cardiovascular and respiratory system Flashcards
Respiratory antiinflammatory groups
- Inhalational glucocorticoids
- Chromones
- Leukotriene antagonists
Inhalation glucocorticoids:
- effects
- Other aplication
- examples
Most effective antiinflammatories
- Inhibition of the expression of several genes decreasing citokine production: IL 4, IL 5!
- Decreased mucous production! Increasing diameter
- Systemic application possible but: several side effects (HTHP axis, stomach, liver etc.)
beclomethasone, fluticasone
chromones are:
how to administer?
mast cell stabilizers
Per os, inhalation, nasal spray, eye drop
Leukotriene synthesis inhibitor
zileuton , (fenleuton)
Leukotriene antagonists
zafirlukast, montelukast (afainst feline asthma)
pranlukast
Peripherial antitussives
mucolytics, expectorants
bronchodilators
coating substances
local anesthetics
Central antitussive
morphine derivatives
antitussitives
- drugs
Codeine, morphine
Dihydrocodeine (more effective, Ø cat!*)
Hydrocodone
Butorphanol (most effective, but ….sedation)
Tramadol
Dextrometorphan (safe also in cats)
Mucolytic — expectorant:
- indications
bronchitis, bronchopneumonia, tracheitis, rhinitis,
sinusitis, RAO as adjunctive therapy
Mucolytics
- drugs
- effects
- admin
N Acetylcysteine (breaks disulphide bonds of the mucoproteins) bad taste and odour - Given per os or inhalation
Carbocystein
- similat action
- oral absorption a little better
Antidote for parecetamol
N Acetylcysteine
Expectorants:
- effects
- drugs
- directly on the mucous membrane of airways , or indirectly by stimulating gastric mucous membrane
Bromhexin Ambroxol Dembrexine (Eq longer half-life) Guaifenesin (Can be combined with antitussives) Ipecacuanha volatile oils Salts (pl. NH 4 Cl, NaI)
Drug groups used for immunosupression:
-examples
- Antimetabolites (Azathioprine, mycophenolate
mofetil, Methotrexate) - Alkylating agents (Cyclophosphamide)
- Glucocorticoids
- Cytokine gene expression inhibitors
- Calcineurin (Cyclosporin and tacrolimus)
Cyclosporin use
per os or oral admin - Autoimmune diseases pemphigus , lupus , AIHA, KCS= keratoconjunctivitis sicca - Atopic dermatitis - IBD
causes arrythmia, dysrythmia:
Ectopic impulse! (impulse...) Cardiomyopathy Re-entry Drugs Electrolite imbalances Primary cause
Quinidine effects
- admin
- side effects
- Vagal effect (+direct effect!)
- Negative inotropic (heart failure!)
- Dog (GI and CV side effects), cat (short t1/2) ??
- Horse IV. or PO.
- frequent side effects
- supraventricular arrhytmias
Sodium channel blockers
Quinidine Procainamide lidocaine Mexiletine Carvedilol flecainide
Procainamide:
- side effects
Side effect (IV.)
- negative inotropic, arrhytmogenic
- Unfavorable pharmacokinetics (short t1/2)
- Ventricular arrhytmias IV.: if refractory to lidocaine
Lidacaine:
- use
- side effects
- admin
- Immediate treatment of life threatening ventricular arrhytmias!
- NO Supraventricular effect
- Advantages
Short t1/2
Damaged cells normal cells
hypocalemia reduces effect - side effects in cats!
- Use diazepam against CNS side effects
Ø negative inotropic effect, hypotension, conductance failure = safe to use - given IV
Oral substitute for lidocaine
Mexiletine
= treatment of ventricular arrhytmias at home
given oraly
- Frequently combined with β-blockers (atenolole, sotalole)
Beta blockers:
1st generation:
2nd generation:
3rd generation:
- Beta 1+2 (Propranolol)
- Beta 1 (Metoprolol, Atenolol, esmolol)
- Ca: in combo with mexiletine
- Beta 1+ peripheral+++ (Carvedilol)
Contraindications for beta blockers
severe bradycardia, AV block
K channel blockers:
- use
- drugs
ERP increases!
excellent in re entry!
Sotalol (boxer cardiomyopathy)
Amiodarone (supraventricular, ventricular)
Ca channel blockers:
- effect
- types of drugs
SA and AV node—-> bradycardia
mainly supraventricular
Decreased Ca2+-influx: decreased contraction and vasodilatation!!
- reducing afterlad
Dihydropyridine type (vessels): amlodipine, nifedipine Non-dihydropyridine type (heart): verapamil, diltiazem
Treatment for Congestive heart failure (CHF):
- types of treatment
- example drugs
- Increasing frequency: only in life threatening cases!
e.g. epinephrine: positive inotropic, chronotropic
increases myocardial oxygen demand - Increasing contractility: digitalis glycosides
- Decreasing preload and afterload: ACE inhibitors
- Inodilators (2+3): PDE inhibitors
- Vasoactive substances (arterial and venous vasodilators): e.g. nitroglycerine
- Diuretics: decrease preload
What is Pimobendan?
contraindications:
PDE inhibitor
Ca2+ sensitizer —> positive inotropic effect
PDE inhibition —> arterial and venous vasodilation
= „INODILATOR”
- Extensive protein binding!
- outflow obstruction
Most important ACE inhibitor:
Benazepril (excreted in urine and bile = good for kidney damage pateints)
Name the ACE inhibitors:
captopril Enalapril Ramipril Benazepril Lisinopril
Angiotensin II receptor antagonists
Losartan, valsartan, telmisartan
Types of diuretics:
- Cardial diuretics
Digoxin
Xanthine derivatives (coffeine, theophyllin, theobromine)
ACE inhibitors - Osmotic diuretics
- Natriuretics
Osmotic diuretics:
- drug
- indications
- admin
- Mannitol (mannit)
only IV as it cant cross menbranes
retains blood in bloodvessels and drain tissues
Indications:
life threatening edemas
acute renal failure (oliguria, anuria)
gleucoma
0,5-1 mg/kg IV. (4-6 h)
- Glycerine
Natriuretics groups:
- Functions
- Examples
- Carboanhydrase inhibitors (inhibit Na/H pump)
- against glaucoma (aquous humor is formed)
- Acetolamide orally, dorsolamide eye drops - Loop diuretics (Na/K pump is inhibited)
- MOST EFFECTIVE DIURETIC!
- Mg2+ and Ca2+ excretion increased
- FUROSEMIDE (oedema! give also if mannitol is not working), torsemide, etacrinic acid - Thiazides
NCCT inhibition –>Na+ and water excretion
K+ excretion increased, Ca2+ excretion decreased!
- Chlorothiazide, Hydrochlorothiazide
- can be given in combo with furosemine to enhance it
4. Potassium sparing diuretics
(ENaC and Na/K-ATP-ase protein expression)
A. Amiloride, triamterene
B. Aldosterone antagonists
*competitive antagonists
* increased Na+ excretion (mild), K+ excretion (mild)
*very mild diuretics!!!
-Spironolactone
Which treatment can you use against allergic conjunctivitis?
- Mast cell stabilizers
- Vasoconstrictors
- Antihistamines (together with 1)
Mast cell stabilizers:
Sodium chromoglycate , lodoxamide, nedocromil
Vaoconstrictos used for allergic conjunctivitis:
Tetryzoline HCl
Antihistamines:
Azelastine, olopatadine , epinastine , emedastine
antazoline
Which drug can be used against the CNS symptoms in lidocaine treatment?
Diazepam
Beta-blockers
- indications
- contraindications
Indications
1. Supraventricular and ventricular arrhytmias
preventing sudden death
2. HCM (too thick heart muscle, = hypertrophic cardiovascular myopathy)
3. Hyperthyroidism, methylxanthine poisoning
Contraindications: severe bradycardia, AV-block
Vaughan-Williams conductance groups: 1. 2. 3. 4. 5.
Antiarrythmia drugs:
1. Na-channel blockers (“membrane-stabilizers”) Quinidine, Procainamide, lidocaine, Mexiletine
2. Beta receptor blockers
Propranolol, Metoprolol, Atenolol, esmolol, Carvedilol
3. Potassium channel blockers
Sotalol, Amiodarone
4. Calcium channel blockers
amlodipine, nifedipine, verapamil, diltiazem
5. Other substances
- Digoxin, atropine
ERP=?
ERP= effective refractory period
The amount of time in which the cell cannot respond to a new conducted stimulus
Congestive heart failure (CHF):
types and causes:
Acute heart failure
cause: sudden deterioration of heart pump function (e.g. myocardial infarction, ventricular fibrillation)
Chronic heart failure
cause: gradual and slow deterioration in heart pump function and performance
Cardiotonics
-used in case of? drug examples
Positive inotropic drugs, cardiotonics In acute heart failure Epinephrine Dobutamine Dopamine
In chronic heart failure
Digitalis glycosides
Pimobendan
Cardiotonics
-Pharmacological effects
1. direct cardiac action positive inotropic: cardiac output increase improves RBF: water and Na+ excretion 2. increases vagal tone negative chronotropic negative dromotropic
Digoxin
pharmacokinetics
Digoxin pharmacokinetics orally protein binding: interactions! accumulation in myocytes measuring plasma levels after 3-5 days excretion via kidney small therapeutic index (hypokalaemia!)
Digoxin side effects:
cardiac: arrhythmias, bradycardia, hypokalaemia!
extracardial: GI-signs (vomiting)
Digoxin
- Usage
- contraindications
Digoxin usage:
prolong survival time in heart failure
supraventricular tachyarrhytmias
Contraindication outflow obstruction (HCM, stenosis)
PDE inhibitors =Phosphodiesterase inhibitors
- effects
- Pimobendan
Pimobendan
- effect
- contraindications
- bioavailability
- side effects
Pimobendan:
- positive inotropic effect
- Ca2+ sensitizer: positive inotropic effect
- PDE inhibition: arterial and venous vasodilation
Contraindications: outflow obstruction
Side effects: Gastrointestinal: diarrhea and appetite
depresion
- give it with feed—> good bioavailability
ACE inhibitors
- indications
Indications
heart failure (species!)
hypertension
proteinuria
ACE inhibitors
- side effects
azotaemia
hypotension: tiredness, faintness!
GI-disturbances: anorexia, vomiting, diarrhea
Ho: dry cough
Angiotensin II receptor antagonists
- advantages
- examples of drugs
Advantages
more effective
no bradykinin activation
Losartan, valsartan, telmisartan
Nitroglycerin :
- effect
- Application
- Pronounced arterial and venous dilation
- dilation of mesenterial veins: „shift” from pulmonary circulation
- Decreased preload, afterload, myocardial O2 consumption!!
- Dilates coronary arteries
-Application: first pass effect orally
IV., sublingual, transdermal patch, ointment—> quick effect —> acute heart failure of decompensated chronic heart failure
Asthma is a complex disease characterized by:
- airway inflammation which leads to airway
hyperresponsiveness which causes symptomatic
bronchoconstriction
=obstructive lung disease and inflammatory disease
COPD is caused by:
an abnormal inflammatory response to an inhaled
environmental insult
- divided into two frequently overlapping diseases emphysema (=alveolar enlargement) and chronic bronchitis (=chronic cough)
Drugs Acting on the Respiratory System:
- Bronchodilatators
- Respiratory antiinflammatory drugs
- Antitussives
- Mucolytics, expectorants
Bronchodilators indications:
- anaphylaxis
- allergic bronchitis
- asthma (Fe), RAO (horse)
- pulmonary edema
- pneumonia
- pleural effusion
- pneumothorax
- tracheal collapse and hypoplasia?
Bronchodilator groups:
- examples
= Act mainly on β 2 adrenergic receptors
- Sympathomimetics
- non specific: Adrenaline, Isoproterenol, Ephedrine
- specific: salbutamol, terbutaline, clenbuterole, salmeterol (= β 2 receptor agonists) - Anticholinergic substances
- Xanthine derivatives
β 2 agonists characteristics:
- side effects
- contraindications
- action time
- Bronchodilators at β 2 receptors (+ variable β 1 receptorial effect)
- SE: tachycardia, restlessness, tremors, decreased uterine contraction
- contraindications: congestive heart failure
- decreased mast cell degranulation
Short acting (1 4 hours) Long acting (6 12 hours)
salbutamol:
- admin
Short acting β 2 agonist
- significant veterinary experience
- given per os or inhalation
terbutaline:
- Specificity
- admin
- used in:
Long acting β 2 agonists
- less specific
- subcutaneous, intravenous injection, inhalation
- feline asthma, organophosphate toxicosis, horse ROA
clenbuterole:
- Specificity
- used in:
Long acting β 2 agonists
- less specific
- less effective in companion animals
- frequently in horse (Ø meat producing animals)
salmeterol:
- specificity
- duration
Long acting β 2 agonists
•most specific (50000:1)
- longest duration
- most expensive
Side effects of bronchodilators:
- β 1: Tachychardia, arrhythmias from ephedrine, isoproterenol
- β 2: skeletal muscle tremor
- α: vasoconstriction and hypertension
- tachyphylaxis
Acetylcholine antagonists (M3 receptors)
- effects
- indications:
Acetylcholine antagonists (M3 receptors)
- bronchodilation + decreased mucous secretion
side effects: tachycardia, mydriasis, decreased
„mucociliary clearence”, paralytic ileus (Eq)
indications:
asthma (Fe!)
horse RAO
organophosphate toxicosis
Bronchodilators, Parasympatholytics:
name the drugs:
- Atropine (in organophosphate toxicosis++)
- Glycopyrrolate (longer action, much safer)
- Ipratropium (quaternary amin, only inhalasol= safe,
does not cross BBB)
-
Methylxanthine derivatives:
- names
- effects
- pharmacokinetics
- side effects
- indications, administration
Caffeine, theobromin
theophyllin:
1. phosphodiesterase inhibitor (bronchodilation)
2.Various pharmacological effects!
3.Pharmacokinetics : good absorption, enterohepatic circulation
4.Side effects : small therapeutic index! (CV, GI, diuresis)
5. Indications, dosage:bronchitis, pneumonia etc.
IV., PO (retard tablets)
Derivatives of theophyllin=
- aminophyllin
- propentophyllin:
- –> bronchodilator
- –> vasodilator: brain, muscles, kidney
- pentoxyfillin
Methylxanthines:
- Therapeutic uses
- Side effects:
- Treat acute or chronic asthma that is unresponsive to
β-adrenoceptor agonists - Treat COPD and emphysema
- Side effects:
arrhythmias , nervousness , vomiting and
gastrointestinal bleeding
In case of digoxin overdose you can give:
Lidocaine
Inodilator definition
inodilators are agents with inotropic effects that also cause vasodilation leading to decreased systemic and/or pulmonary vascular resistance
Positive inotropic effect definition
Positively inotropic agents increase the strength of muscular contraction
Positive chronotropic definition
Positive chronotropes increase heart rate; negative chronotropes decrease heart rate
Why do you take blood samples after 1 week of ACE inhibitor treatment?
To look for azotaemia
=characterized by abnormally high levels of nitrogen-containing compounds
Carboanhydrase inhibitors
- Indications
- side effects
Indications
congestive heart failure
glaucoma (systemic local)
alkalizing urine! (cystine stones)
Side effects
metab. acidosis, other uroliths
Acetazolamide, dorsolamide
Furosemide
- indications
- side effects
Indications
heart failure (primary drug!)
edemas
oliguria, anuria (rehydration!)
Side effects
hypokalemia, hypomagnesemia, metabolic alkalosis, hypotension (Fe), ototoxicity
Indications
1-5 mg/kg iv., im., po.
give 3 times a day against any type of oedemas
Human dosage =much lower!
Combinations –> „aldosteron escape “ NB remodeling, so give together with aldosterone antagonist
Hydrochlorothiazide
- indications
- side effects
Indications heart failure, hypertension Ca oxalate urolithiasis diabetes insipidus Side effects hypokalemia, metabolic alkalosis
Spironolactone
- indications
- side effects
Indications
antagonising aldosterone in CHF!
preventing diuretic induced „aldosteron-escape”
hyperaldosteronism
Side effects
hyperkalemia: don’t use!
Combined treatment of CHF
- dog
- cat
Dog
Pimobendan+furosemide+spironolactone
ACE inhibitor+furosemide+spironolactone
Cat:
- Furosemide
Treating hypertension
Amlodipine+ACE inhibitor
Receptors for bronchocontriction
- cause of bronchoconstrinction
Express muscarinic receptors,especially the excitatory M3 subtype of muscarinic receptors. Upon stimulation, these receptors induce bronchoconstriction.
Acutely, mast cell degranulation produces
bronchoconstriction and airway inflammation
- Mast cells also release leukotriene C 4 (LTC 4) which is
subsequently converted into LTD 4 and LTE 4 —> Bronchoconstriction
Bronchodilation and constriction drugs:
Dilation:
cAMP
(β 2 agonists, xanthine derivatives)
Constriction:
Acetylcholine
Treatment of allergic bronchitis, RAO and
feline asthma:
- Horse treatment combinations
1. Glucocorticoids •continously - beclomethasone, fluticasone 2. Bronchodilators continously or occasionally advantage!
- Other agents in feline asthma:
1. Antihistamines
•cyproheptadine
2. Na chromoglycate
3. Leukotriene antagonists
E.g. HORSE
beclomethasone+salmeterol
beclomethasone+ipratropium
CAT
fluticasone + salbutamol/etc.
Codeine vs morphine:
better bioavailability orally 10 times lower analgesic potency similar antitussive rare side effects - cat!: excitation, convulsions, sedation, constipation
Bromhexin
- actions
- indications
- admin
= Expectorant 3 actions: 1. breaking up mucopolysaccharides, dissolving mucus 2. increasing secretion of serous glands 3. enhancing ciliary movement Enhancing permeation of Igs and AB s! IgA, IgG levels increased - Indications: rhinitis, sinusitis, tracheobronchitis (but: purulent discharge!)
- Side effects: nausea, rash, vomiting, diarrhea,
- per os, sc . BID
