Central Nervous System Pharmacology Flashcards
(151 cards)
1
Q
What is the difference between a sedative given at a low dose and high dose?
A
Low dose causes animal to be calm and drowsy
High dose causes sleep but not anaesthesia
2
Q
What does a low and high dose of a tranquilliser cause?
A
Low- calm but alert and responsive
High- Catalepsy (altered state of consciousness, not asleep)
3
Q
What does an anxiolytic cause?
A
Calm with altered response to stimuli
4
Q
What is a neuroleptic?
A
Specifically the effects of phenothiazines or butyrophenones in the CNS
5
Q
What is neuroleptanalgeisa?
A
Combination og neuroleptic and an opioid
6
Q
What are the 4 main classes of sedatives?
A
Alpha 2 agonists- most common
Phenothiazines
Butyrophenones
Benzodiazepines- least common
7
Q
What is the term for sedatives that effect post synaptic receptors and pre-synaptic receptors?
A
Post- Symptathomimesis
Pre- Sympatholysis
8
Q
What is the mechanism of action of alpha 2 agonists?
A
Endogenous neurotransmitter that binds to alpha 2 is noradrenaline
Exogenous a2 is designed to be variously selective fat a2 receptors
Most a2 receptors in periphery are post synaptic so peripheral effects mainly sympathomimetic- vasodilation
Most a2 receptors are pre synaptic so sympatholytic- sedation
9
Q
What is the mechanism of action of phenothiazines?
A
Only ace-romaine licensed
Antagonists
Antagonist at receptors alpha 1 adreno-receptors (vasodilation) , dopamine 2 receptors (sedation, muscle relaxation), histamine receptors (anti-emetic, reduces hypersensitivity), serotonin receptors (decreased alertness), muscarinic (reduced parasympathetic tone)
In order of most effected to least
10
Q
What is the mechanism of action of butyrophenones?
A
Similar to phenothiazines
Dopamine receptor 2 agonists- sedation and muscle relaxation
Histamine receptor antagonists- anti-emetic, reduces hypersensitivity
11
Q
What is the mode of action of benzodiazepines?
A
Endogenous neurotransmitter that binds to GABA receptors- an inhibitory neurotransmitter
Causes decreases resting membrane potential
12
Q
How are alpha 2 agonists administered?
A
Water soluble so can be injected intravenously and intramuscularly
Molecules are lipid soluble so can be subcutaneous or epidurally or orally
13
Q
How are phenothiazines administered?
A
Water soluble so IV and IM
Lipid soluble so SC, orally
Tablets least effective
14
Q
How are butyrophenones administered?
A
Intraperitoneal and IM
15
Q
How are benzodiazepines administered?
A
IM and IV
16
Q
What are examples of a2 agonists in order of increasing length?
A
Xylazine Detomidine Romfidine Medetoidine Dexmedetomidine
17
Q
What is an example of a Phenothiazines?
A
Acepromazine
18
Q
What is an example of a butyrophenones
A
Fluanisone
Azeperone
19
Q
What is an example of a benzodiazepines?
A
Diazepam and midazolam
20
Q
What are the effects and side effects of a2 agonists?
A
Beneficial- sedation, analgesia, muscle relaxant, ‘anaesthetic sparing’ agents
Side effects- deleterious CV effects- vasoconstriction increases after load, diuresis, hyperglycaemia, sweating
Antagonists available
21
Q
What are the effects and side effects of acepromazine (phenothiazines)?
A
Sedation but less predictable, muscle relaxation, anaesthetic sparing, anti-emetic, long lasting, no analgesia
Side effects- vasodilation, paraphimosis, brachycephalic/exited animals have adrenalin reversal, anti-histamine, long lasting
22
Q
What are the effects of butryophenones?
A
Sedation, muscle relaxation, anti-emetic, anti-histamine
Side effects- no analgesia, vasodilation
23
Q
What are the effects of benzodiazepines?
A
Sedation, muscle relaxation, minimal CV effects
No analgesia
Side effects- can cause excitement if administrated on their own
Antagonists available
24
Q
How can neurotransmitters alter the behaviour of animals?
A
Drugs are used to influence behaviour and emotional state- act by altering the efficacy levels of one or more neurotransmitters
25
What neurotransmitters can alter behaviour?
Serotonin- involved in regulation of mood, appetite, arousal, role in pain inhibition
Dopamine- major role in reward and pleasure, helps regulate emotional responses
GABA- main inhibitory neurotransmitter
Noradrenaline- helps form connections in the brain
26
What are the 5 main groups of psychoactive drugs?
```
Tricyclic antidepressants
Specific serotonin reuptake inhibitors
Monoamine oxidase inhibitors
Benzodiazepines
Beta-blockers
```
27
What is the action of TCAs (tricyclic anti-depressants)?
Block the serotonins and noradrenaline transporters inhibiting reuptake, increases serotonin in synapses for longer
28
What are TCAs used to treat, what are the potential side effects?
Mainly used in anxiety disorders
Prolonged use down regulated 5-HT and NA receptors
Significant antihistamine, anticholinergic and alpha-1 agonist effect
Affects Na/Ca channels so should be avoided
29
What is the MOA of SSRIs (specific serotonin reuptake inhibitors), what problem occurs from overuse?
Inhibit uptake of serotonin
Overuse down regulates post-synaptic serotonin receptors
Less side effects then TCAs
30
What is the MOA of MAOIs (monoamine oxidase inhibitors)?
Monoamine oxidase is an enzyme found in many tissues including CNS
MAO A/B are involved in breakdown or serotonin, noradrenaline and dopamine
Only MAO B used in vet
31
What are beta-blockers used for and what do they cause?
Used in anxiety/anticipation scenarios
Reduce physiological signs of negative emotion states involving panic and stress
Central effect inhibits consolidation of memory
32
What are AEDs? (anti-epileptic drugs)
Can have applications in behavioural modification
33
Name 3 examples of TCAs?
Amitriptyline
Doxepin
Clomipramine- licensed in dogs
34
What is an example of an SSRI?
Fluoxetine- not authorised in UK
35
Name an example of a MAOI?
Selegiline is a MAO-B inhibitor for CCDS
36
Name an example of BZDs?
Alprazolam- non-licensed used in dogs
37
What is an example of a beta blocker?
Propanolol
38
Name 2 examples of AEDs?
Topiramate
| Imeptoin
39
Describe the pharmacokinetics of TCAs?
Extensive first pass metabolism, highly protein boind, hepatically metabolised, bile excretion
40
Describe the pharmacokinetics of Fluoxetine?
First pass hepatic metabolism after oral admin, highly protein bound, hepatic metabolism, urine excretion
41
Describe the pharmacokinetics of selegiline?
Elimination half life 1 hour, hepatically metabolises to methylamphetamine
42
What can be used instead of drugs?
Pheromones- adaptil, feliway
43
What are the major classes of analgesic drugs?
```
No plant
NSAIDs
Opioids
Paracetamol
Local anaesthetics
Alpha 2 agonists
NMDA antagonists
Tramadol
```
44
What is the mechanism of action of NSAIDs?
Inhibit COX1- physiological and COX2 inducible (inflammatory)
45
What is the mechanism of action of opioids?
Receptors throughout the body, main analgesic effect is via the dorsal horn of the spinal cord, reduce exitatory neurotransmitter at nerve endings
46
What are the different types of receptors opioids effects?
Mu- analgesia
Kappa- sedation, some analgesia
Delta
47
What is the mechanism of action of paracetamol?
Precise mechanism not known- COX 1 inhibitor
48
What is the action of local anaesthetics?
Amides and esters- amides last longer
| enter centres of axons and block sodium channels
49
How are each of the analgesics administered NO PLANT?
NSAIDs- IV, IM, SC, PO, Topical
Opioids- IV, IM, SC, PO, Topical, Transmucosal, Extradural, Synovial
Local anaesthetics- IV, Topical, Local infiltration, Transmucosal, Extradural, Perineurally, Synovial
NMDA- ketamine- IV, SC, IM, Transmucosal, Epidurla
50
What is the action of NMDA antogonists?
NMDA receptors involved in pain pathway in the CNS
51
What are the effects and side effects of NSAIDs?
Analgesia, Anti-inflammatory, Anti-pyrexia
| Side effects- GI, renal (auto regulation of blood flow), Clotting, Liver, gastric ulceration
52
What are the effects and side effects of opioids?
Analgesia, sedation
| Side effects- Bradycardia, respiratory 'depression', reduces GI motility, Excitement, Dysphoria, Vomiting
53
What are the effects and side effects of paracetamol?
Analgesia, anti-pyrexia
| Side effects- Hepatotoxicity, Hypotension, No cats
54
What are the effects of local anaesthetics and the side effects?
Analgesia, Anti-inflammatory, anti-arrhythmic
| Side effects- loss of effects of nerves, CNS toxicity, Myocardial toxicity
55
What are the effects and side effects of NMDA antagonists?
NMDA antagonists- Analgesia, ketamine- anaesthesia
| Side effects- Excitement, Hypertonicity, myocardial depression, sympathetic stimulation
56
What drugs are used for chronic pain?
Gabapentin, amantadine, antidepressants
57
Name some examples of opioids that cause full Mu, Partial Mu, Mu antagonists/Kappa antagonists
What what is their antagonist?
Full Mu- Morphine, methadone, pethidine, fentanyl
Partial Mu- buprenorphine.
Mu antagonists/Kappa agonists- butorphanol.
Antagonists- Naloxone
58
What is an example of a local anaesthetics?
Lidocaine
59
List the injectable anaesthetic agents used in UK vets
Propofol
Alfaxalone
Thiopental
Etomidate
60
List the inhalation anaesthetics used in UK vets
```
Isoflurane
Sevoflurane
Halothane
Desflurane
Nitrous oxide
```
61
What are the advantages and disadvantages of injectable anaesthetic agents?
Simple equipment to administer
Once administered they need to be metabolised and excreted to be removed
Adjustment of doses to effect may be harder that inhalation agents
62
What are the advantages and disadvantages of inhalation anaesthetic agents?
```
Specialised equipment required
Easy to eliminate
Easy to adjust depth
Delivered in oxygen
Potential for environment contamination
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63
What is the MOA, administration and effects of propofol?
Gaba agonists
IV only- emulsion
Recovery due to distribution and hepatic metabolism
Effects- anaesthesia, sedation (low dose), muscle relaxation, anti-seizure
Side effects- Vasodilation, respiratory depression
64
What is the MOA, administration and effects of alfaxalone?
GABA agonist
Neurosteroid with poor solubility, made water soluble IV, IM, SC
Recovery due to redistribution, hepatic metabolism
Effects- anaesthesia, sedation (low dose), muscle relaxation, anti-seizure
Side effects- vasodilation, respiration depression, excitable recovery
65
What is the MOA, administration and effects of Ketamine?
NMDA agonist
IV, IM, SC, Transmucosal
Recovery due to redistribution/metabolism (excretion in cats)
Effects- anaesthetics, analgesia
Side effects- direct myocardial depression, increased HR, vasoconstriction, respiratory depression
66
What is the MOA, administration and effects of Thiopental?
GABA agonists
IV
Redistribution recovery, slow hepatic metabolism
Effects- anaesthesia, muscle relaxation, anti-seizure activity
Side effects- myocardial depression, arrythmogenic, respiratory depression irritant extravascularly
67
What is the mechanism of action of inhalation anaesthetic agents?
Not completely understood
68
What is the MAC of an inhalation anaesthetic?
Minimum alveolar concentration- of an agent at which 50% of patients will not respond a % of atm
69
What MAC is used for surgery?
1.2-1.5x MAC
70
Side effects more pronounced around what MAC?
2.5x MAC
71
What affects MAC?
Species, age, Low O2, other agents on CNS, catecholamines, pregnancy, low blood pressure, body temp
72
What are the effects of sevoflurane and isoflurane, which is cheaper and more potent?
Effects- respiratory depression and potent vasodilation, anaesthetic
Isoflurane more potent and cheaper
73
What is the triad of anaesthesia?
Muscle relaxation, unconsciousness, analgesia
74
What is a seizure?
A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain
75
What are the 4 clinical components/phases of a seizure?
Prodromal, aura, lctus, post-ictal
76
What happens during prodromal phase?
Before the seizure begins, behavioural changes occur such as wining or hiding- hours to days before
77
What happens during aura phase?
First part of seizure, hours to minutes before, odd behaviour such as barking, pacing, salivating
78
What happens during Ictus?
Proper seizure, involuntary muscle movement, twitches and changes in tone
79
What happens during post-octal phase?
Period of time where the animal is disorientated, change in appetite, thirst, toileting
80
What is classes as a an isolates seizure, a cluster of seizures and a status epilepticcus?
Isolates- 1 in 24 hours
Cluster- 2 or more in 24 hours
Status epilepticcus- last over 5 mins or repeated seizures
81
Where do seizures occur in the brain?
Located in the forebrain
82
What is the difference between a foal seizure and general?
Focal involves a specific site (cerebellum)
| Generalised (both hemispheres)
83
What are focal seizures associated with?
Focal disease process in the brain
84
Which are the more commonly recognised seizure?
Generalised- classic tonic-clonic type- loss of consciousness, bilateral convulsions
85
What can cause seizures?
Disease in brain
| Disease outside brain- metabolic/toxic, still originates from the brain
86
Why do seizures occur?
An imbalance of excitation and inhibition of neurotransmission in the brain
Can occur from excessive synchronous depolarisation of enough neurones in the brain will lead to a seizure (excessive excitation or insufficient inhibition)
87
What forms an epileptic focus of pacemaker cells?
Groups of cells possessing an intrinsically high spontaneous firing activity
88
Why do seizures need to be treated?
It causes damage to the brain and leads to increased pacemaker cells increasing seizure activity
Cluster seizure raises blood pressure and body temp rises to dangerous levels
89
Successful treatment reduces seizures by what?
50%
90
What three broad categories are used for treat seizures?
Enhance GABA, Suppress Glutamate, Modulate movement of cations
91
How are anti-epileptic drugs split?
First line and add on for further therapy
92
Name the first line AEDs?
Phenobarbital
Potassium Bromide
Imepitoin
Diazepam
93
Name the add on AEDs?
```
Gabapentin
Pregabalin
Levetiracetam
Zonisamide
Topiramate
Felbamate
```
94
What is the MOA of phenobarbital, administration, half life and pharmacokinetics?
MOA- enhancing GABA-induces chloride ion conductance (hyperpolarising neuronal membranes)
Admin- Orally, IV
Half life- 24-40 hours takes 10-14 days for steady state
Phar- 50% is protein bound so don't use with other highly protein bound drugs. Hepatically metabolised
95
What is the MOA of potassium bromide, administration, half life, excretion?
MOA- enhances GABA induced Cl- conductance
Administration- oral but mucosal irritant
Half life- 25-46 days, 3 months to steady
Renal excreted- competes with Cl- ions
Not cats
96
What is the MOA of Imepitoin, administration, half life?
Partial agonists at the benzodiazepine site of GABAa receptor- potentiates action of GABA
Oral administration- better on empty stomach
Half life- 1.5-2 hours, 3 days to reach steady
97
What is imepitoin not recommended for and what can it be used with?
Not recommended for cluster seizures
| Single agent of add on to phenobarbitone
98
What is the MOA of diazepam, when is it mainly used for treatment of seizures, admin, what does it cause significant side effects in?
MOA- Benzodiazipine receptors activate the GABA chloride channel similar to phenobarbital
Appropriate sue in emergency treatment of seizures
Admin- IV or rectum
50% of cats have significant side effects
99
What is the MOA of gabapentin, how is it excreted?
MOA- enhances GABA action, reduces glutamate activity, inactivate Na channels and reduce action of Ca channels
Renal excreted
100
What is the MOA of Pregabalin, how is it excreted?
Structural analogue of GABA similar MOA to gabapentin
| Renally excretes- minimal protein bound
101
What is the MOA of levetiracetam, how is it excreted?
Main MOA decreases glutamate release- also enhances GABA mediated Cl- conductance
Rapidly metabolised
Renal excretion
102
What is the MOA of Zonisamide and what are its pharmacokinetics?
Affects ion channels- reduction of flow through Ca channels
Long half-life
Hight protein bound
Hepatically metabolised
103
What is the MOA of topiramate, how is it excreted?
Potentiales GABA activity
| Renal excretion
104
What is the MOA of felbamate and its pharmacokinetics?
Increases seizure threshold by reducing glutamate mediated exitation
High bioavailability
High protein bound
Metabolised by hepatic microsomal enzymes
105
How can drugs be administered to the eye?
Topical can penetrate the globe, by crossing the cornea, conjunctiva or sclera or systemically by crossing blood:ocular barrier
106
What are the advantages to topical administration of the eye?
Convenient
Easy and specific
Minimal side effects
107
What are the tree ways topical eye drugs are distributed?
Drained by lacrimal drainage system, penetrates into eye cornea/sclera, enters systemic circulation through conjunctival and nasal mucosal vessels
108
Why are drugs quickly removed from the surface of the eye?
Constant production, distribution and drainage of the pre-ocular film means drugs are removed rapidly
109
Why do topical eye drugs need to have a certain osmolarity and pH?
If agents were irritant they would induce lacrimation and blinking
110
Why do several drops of drugs to the eye need to be administered 10 mins apart?
Second drop will displace first reducing efficacy of both
111
How can intraoccular bioavailability be improved?
Increasing the retention of the drug in the palpebral fissure or increasing its ability to penetrate the cornea
112
How are ocular drugs supplied?
Supplied as ointments which contain an oily base, agent is either suspended/dissolved in base- reducing frequency of application
113
Why has the agents used for eyes increased viscosity?
To increase retention, but beyond a certain viscosity would be irritant
114
How can agents now use bioadhesion to increase retention?
Form a gel by binding to the mucin layer of the tear film
115
How can topical drugs enter the eye?
Penetrate the cornea
| Absorption through conjunctiva and sclera
116
What is the first barrier to topical drugs entering the eye and what influences how easily drugs pass through?
Corneal epithelium
| Lipid solubility
117
How do most topical drugs enter the eye?
Through the cornea
118
What is the second barrier of cornea to topical drugs and what influences what passes through?
Stroma- has high water content so facilitates diffusion of water soluble drugs, barrier to lipid soluble
119
Why can both lipid and water soluble pass through the endothelium begin the stroma?
Is one cell thick and has gap junctions
120
What do topical drugs that enter the eye therefore require in terms of properties?
Both hydrophilic and lipophilic characteristics
121
What affects water solubility and lipid solubility of drugs entering the cornea?
Degree of ionisation
122
How do most ophthalmic drugs exist in solution?
Weak acid/bases that exist in a balances solution of ionised and unionised forms
123
Which is water soluble/ lipid soluble from ionised and un-ionised?
Water soluble- ionised
| Lipid soluble- un-ionised
124
How is a balanced solution of ionised and non-ionised form of a drug best for corneal penetration?
The un-ionised form crosses the corneal epithelium more easily. Once in the stroma the unionised drug ionises because of its abundance and more easily passes through the water high stroma. As it reaches the endothelium the ionised fraction is in abundance therefore more becomes un-ionised to cross the endothelium
125
What affects the balance of ionised: unionised and how can this be disrupted?
The pH
| Small variations in pH such as with infection can massively effect absorption
126
What clinical factors affect corneal penetration?
Drugs can bind to protein in tear film- in inflammation increased protein in tear film
Damaged cornea- corneal ulceration will have increased corneal penetration of water-soluble drugs
127
How can drugs be absorbed non-corneally?
Large hydrophilic molecules can still enter the eyeball, by absorbing across the conjunctiva and sclera
From conjunctiva the drugs can penetrate the eye via the sclera and enter the posterior segment or scleral vessels to the ciliary body
128
How do topical agents systemically become absorbed into the eye?
Highly vascular tissue such as conjunctiva and the mucosa and nasopharynx enable absorption into blood stream
129
How are eye topical drugs distributed and metabolised?
After cornea it moves into aqueous humour and to the iris and ciliary body
Lens and vitreous humour receive lower levels of corneally absorbed drugs
Drugs from non-corneal go to iris and ciliary body though blood supply
130
How are drugs systemically administered to the eye?
Pass through the blood : ocular barrier which consists of the blood : aqueous barrier and blood : retinal barrier
Hydrophilic penetrate poorly, lipophilic readily, unless compromise
131
Why is pupil dilation needed?
For better fundic examination
132
What drugs cause dilation of the pupil?
parasympatholytics - relax the iris
| Sympathomimetics- contract the dilator muscle
133
What else can dilation drugs be used for?
To cause relaxation of the muscle in the ciliary body to relieve painful spasms in cases of anterior uveitis
134
What are three examples of pupil dilators?
Atropine
Tropicamide
Phenylephrine
135
What is the action, onset and length of action of Atropine?
MOA- parasympatholytic
Bitter tasting cause salivation
1 hour onset 120 hours acting
136
How long does it take tropic amide to onset and last?
30 mins onset
| Acts for 8-12 hours
137
How long does it take phenylephrine to act and what type of drug is it?
10 mins of application
| Selective alpha adrenergic drug
138
What drugs actively increase tear production?
Parasympathomimetic- pilocarpine
| Immunosupressant- ciclosporin
139
What are the three categories of tear substitutes?
Aqueous, mucin, lipid
140
What is the problem with aqueous substitutes?
Quickly lost from the ocular surface
141
What is the most commonly used mucin later substitute?
Carbomer gel
142
What is glaucoma?
Sustained increase in intraocular pressure
143
What usually causes glaucoma?
Reduces aqueous humour flow
144
How can glaucoma therefore be treated?
Increase outflow or reduce production of aqueous humour flow or both
145
What are used as the first line of treatment of glaucomas and why?
Osmotic diuretics
Increase in blood tonicity causes water to be drawn out
Relies on intact blood:occular barrier
146
What other drugs can be used to treat glaucomas?
Carbonic anhydrase inhibitors
Prostaglandin analogues
Beta-blockers
Parasympathomimetics
147
How do carbonic anhydrase inhibitors treat glaucoma?
Catalyses the hydration of CO2 to bicarb and H+ in non-pigmented ciliary body of epithelium, bicarb moves into aqueous humour, water follows
Inhibition reduces production of aqueous humour
148
Name two examples of carbonic anhydrase inhibitors used for glaucomas?
Brinzolamide
| Dorzolamide
149
How do prostaglandin analogues treat glaucoma and name an example?
Increase uveoscleral outflow of aqueous humour due to alteration in ultrastructure of outflow tract
Latanoprost
150
How do beta blockers treat glaucoma and name an example?
Uncertain mechanisms
Betaxolol
151
How do parasympathomimetics treat glaucoma and what is used?
Cause constriction of ciliary body and constriction of pupil- widens the drainage angle incease in outflow if intact
Pilocarpine used
