec) • Side effects of selective B2 agonist: Nervous Tension / Tachycardia /Tremors / Tolenance/ Locked lung syndrome Muscarinic Antagonists [Ipratropium & Tiotropium] Mechanism of action: competetive block of muscarinic receptors prevent bronchospasm induced by A.ch as aresult of vagal stimulation. Advantages over atropine: 1. Does not cause dryness of bronchial secretions. 2. Dose not i mucociliary clearance of bronchial secrection 3. No C.N.S action or systemic anticholinergic effect (as it’s a quaternary ammonium) Clinical use: by inhalation 1. In patients with Chronic obstructive pulmonary disease (C.O.P.D) esp. eldery patient 2. Adjuvant to B2 agonist in acute severe asthma 3. When B2 agonist & Theophylline are contraindicated as in thyrotoxicosis NB.: Tiotropium: as Ipratropium, but long acting used once daily 108 Respiration Methyl-xanthines Mechansim of action: 1) i [P.D.E] enz h c.A.M.P • Broncho dilatation • i bronchial secretion • mast cell stabilization 2) competetive block of adenosine receptors • Broncho dilatation • i release of histamine • h release of catecholamines: [due to block of presynaptic receptor] 3) improve diaphragmatic contractions. Uses in Bronchial asthma 1. Acute attack (250 – 500 mg slow I.V) as 2nd line drug in addition to steroids afte r failure of B2 agonist 2. Status asthmaticus: - slow I.V or I.V infusion 6 mg / kg over 30 min. as loading dose, then 0.7 mg / kg / h as maintenance. 3. Prophylaxis: - oral slow release [SR] 200 mg / 12h. - rectal suppository every night 500 mg. Side effects: