Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
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Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
Autacoids - pharmacological actions and drugs related to them. SIVASWAROOP YARASI
Autacoids or "autocoids" are biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek "autos" (self) and "acos" (relief, i.e. drug).
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Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
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2. 2
Respiratory Stimulants
1. Activating Respiratory Center Directly:
Caffeine
Bemegride – amp. 0.5% - 10 ml
Etimizol – amp. 1.5% - 3 ml, Tab. 0.1 g
2. Reflex Action:
Cytiton
Lobeline hydrochloride
Ammonia solution
3. Mixed Type of Action:
Cordiamin (Nikethamide) – amp. 1 ml, vial 15 ml
Sulfocamphocaine – amp. 10% - 2 ml
Carbogen (Carbon dioxide)
3. MechanismsMechanisms of Action of Caffeineof Action of Caffeine
1). Blockade of Phosphodiesterase =>
⇑ cAMP and ⇑cGMP
2) Blockade of Adenosine Receptors
ADENOSINE –
an Inhibitory Transmitter of the CNS
inhibits Adenyl Cyclase activity, causing
Contraction of Airway Smooth Muscle
4. Cordiamin (Niketamide) amp. 1 ml, vial 30 ml –
an analeptic of mixed action
Direct Exciting influence on Respiratory Center
Stimulates N-Receptors of Carotid Sinus
•Acceleration and Deepening of Respiration
• HR, BP
Clinical uses:
Respiratory failure in Shock, Collapse, Asphyxia;
Respiratory depression in Infectious diseases;
Prophylaxis of lung atelectasis and pneumonia
Adverse effects: clonic seizures, face hyperemia
5. CarbogenCarbogen – is a mixture of– is a mixture of OO22 93-95%93-95% withwith
Carbon dioxideCarbon dioxide COCO22 5-7%5-7%
It is used in anesthesia for inhalation.It is used in anesthesia for inhalation.
Addition COAddition CO22 to the Oto the O22 =>=> stimulationstimulation ofof
Respiratory CenterRespiratory Center and much better using of Oand much better using of O22
55
6. CLINICAL USE OFCLINICAL USE OF BREATHING STIMULANTS
ACUTE RESPIRATORY FAILUREACUTE RESPIRATORY FAILURE ::
AsphyxiaAsphyxia (Respiratory Arrest)(Respiratory Arrest) of Newbornsof Newborns andand
duringduring surgical operationssurgical operations
Aggravation ofAggravation of Chronic Obturating BronchialChronic Obturating Bronchial
DiseasesDiseases with sleepiness, inability to cough outwith sleepiness, inability to cough out
Respiratory depression duringRespiratory depression during Infectious DiseasesInfectious Diseases
Shock, SShock, Synyncopal conditionscopal conditions
duringduring surgical operationssurgical operations
PoisonsPoisons withwith Hypnotic drugs, Opioid Analgesics,Hypnotic drugs, Opioid Analgesics,
General AnestheticsGeneral Anesthetics
66
7. ANTITUSSIVE DRUGS
I. Central Cough Suppressants:
1. With OPIOID mechanism of action:
Codeine
Ethylmorphine
Dextromethorphan
2. With NON-OPIOID mechanism of action:
Glaucine
Tusuprex
Broncholytin
II. Peripherally acting drugs:
Libexin
Falimint 77
8. CODEINECODEINE ((MethylmorphineMethylmorphine) - an opioid alkaloid) - an opioid alkaloid
Analgesic propertiesAnalgesic properties ––
agonist activity at theagonist activity at the opiate receptorsopiate receptors
AntitussiveAntitussive action –action – a direct suppressive action ona direct suppressive action on
thethe cough centercough center andand mucosal secretion.mucosal secretion.
Delay gastric empting,Delay gastric empting,
PlasmaPlasma AMYLASEAMYLASE andand LIPASELIPASE levels,levels,
Biliary tract pressure resulting from contraction ofBiliary tract pressure resulting from contraction of
the sphincter of Oddi.the sphincter of Oddi.
May produceMay produce DEPENDENCEDEPENDENCE (psychiatric and physical).(psychiatric and physical).
Adverse effectsAdverse effects:: euphoria, hypotension, bradycardia,euphoria, hypotension, bradycardia,
constipation, urine retention, physical dependenceconstipation, urine retention, physical dependence
88
9. TabletsTablets CODEINECODEINE: 0.015 g: 0.015 g
withwith Sodium BicarbonateSodium Bicarbonate
Tablets “Tablets “CODTERPINECODTERPINE”:”:
Codeine 0.015 gCodeine 0.015 g
SodiumSodium BicarbonateBicarbonate 0.25 g0.25 g
Terpine hydrate 0.25 gTerpine hydrate 0.25 g
””Tablets for CoughTablets for Cough”:”:
Codeine 0.02 gCodeine 0.02 g
Thermopsis grass 0.01 gThermopsis grass 0.01 g
SodiumSodium BicarbonateBicarbonate 0.2 g0.2 g
Licorice root 0.2 g.Licorice root 0.2 g.
99
10. 10
Glaucine hydrochloride - Tab. 0.05 -
an alkaloid from plant Glaucium flavum
inhibits the Central Link of
the Cough Reflex.
Broncholytin - Syrup 125 ml –
a complex antitussive drug.
125 ml of syrup contains:
Glaucine 0.125 g
Ephedrine 0.1 g
Basil Oil 0.125 g
11. Libexine - tab. 0.1 g –
a synthetic Antitussive of
Peripheral Action
inhibits the Peripheral Link of the Tussive
Reflex
Anesthesia of Mucous Membrane of
upper Respiratory Tract
Broncholytic properties
1111
12. EXPECTORANTSEXPECTORANTS
I. BRONCHOSECRETOR DRUGS:I. BRONCHOSECRETOR DRUGS:
1. Reflex type of action:1. Reflex type of action:
Thermopsis Grass InfusionThermopsis Grass Infusion
Althaea Root DecoctionAlthaea Root Decoction
2. Resorptive type of action:2. Resorptive type of action:
Potassium IodidePotassium Iodide
Sodium BicarbonateSodium Bicarbonate
MucaltinMucaltin
1212
13. II. Mucolytic Drugs –
convert sticky and viscous sputum to more liquid one and
promote its easier release
1. Activating hydrolytic enzymes in sputum:
Acetylcysteine (ACC) - amp. for inhalation 20%-10 ml,
amp. for injection 10%-2 ml , tab 0.5 mg
2. Activating hydrolytic enzymes and
endogenous Surfactant production:
Bromhexine -Tab. 0.004 and 0.008 g
Ambroxole -Tab. 0.03 g; syrup 0.3%-100 ml
13
14. AcetylcysteineAcetylcysteine ((ACC)ACC)--
anan mucolytic of direct actionmucolytic of direct action
It is administered byIt is administered by
NebulazationNebulazation, PO,, PO,
Direct Application,Direct Application,
or Intratracheal Instillationor Intratracheal Instillation..
1414
15. MECHANISM OF ACTIONMECHANISM OF ACTION::
ACCACC splits thesplits the DISULFIDEDISULFIDE
BONDS of MUCOPROTEINEBONDS of MUCOPROTEINE,,
responsible for increasedresponsible for increased
viscosity of mucus secretions inviscosity of mucus secretions in
the lungs - secretions becomethe lungs - secretions become
less viscous and more liquid.less viscous and more liquid.
1515
16. ACCACC is ais a ParacetamolParacetamol antidote.antidote.
The mechanismThe mechanism::
Restores hepatic stores ofRestores hepatic stores of GLUTATIONEGLUTATIONE
Inactivates the toxic metabolites preventingInactivates the toxic metabolites preventing
Liver damageLiver damage
1616
17. Clinical uses of ACCClinical uses of ACC::
Acute and chronic broncho-pulmobary diseasesAcute and chronic broncho-pulmobary diseases
Tracheostomy careTracheostomy care
Pulmonary complications of surgeryPulmonary complications of surgery
Diagnostic bronchial studiesDiagnostic bronchial studies
1717
18. AmbroxoleAmbroxole andand BromhexineBromhexine ––
are Mucolytic and Expectorant agents:are Mucolytic and Expectorant agents:
=> Depolymerization ofof
MucoproteinesMucoproteines andand MucopolysaccharidesMucopolysaccharides of Expectorationof Expectoration
that induces its liquefactionthat induces its liquefaction
They stimulate production ofThey stimulate production of SurphactantSurphactant ––
endogenous superficially active substance that is producedendogenous superficially active substance that is produced
in alveolar cellsin alveolar cells
NORMALIZENORMALIZE Secretion of Bronchial Glands,Secretion of Bronchial Glands,
IMPROVEIMPROVE reological properties ofreological properties of sputumsputum,,
REDUCE iREDUCE its viscosity,ts viscosity,
RELIEVERELIEVE excretionexcretion ofof sputumsputum from bronchifrom bronchi
1818
19. Potassium IodidePotassium Iodide is an expectorant andis an expectorant and
antihyperthyroid agent.antihyperthyroid agent.
It reduces viscosity of mucus by increasing respiratoryIt reduces viscosity of mucus by increasing respiratory
tract secretions.tract secretions.
In addition it acts directly on theIn addition it acts directly on the TThyroid Glandhyroid Gland to inhibitto inhibit
synthesis and release ofsynthesis and release of Thyroid HormoneThyroid Hormone..
1919
20. Sodium Bicarbonate -Sodium Bicarbonate -
Viscosity of mucusViscosity of mucus
Bronchial secretionsBronchial secretions
2020
22. BRONCHODILATORS
1. Agents stimulating β2– adrenoreceptors of bronchi:
a) Selective β2-adrenomimetics (AMs):
β2-AMs of Short action (4–6 hours):
Salbutamol, Terbutaline, Fenoterol
β2-AMs of Long action (> 12 hours):
Salmeterol, Formoterol
b) Non-selective Adrenomimetics:
Ephedrine, Adrenaline hydrochloride, Isadrin
Orciprenaline sulfate (Alupent)
2222
23. 2. Methylxanthines – Spasmolytics of direct action:
a) Theophylline preparations with short period of action:
Theophylline, Euphylline (Aminophylline), Oxtriphylline
b) Theophylline preparations with long period of action :
Theobilong, Theodur, Theotard, Durophyllin
3. M-cholinoblockers:
Ipratropium bromide (Atrovent)
Tiotropium bromide
Oxitropium bromide
2323
25. SalmeterolSalmeterol andand FormoterolFormoterol --
havehave LIPOPHILICLIPOPHILIC PROPERTIESPROPERTIES
SALBUTAMOLSALBUTAMOL has minor length (has minor length (11 Angstrem11 Angstrem))
andand hydrophilic properties.hydrophilic properties.
It comparatively quicklyIt comparatively quickly ““washes outwashes out”” from receptor’sfrom receptor’s
area and its duration lastsarea and its duration lasts 4-6 hours4-6 hours..
SALMETEROLSALMETEROL is long (is long (25 Angstrem25 Angstrem) molecule and) molecule and
exceedsexceeds SalbutamolSalbutamol in lipophility by dozens times.in lipophility by dozens times.
The long chain is strongly attaching to the cellThe long chain is strongly attaching to the cell
membrane and active center of the drug is capable tomembrane and active center of the drug is capable to
activate receptor repeatedlyactivate receptor repeatedly providing bronchodilationproviding bronchodilation
forfor 12 hours.12 hours.
2525
26. Aminophylline (Euphylline) –
Theophylline 79%
Ethylenediamine 21% complex
Theophylline:
inhibits PDE => cAMP
blocks Adenosine receptors
Anti-Inflammatory action: It inhibits the late response to
antigenic challenge, and
Withdrawal of Theophylline causes worsening of
asthmatic symptoms, a fall in spirometry, and significant
in CD4+ and CD8+ Lymphocytes in bronchial biopsies
2626
27. Clinical uses of EuphyllineClinical uses of Euphylline::
AAsthma, including IV insthma, including IV in
AAcute severecute severe asthmaasthma
CChronic Obstructive Pulmonary Diseasehronic Obstructive Pulmonary Diseasess
AAcute Bronchospasmcute Bronchospasm
LLeft-eft-SSided Heart Failureided Heart Failure
SSevereevere BBronchospasm inronchospasm in IInfantsnfants
2727
28. 2828
Drugs with Anti-Inflammatory Activity
I. Steroid Anti-Inflammatory Drugs (SAIDs) – Glucocorticoids:
1. Natural – Hydrocortisone acetate
2. Synthetic with resorptive action –
Prednisolone, Dexamethasone, Triamcinolone
3. Synthetic with local action –
Beclometasone, Budesonide, Flunisolide, Fluticasone
II. Mast cell stabilizers:
Cromolyn sodium ( Intal -caps for inhalation 0.2 g)
Nedocromil (Nedocromil sodium – aerosol dosed: 2 mg/dose)
Ketotifen (tab. 1 mg)
III. Leukotriene Modifiers:
1. Inhibitors of 5-lipooxygenase: Zileuton
2. Leukotriene Receptor Blockers: Zafirlukast, Montelukast
29. ZafirlukastZafirlukast andand MontelukastMontelukast competitively inhibitcompetitively inhibit
cysteinylcysteinyl Leukotriene ReceptorsLeukotriene Receptors
LeukotrieneLeukotriene BB44 ((LTBLTB44) is a potent neutrophil) is a potent neutrophil
chemoattractant,chemoattractant,
LTCLTC44 andand LTDLTD44 produce bronchoconstriction,produce bronchoconstriction,
mucosal edemamucosal edema
All the leukotriens (All the leukotriens (LTCLTC44, LTD, LTD44 and LTEand LTE44) act on the) act on the
samesame cysteinyl-leukotriene receptorcysteinyl-leukotriene receptor
ZafirlucastZafirlucast andand MontelucastMontelucast relax the airways inrelax the airways in
mild asthma, the bronchodilators activity beingmild asthma, the bronchodilators activity being
one thirdone third that ofthat of SalbutamolSalbutamol..
TheyThey Sputum EosinophiliaSputum Eosinophilia
2929
30. ZafirlukastZafirlukast andand MontelukastMontelukast ––
are not a cure-all for asthmaare not a cure-all for asthma;;
their main use is as add-on therapy for:their main use is as add-on therapy for:
Mild-to-moderate asthmaMild-to-moderate asthma ––
that is not controlled by an ‘as required’
Short-acting β2-agonist + Inhaled GC
Exercise-induced bronchospasm
Aspirin- induced asthma
3030
32. GlucocorticoidsGlucocorticoids - do not relax airway smooth- do not relax airway smooth
muscle directly but:muscle directly but:
Stimulate the synthesis of enzymes needed toStimulate the synthesis of enzymes needed to
Inflammatory ResponseInflammatory Response
NumberNumber andand ActivityActivity of cells involved in airwayof cells involved in airway
inflammation –inflammation – Macrophages, EosinophilsMacrophages, Eosinophils, and, and
T-lymphocytesT-lymphocytes
Suppress the Immune SystemSuppress the Immune System by reducingby reducing
activity and volume of the lymphatic systemactivity and volume of the lymphatic system
3232
33. ADVERSE EFFECT OF GCsADVERSE EFFECT OF GCs
Oropharyngeal Candidiasis –THRUSH
SYSTEMIC EFFECTS:
BP, Edema, CHF,
Thromboembolism,
Thrombophlebitis,
Cushingoid State (moonface,
buffalo hump, central obesity),
Peptic Ulceration,
Increased Appetite,
Muscle Weakness,
Osteoporosis, Hirsutism,
Growth Suppression in Children.
3333