Neuropharmacology Flashcards
How would you treat glaucoma?
Decrease production of aqueous humour - blockers of carbonic anhydrase –> acetazolamide, dorzolamide
Decrease blood flow to ciliary body - beta 2 agonists (timolol) or alpha 2 agonists (apraclonidine)
Increase clearance of aqueous humour
Open uveoscleral outflow with prostaglandin F2 analogues (e.g. Latanoprost)
Increase irido-corneal angle using muscarinic agonist (pilocarpine, anticholinesterase, physiostigmine) - ciliary muscle contraction
What drugs would you use to dilate the pupil?
Atropine
Cyclopentolate
Tropicamide
Phenylephrine
Stages of anaesthesia
Induction - voluntary and involuntary excitement
Maintenance - surgical anaesthesia
Recovery - or death
What is balanced anaesthesia?
Controlled reversible loss of consciousness with reduced perception of external stimuli and motor response.
3 basic points of balanced anaesthesia?
Sleep
Analgesia
Relaxation
Types of drugs used during anaesthetic?
Sedatives/hypnotics/tranquillisers Analgesics Induction agent (IV) Volatile anaesthetics Oxygen
Anaesthetics administered by inhalation
Di-ethyl ether (not used generally)
Nitrous oxide
The ‘anes’ halothane, isofluorane etc.
Anaesthetics administered by injection
Barbiturates (e.g. Pentobarbitone)
Propofol
Ketamine
Alphaxolone
Routes of administering anaesthetic (fast - slow)
Intravenous
Intraperitoneal
Intramuscular
Subcutaneous
Pros of injectable anaesthetics
Stage 1 and 2 passed rapidly Minimal equipment required Cheap (BUT Poor quality Little control)
Details of chloralose
1-2hrs long acting (alpha-chloralose = 8-10hrs) Light anaesthetic No analgesia Carcinogenic Used in rodents Few cardiopulmonary effects
Of pentobarbitone and phenobarbitone which is short and which is long acting?
Pentobarbitone - short acting - euthanasia
Phenobarbitone - long acting - epilepsy
What happens if you add alkyl groups to barbituric acid?
CNS depressive activity
Main barbiturates
Barbituric acid
Pentobarbitone (euthanal)
Phenobarbitone
Thiopentone (intraval)
Characteristics of thiopentone
Very lipid soluble Fast onset Induction agent Not much analgesia Respiratory depressant
Characteristics of propofol?
Lipophilic GABA channel opener
Safer than thipentone
Huge cvs depression
Not analgesic
Subtypes of GABA receptors ratio
2 alpha : 2 beta : 1 gamma
What are neurosteroids and their properties?
Neuroactive steroids Alphaxalone (alfaxan) Induction and maintenance Not as cumulative like thiopentone Less cvs than propofol (similar to thio)
Characteristics of ketamine
Dissociative anaesthetic
Hallucinogenic (Related to phencyclidine)
Antagonised (non-competitively) glutamate at NMDA receptors
Profound analgesia
Increases salivation and muscle tone
Superficial sleep (eyes open)
Used with alpha 2 agonists (xylazine)
List of inhalation agents
Isofluorane Halofluorane Sevofluorane Desfluorane Nitrous oxide Diethyl ether
Factors affecting the depth of anaesthesia
Concentration/partial pressure in brain
Potency of drug
Which gases have high partial pressures more quickly?
Very water INSOLUBLE gases
(If it’s soluble it stays In blood and doesn’t hit neurones)
Easy in, easy out
Which inhalation agents are least blood soluble?
Nitrous oxide
Servofluorane
Isofluorane
(Least to most)
What properties do you want to anaesthetise an animal quickly?
High concentration
Low solubility
What is the Meyer-Overton rule?
The more potent it is, the more readily it dissolves in oil
List drugs with decreasing potency
Halofluorane Isofluorane Servofluorane Ether Nitrous oxide
Characteristics of halothane
Low solubility
High potency
Sensitises heart to catecholamines
Depresses myocardium
Poor relaxation
20% metabolised with possible hepatotoxicity
Teratogenic - interferes with embryonic development
Characteristics of isofluorane
Similar to halothane Less blood soluble Vasodilator 100% excretion by lungs Lady-safe
Servofluorane
Turbo charged nitrous
V.low blood solubility
Little effect on heart
Characteristics of Nitrous oxide
Low potency
Good analgesic
2nd gas effect
Diffusion hypoxia
What is the second gas effect?
Rapid movement of nitrous oxide from alveolar space to blood leads to higher concentrations of other gases.
This is good
What is diffusion hypoxia?
Rapid movement of nitrous oxide from the blood to alveolar space driving out some of the oxygen
Types of sedatives
Benzodiazepines Chloral hydrate Alpha-agonists Phenothiazines Butyropherones
What does a sedative do?
Calm and drowsy
Sleep
What are sedatives used for?
Pre-med anaesthesia
Diagnostic procedures
Minor surgical procedures
Restraint (transport)
What does a tranquilliser do?
Calm and alert
Catalepsy
What are tranquillisers used for?
Calm nervy patients
Pre-med (anaesthesia)
Restraint
Neuroleptic - antipsychotic
Examples of minor and major tranquilizers
Minor - Diezepam
Major - ACP (acepromazine)
What do sedatives do?
Stop excitatory synapses or facilitate inhibitory synapses
What are benzodiazepines like?
Minor tranquilizers Sedation Muscle relaxation GABA antagonist Diezepam (Valium) -premed/postop
What is midazolam?
Similar to Diezepam
Shorter acting, potent
What does oxazepam do?
Appetite stimulation
What do alpha 2 agonists do?
Block Nad/neurotransmitter
Calming effect
Drowsiness, leghargy/sleep
Visceral (deep pain) analgesia
What effects do alpha 2 agonists have?
Muscle relaxation - glycine potentiating in spinal cord
Reduction in subsequent anaesthetic dose
Cvs depression
Examples of alpha 2 agonists
Xylazine - shorter (Rompun)
Detomidine - longer (Domosedan)
Medetomidine - better (Dormitor)
How would you use medetomidine?
Selective agonist, potent, deep sedation
Combine with injectable ketamine
Racemix - sedation, relaxation (dexmedetamine active d-isomer)
Ketamine (NDMA antagonist) analgesia or combo with opoid
What is an alpha 2 antagonist reversing agent?
Atipamezole - “antisedan” = used for waking up
What are Phenothiazines?
Major tranquilizers
Neuroleptics
Antagonist action
Example of phenothiazine
ACP - Acepromazine
Sedative or premed
(Combined with ket)
Effects other narcotics (reduce dose)
Side effects of chlorpromazine
Tremors In coordination Hypotension Hypothermia Male effects
What are butyrophenones?
Major tranquilizers Neuroleptic V potent Anti-emetic Neuroleptanalgesics Antipsychotic in humans Opioid in large game
What is an anti-emetic?
Helps motion sickness
Via D2/H antagonism in pathway from vestibular apparatus to chemoreceptors trigger zone in 4th ventricle
4 types of analgesia
NSAIDs
Corticosteroids
Local anaesthetics
Opioids
NSAIDs
Aspirin
Carprofen
Meloxicam
What are COX-1 and COX-2 responsible for?
COX-1 - housekeeping
COX-2 - inflammation and pain
What are coxibs?
Cox-2 inhibitor
Deracoxib
Firocoxib
Related to cox-2 selective inhibitors with coxibs name
What are cox-1 sparing inhibitors?
Carprofen
Meloxicam
Selective for cox-2 not 1
They aren’t coxibs
What are cox inhibitors
Aspirin
Ibuprofen
Cox-1 actions include platelet aggregation and mucosal protection
Inhibits this
What do corticosteroids do?
Inhibition of cox-1 and 2 sometimes decreasing expression of cox-2
Examples of local anaesthetics
Procaine
Lidocaine
Bupivacaine
- no post synaptic AP
What are opioid analgesics used for?
Peri-operative pain Sedation premed Neuroleptanalgesia - sedation with analgesia Restraint Anti-diarrhoea - codeine Anti-tussive
Opioid receptors
Dor (OPRD1) - hallucinations
Mor ( - supraspinal analgesia, respiratory depression, euphoria, physical dependence
Kor - spinal analgesia, sedation
Agonist at mor?
Morphine, pethidine, fentanyl
Agonist at mor and kor
Alfentanil
Remifentanil
Etorphine
Agonist at kor, antagonist at mor
Pentazocine
Buprenophine
Butorphanol
Antagonist at mor and kor
Naloxone (Narcan)
What does morphine do?
Cortex - sedation
Medulla - stimulation, depression
Peripheral GIT action (increased segmental tone, decreased peristalsis, increased sphincter tone, decreased secretions)
Also affects metabolism - liver, bile secretion
What is neuroleptanalgesia?
Neuroleptic and opioid
Profound analgesia
ACP and opioids
Methods of euthanasia (ways of disrupting CNS)?
Hypoxic disruption of CNS
Chemical disruption - 2ndary hypoxia
Electrical disruption - 2ndary hypoxia
Physical disruption/destruction of CNS - respiratory and cardiac arrest
Actual methods of euthanasia used?
Exsanguination
Anaesthetic overdose
Electric stun then exsanguination
Free bullet/captive bolt stun and pithing
Mechanism of anaesthetic overdose
Chemical CNS depression Unconsciousness Respiratory arrest Hypoxaemia Hypoxic CNS depression Cardiac arrest (myocardial hypoxia & deepening CNS hypoxia) Cessation of circulation (CNS hypoxia worsens indirectly) Death
What are cardio toxic agents used for?
Causing early cardiac arrest during anaesthetic overdose
What inhalation and injection agents can be used for euthanasia
Inhalation - CO2, CO+CO2, N2+Ar
Injection - barbiturates
Somulose - horses, dogs, cats, cattle (inject over 10-15 seconds to minimise premature cardiac arrest)
What is Hypercapnic Encephalopathy?
Acute respiratory acidosis
Headache, confusion, spasms
How to euthanise reptiles
Sedate heavily (IM), overdose ketamine Small reptiles, inhalation agent
