Pharmacology of Muscle Relaxant & Ancillary Drugs Flashcards
What are the main anticholinergics?
Atropine
Glycopyrrolate
Anticholinergics are used to
increase HR, & aim to increase BP
Anticholinergics produce competitive antagonism of
Acetylcholine at the post-ganlionic muscarinic receptrs of the parasympathetic system
Especially the vagus n. –> parasympathetic
What are the pharmacodynamics of anticholinergics
- tachycardia
- bronchodilation
- decreased salivation
- decreased bronchial secretions
- mydriasis
- GI stasis
- decreased lower oesophageal sphincter tone
Atropine
Onset, Duration, Cautions, contraindications
Onset: 1-5 min
Duration: 20-40 mins
Cautions: atropinase in rabbits keeps from working, GI stasis so caution in horses, tachyarrhythomogenic, hypoxaemic, paradoxal transient bradycardia
Contraindications: pre-existing tachycardia, hyperthyroidism, phaeochromocytoma
Glycopyrrolate
Onset, duration, Cautions
- Onset: about 5 mins
- Duration: 1-2 hrs
- Cautions: Do not use CPR, bradycardia & hypotensive
Mixed inotropes & vasopressor sympathomimetics
Dopamine, adrenaline, noradrenaline, ephedrine
Positive inotrope sympathomimetic
Dobutamine
Vasopressors
Phenylephrine
Vasopressin
alpha-1 receptors are on…
vascular smooth muscle
Vasopressors work on what receptors?
alpha-1
Beta-1 receptors are in the…
heart
inotropes act on…
beta-1 receptors in the heart
beta-2 receptors are in the
bronchi, vascular smooth muscle, uterus, heart
bronchodilators work on…
the beta-2 receptors
beta-3 receptors are present on
adipose tissue
Dopamine at low rates act on…
D1 receptors
Dopamine is a precursor to…
noradrenaline & adrenaline
Dopamine best given as a
CRI
Dopamine has what proprerties
- dose-dependent effects
- increases BP
- low doses of D1 pulm receptors
- beta/alpha receptors lead to vasoconstriction
What are the properties of Adrenaline/Epinephrine?
- Endogenous
- Stimulates both α & β receptors
- Dose dependent (higher doses: α effect)
- Bolus/CRI in Farm animals – to increase BP
- Chronotrope (HR ↑), inotrope, & vasoconstrictor
- Bronchodilation (β2 effect)
- Reserved for life-threatening situations
- Anaphylaxis
- Severe hypotension (sepsis)
- Risk of arrhythmias - Decreased threshold for V-fib depending on the dose
Noradrenaline/Norepinephrine
- Endogenous
- Agonist α1, α2, β1 agonist
- Powerful vasoconstrictor
- Use? Patients extremely vasodilated (septic, endotoxaemia) –> inability to vasoconstrict, used to gain normal tone of the vessels
- BP monitoring – must use w/ arterial catheter & arterial BP monitoring
- May cause tissue necrosis
- Arrhythmogenic effect like adrenaline (monitor ECG & BP)
- Reduces perfusion of kidney, liver
- Concomitant use of dopamine to vasodilate on the dopernergic receptors (?)
Ephedrine
- not endogenous
- stimulates release of endogenous noradrenaline (tachyphylaxis)
- short-lived
- tachycardia/bradycardia may occur
- less profound effect than noradrenaline
- decreases renal blood flow & GFR falls
- vasoconstriction & positive inotropic effect
- can be used as bolus, may be used as CRI
Dobutamine
- Acts on contractility
- non-selecctive beta receptor agonist
- predominantly B1 effects
- synthetic analogue of dopamine
- no change in vascular resistance, just changes contractility
- short-acting (CRI req’d) - up to 5 mins
- increases SV
- Metabolised by COMT, urine excretion
- common in horses
Phenylephrine
- A1 agonist
- vasoconstriction
- more potent than noradrenaline
- reflex bradycardia
- uses: hypotension, nasal oedema in horses, splenic contraction in horses
- Special license req’d in IE for small animals so not really used
Vasopressin (ADH)
- not available in IE
- stimulates release of catecholamines from adrenal medulla
- increases contractility
- used in CPR in humans & refractory hypotension
- expensive
Bronchodilators tend to work as
beta2 agonists
Bronchodilators are primarily administered in
aerosol form due to faster onset of action
Bronchodilators can cause
tachycardia at high doses due to B1 activation
Bronchodilators are primarily used for…
- asthmatic airways or things that require bronchodilation
- hypoxaemic horses
Salbutamol
- relaxes bronchial smooth muscles
- reverses hypoxic pulmonary vasoconstriction
- causes tachycardia
- relaxes gravid uterus
- may cause tremor
- decreases K+ at Na/K ATPase
Terbutaline
- injectable form used prior to bronchoscopy & BAL in small animal
- inhaled form available
- metabolism is the same as salbutamol
Doxapram
- CNS stimulant: drug-induced resp depression, direct stim of medullary resp centres, stims resp in neonates - controversial
- fast onset –> emergency drug
- increases minute-ventilation
- not appropriate for assessment of laryngeal fxn
Neuromuscular blocking agents include…
Succinylcholine/Suxamethonium
Non-depolarizing agents
Aminosteroids: Vecuronium, Rocuronium, Pancuronium
Benzylisoquinolines: Atracurium, Cis-atracurium, Mivacurium
Indications for NMB
- ocular sx
- deep abd/thx cavity sx
- arrest ventilation
- limb relaxation
- when immobility is paramount
- reduce reflexes
- ease induction & intubation, avoid C, reduce laryngeal reflexes
- ventilation in ICU
Prior to NMB you must provide…
- appropriate hypnosis
- intubation & mechanical ventilation
- means to monitor the effectiveness of the block
- appropriate analgesia
Succinylcholine
- depolarizing agent (non-competitive)
- agonist at the Ach receptor –> causes AP & muscle contraction prior to relaxation
- Main use: faciltate intubation in cats (rare)
- Duration of action: 3 min
- recovery: 10-12 mins
Side effects of Succinylcholine
- Bradycardia (muscarinic stimulation in the sinoatrial node)
- Increase in K+ concentration
- If hyperkaliaemic, can be a concern
- Increase IOP
- Malignant hyperthermia (MH) – genetic condition, requires triggers
- Increased intragastric pressure
- Hypersensitivity (type I anaphylaxis)
- Muscle pain?
Succinylcholine contraindications
- eye injuries
- myopathies
- GDV
- Birds
- burn patients
- patients predisposed to MH
What are non-depolarizing agents?
- competitive mechanism w/ Ach, no AP
- req’s at least 90% of receptors blocked
- does not cross BBB
- metabolised in liver or excreted unchangd in urine
Atracurium undergoes what kind of elimination?
Hoffman elimination –> spontaneous degradation on pH & temp
req’s protection from light, keep in fridge
Atracurium
- Onset: 3-5 min
- Duration: 40 mins
- Possible histamine release (give slow, avoid in asthmatics)
- Hoffman degradation & non-specific esterases (Laudanosine –> seizures)
- suitable for renal/hepatic dz
- store in fridge
Cis-atracurium
- isomer of atracurium, 4x more potent
- Hoffman degradation
- No direct CV effects: no histamine release, less laudanosine produced
Mivacurium
- Onset: 2 mins
- Duration: 15 mins
- Histamine release
- Inactivated by plasma esterases –> long effects in dogs
- can be reversed w/ neostigmine/edrophonium
- offers no advantages over atracurium
Vecuronium
- Onset & duration similar to atracurium
- No direct CVS efffects
- Hepatic metabolism
- renal & biliary excretion
- Caution in liver/kidney patients
Rocuronium
- Fast onset, least potent
- short/intermediate duration
- high doses –> vagolytic
- anaphylactoid rxns reported
Reversal of NMB can be done by…
- spontaneous recovery (depolarizing agents)
- Achesterases can reverse non-depolarizing
What is the use of anticholinesterases?
- induce accumulation of Ach in post-ganglionic muscarinic receptors
- leads to: Bradyarrhythmia/asystole, hypotension, bronchoconstriction, increases Resp tract mucus secretion, hyperperistalsis (defecation), urination
Anticholinesterases should be given…
- slow IV injection over several minutes
- Should combine w/ atropine/glycopyrrolate
Edrophonium
- quarternary ammonium compound
- anticholinesterase that binds to enzyme at anionic site
- short-acting
- fast onset –> combine w/ atropine
- liver metabolism
- less muscarinic effects than neostigmine in horses
* used to Dx myasthenia gravis
Neostigmine
- quartenary ammonium compound
- anticholinesterase that binds to enzyme
- longer-acting than edrophonium
- slower onset –> combine w/ glycopyrrolate
- liver metabolism
Sugammadex
- initially for reversal of rocuronium
- fast-acting
- only for aminosteroids
- ineffective against benzylisoquinoline NMBA’s
- modified gamma-cyclodextrin
- chelates NMBA molecule
- no muscarinic effect
