Lecture 9-11 - CNS depressant Flashcards
1
Q
What are organotropic drugs?
A
drugs that work on body organs
2
Q
What are etiotropic drugs?
A
drugs that acts on parasites, microber, bacteria
tumor cells
3
Q
What are the criterias for neurotransmitters?
A
- must be present in the nerve terminals
- must be relaesed on nerve stimulation
- exogenous application of the substance must mimic nerve stimulation
- it should be synthesized and stored in neurons
- it is inactivated or eliminated quickly
4
Q
What are the main excitatory amino acids and their effect
A
glutamate and aspartate
effect: depolarization (increases transmission)
5
Q
What are the main inhibitory amino acids and their effect?
A
Glycine and GABA
Effect: hyperpolarization (stabilization of post synaptic membrane)
6
Q
What transmitter belongs to the choline esters and what is the function?
A
Acetylcholine
(hyper)- or depolarisation
7
Q
What neurotransmitters belong to the monoamines?
A
noradrenaline
adrenaline
dopamine
serotonin
8
Q
what is the effect of noradrenaline?
A
postsynaptic alpha and beta
mood
blood pressure
9
Q
what is the effect of adrenaline?
A
locomotor activity
body temperature
10
Q
what is the effect of dopamine?
A
behaviour, locomotor activity
11
Q
What is the effect of serotoning?
A
prolactin secretion decreases
vomiting
sleep
body temperature
12
Q
What neurotransmitters belongs to the group of neuopeptides?
A
encephalins
endorphines
substance-P
neurokinins
13
Q
What is the effect of neuropeptides?
A
analgesia
respiratory and circulatory depression
euphoria
dysphoria
14
Q
Where can acethylcholine be found?
A
widely distributed throughout the CNS
15
Q
What receptors does Ach bind to and what is the consequence?
A
M1 receptors
closes: K+- Ca2+-, Cl–ion channels
16
Q
What happens to the cells when Ach binds?
A
depending on the type it will either depolarize or hyperpolarize
17
Q
How is Ach inactivated?
A
hydrolysis
Ach-esterase
18
Q
Where can Norephinephrine be found?
A
uneven distributions of the CNS
19
Q
What receptors is norephinephrine binding to?
A
Receptor alpha (a1-Gq -, A2Gi)
Beta (Gs)
20
Q
What is the task of a2 receptors?
A
important in control of sleep and wakefulness, mood and emotional behaviour, temperature
21
Q
What dopamine receptors do we have?
A
D1
D5 (Gs)
D2
D3
D4 (Gi)
22
Q
Where can dopamin be found in largest concentrations?
A
basal ganglia and limbic system
23
Q
What effect does dopamine excert?
A
inhibitory effect
fine control of movement
disturbances of behaviour
hypothalamic-pituitary functions
24
Q
What effect is excerted by serotonin?
A
strong inhibitory effect
hyperpolarization by increasing K+ and Na+ conductance
25
What is the result of serotonin stimualtion?
inhibits pain pathways in the spinal cord
helps ccontrol of behaviroual mood
26
what is the proposed regulatory function of serotonin?
sleep and wakefulness
mood and emotion
temperature
appetite
neuroendrocrine control
27
what effect does serotonin have on other neurotransmitters?
inhibits the release
28
What histamine receptors do we have?
H1 (Gq)
H2 (Gs)
H3
H4 (Gi)
29
where can histamine mostly be found?
posterior hypothalamus
30
what actions are histamin involved with?
regulation of arousal
temperature
and
vascular dynamics
31
What is the effect of histamin on other neurotransmitters?
decreases
Ach
5-HT
NA release
32
Where can glutamate and aspartate be found?
uniquely high concentration in brain
33
Where is GABA found
widely distributed in the CNS
highest concentration in
- basal ganglia
- hippocampus
- cerebellum
- spinal cord
34
What GABA receptors do we have and what is the action?
GABA a and b
facilitate Cl- and K+ ion transport, respectively
35
What is the action of glycine?
inhibits transmission between spinal interneurons and motor neurons
action is restricted to the spinal cord
36
What are the major purposes of the applications of drugs acting on CNS?
* **Prevention of seizures**
* increase well-being
* alteration of behaviour
* improvement of animal-human interaction
* induction sleep
* induction anaesthesia
* induction arousal
37
What are analeptics?
CNS stimulants
convulsants and respiratory stimulants
38
How do we classify CNS stimulants based on their site of action?
cortical
medullar
spinal
39
give some examples of drugs acting cortical
xanthines - coffein
cocain
amphetamines
psychotomimetics - LSD
40
give some exmaples of drugs that act medullar
xanthines- coffein
pentetrazol
doxapram
picrotoxin
41
give example of a drug that acts spinal
strychine
- toxic substance, motory, sensory activity stimulator
42
Doxapram is an example of a...?
respiratory stimulant
- short acting
given IV to treat acute resp failure
43
strychnine is an example of...?
miscellaneous convulsant
it is the antagonis of glycine, increases reflex excitablity of SC
no clinical use
44
what is picrotoxin an example of?
miscellaneous convulsant
non competitive antagonist of GABA
clinical use as respiratory stimulant
45
Name some psychotomimetic drugs
LSD
MDMA
Mescaline
Psilocybin
Phencyclidine
amphetamine
cocaine
methylxanthines
46
What is the mode of action of LSD?
agonist at 5-HT receptors
47
what is the mode of action of MDMA?
releases 5-HT and blocks reuptake
48
What is an example of methylxanthines?
caffein
49
What are the four identifiable actions in vitro of caffein?
1. adenosine receptor blockade
2. phosphodiesterase inhibition
3. action at Ca++ channels to increase entry of Ca++ into cells
4. binding to GABA receptors at the benzodiazepine site
50
What is the task of phosphodiesterase?
responsible for the breakdown of cAMP
51
What is the primary action of caffein?
direct action of blocking adenosine receptors
52
What is the general effect of adenosine that caffein will block?
inhibit neural activity
so the caffein will increase neural activity
53
What will the caffeins antagonism of adenosine action on A2a receptor in the globus pallidus cause?
decreases release of GABA (inhibitory neurotransmitter)
54
What is the effect of benzodiazepine and what effect can caffein have on this?
benzodiazepines acts by enhancing the effect of GABA on GABAa receptors
caffein has an opposite effect by inhibiting GABA release
55
Why does caffein cause vasoconstriction?
adenosine A2 receptors are prominent in endothelial cells, resulting in vasodilation - caffein counteracts adenosine effecct
56
What is the effect of methylxanthines on the heart?
postive ionotropic and chronotropic effect
57
what is the relationship between methylxanthines and peptic ulcers?
methylxanthines stimulate peptic acid secretion
58
How are analeptics classified?
Central analeptics
periferal analeptics
mixed analeptics
59
What are some example of central analeptics?
methyxanthins
picrotoxin
60
What are some examples of periferal analeptics
* cropropramide:crotetamied =prethcamid
* mixture of agents
* clinically available
* lobelin
61
what are some mixed analeptics?
doxapram
nicetamid, CO2, campho
62
How are the convulsants and respiratory stimulating drugs, doxapram, picrotoxin and strychnine used?
Doxapram: short-acting respiratory stimulant, used in acute respiratory failure
Strychnine: convulsant poison, acts on spinal cord by blocking receptors for the inhibitory transmitter glycine
picrotoxin: acts as GABAa antagonis, blocks ion channels
63
What are some things to consider about CNS depressants?
the nature of their effects
the site of action
the selectivity of the effect
the mode of action
64
What are the different categories based upon the nature of the effect of the CNS depressants?
Tranquilliser sedatives
Hypnosedatives
Analgesics
General anaesthetics
Anticonvulsants
Central muscle relaxants
65
What are the three major tranquilliser?
1. phentothiazine derivatives
2. butyrophenones
3. (Rauwolfia alkaloids - reserpine)
66
What are the phentothiazine derivative drugs?
propiopromazine
acepromazine
chlorpromazine
prometazine
67
Butyrophenones drugs
Azaperone
| (haloperidol, droperidol, fluanisone)
68
What are the 4 groupings of hypnosedatives?
1. alpha2-agonist
2. benzodiazepines
3. propandiol-derivatives
4. other compounds
69
Name som drugs that are alpha2-agonists
xylazine
medetomidinie, dexmedetomidine
romifidine, detomidine, anxiolytics
70
name som drugs that belong to Benzodiazepines
diazepam
chloridiazepoxide
71
Name a drug that belong to propandiol-derivatives
meprobamate
72
nae some other compounds that are hypnosedatives
barbiturates - long acting
alcohols
aldehydes
Br- and Mg2+ salts
73
What are psychotherpeutic drugs
compounds that influence behaviour, mood and emotional reactions
74
what are some psychotherapeatic drug categories?
anxiolytic drugs, sedative-hypnotic drugs
antipsychotic drugs
antidepressant drugs
75
What is the receptoral effects of tranquillisers on dopaminergic receptors?
D2 antagonists --\> antipsychotic effect
antimetic effect
increase in prolactin
parkinson-syndrome
76
Phenothiazine derivatives are ?
tranquillisers
77
How does tranquillisers act on the a-adrenoceptor
antagonistic
hypo tension
sedation?
78
what is the effect of tranquillisers on the muscarinic receptor?
antagonistic
mainly side effects
79
What is the effect of tranquillisers on H1-receptors?
antagonistic
sedation, antiemetic effect
80
what is the effect of tranquillisers on 5HT-receptors
antagonistic
enhancement of several effects
81
what are the pharmacological effects of phentothiazine derivatives?
potentation - sedatives, hypnotics, analgesic
vegetative tone decreases with increased relative parasympathetic tone
circulation
central antiemetic effect
regulation of body temperature
82
What are the uses of phenothiazines?
calming, sedation
muscle relaxation
premediaction before general anaesthesia
83
What are the side effects-contraindication of phenothiazines?
hypotention --\> collapse, tissue irritation, allergy
horses: excitation, penile prolaps
pets: thrid eyelid prolaps
prolactin increases
FSH,LH decrease
ADH and oxytocin decreases
epilepsy, extrapyramidal symptoms
84
How is the dosage of tranquillisers?
IV
IM
Po
range: 0,5-5 mg/kg
85
How is chloropromozine as a tranquilliser?
* side effects- frequently
* paradox reaction in horses
* cycli ataxia reaction with excitation hypotension and tachycardia
* rarely in other animals
* tissue irritation
* allergy
86
how is propriopromazine as an tranquilliser?
reliable, less side effects
87
How is acepromazine as an tranquilliser?
more efficacious than chloropromazine
less side effects
good oral bioavailability
halothane hyperthermia
arrythmogenicity
88
What is prometazine as a tranquilliser?
less potent tranquillizer
increased antihistaminic
anti-5-HT effect
89
How are butirophenones as tranquillisers?
* more potent than phentothiazines - analgesic effect
* in the CNS
* dopamine inhibition
* NA inhibition
* anticholinergic effect
90
what are the side effect-contradiction of butrophenones?
transient salivation or panting
hypotension, respiratory stim.
boar penile prolaps
should be avoided in cold conditions
91
what are the most characterisitic effects of sedative-hypnotics?
sedative effect
anxyolytic effect
hypnotic effect - induce or maintain sleep
muscle relaxation
anticonvulsive
92
what are the alpha2-agonists
xylazine
detomidine
dex/medetomidine
romifidine
93
what are the pharmacological effects of alpha2-agonists?
postsynaptic
* a2 and a1
* vasoconstriction
* transient hypertension
presynaptic
* a2
* vasoconstriction
* bradycardia
* vagus bradycardia
* hypotension
94
Alpha2-agonists pharmacologocal effects
activation of postsynaptic receptorss
vasoconstriction
transient hypertension
activation of baroreceptor
vagyllymediated bradycardia
95
ALPHA2-AGONISTS PHARMACOLOGOCAL EFFECTS
activation of presynaptic a2-receptors inhibits the release of NA
suppressed vasomotor tone - hypotension
analgesia and sedation
reduced motoractivity - recumbency
vagal bradycardia
96
ALPHA2-AGONISTS PHARMACOLOGOCAL EFFECTS
further effects due to activation of a2-receptors
GI SM relaxation
mydriasis, introcular pressure decreases
salivation decreases
release of insulin, renin and ADH decreases
ACTH increases
97
What are the side effects of Alfa2-adrenoreceptors in the different animals?
98
Pharmacokinetics of Alfa2-agonists
99
What type of drug is xylazine?
sedative-analgesic drug with depressed motor activity
100
what are the side effects of xylazine?
* emesis and vomiting in cats and dog
* bradycardia, malignant arrhytmias
* sweating in horses
* ecbolicaction - used as a contradiction in late pregnancies
* tympani in ruminants
101
What is the dose in
horses
cattle
dogs
cats
Horses:
* 2-3mg IM
* 0,5-10, mg/kg IV
cattle
* 0,05-0,2 mg/kg IM
Dog
* 1-2mg/kg IM
Cat
* 3mg/kg IM
102
What type of drug is detomidine?
a Sedative-analgesic drug more potent than xylazine
103
For what animal is detomidine used?
equine
104
why is detomidine a good drug for horses?
it does not cause loss of consciousness, and the duration of action is dose dependent
the horse can remain standing
105
What are the side effects of detomidine?
hypertension
bradycardia
respiratory depression
diuresis
hypothermia
sweating
snoring
tremor
106
How is detomidine used?
alone or in combination with ketamine. thiopentone, opioid drugs
107
what is the dosage of detomidine?
10-80 microgram/kg IM or IV
40microgrm/kg PO
108
Why is medetomidine and dexmedetomidine used?
it has similar effects as xylazine but is more reliable and safer
109
what species are best for Dex/medetomidine?
cats and dogs
110
what is the duration of action on medetomidine and dexmetomidine?
Medetomidine
* sedation: 1-3h
* analgesia: 5-15min
Dexmedetomidine
* sedation: 2h
* analgesia: 90 min
111
What is the dosage of dex/medetomidine?
Dogs: 10-80microg/kg IM -alone
10-20 microg/kg IV - combination
Cats: 50-150 microg/kg IM
112
What is the dosage of Romfidineromfidine
Horse and dog: 40-120 microg/kg IV, IM
Cat: 200-400 microgram/kg
113
What is the onset of remfidineromfidine?
IV: 2-4min
IM: 10-20
114
How long is the duration of romfidineromfidine?
sedation is a bit longer and causes less ataxia or recumbenxy than xylazine and detomidine
115
Some drugs that have the reverse effect of alpha2-agonists
alpha2-antagonists
atipamezole
tolazoline
yohimbine
116
What kind of drug is atipamezole, which specific drug does it reverse?
alpha2-adenoreceptor blocking agent
reverses the effect pf medetomidine
117
what are the side effects of atipamezole?
it is well tolerated in dogs and cats
tachycardia
transient hypotension
hypothermia
vomiting
defecation
panting
muscle tremor
118
what is the contraindication of atipamezole?
ketamine-medetomidine
119
What is the dose of atipamezole?
horse: 150 microgram/kg
dogs: 5 times
cats: 2,5 times the dose of medetomidine
120
What type of drugs are yohimbine and telazoline?
what drug does it have reverse effect of?
significant alpha1-antagonistic action
reverse effect of xylazine
121
Yohombine is mainly used in combinations with another drug, which drug is it and why?
Fampiridine
it facilitates the release of neurotransmitters from nerve endings
122
What is meant by receptoral action?
they facilitate or amplify the inhibitory activity of GABA
- possibly by eliciting a structural alteration in the GABA-receptor complex, resulting in an opening of chloride ion channels
123
Where are benzodiazepine receptors found?
located in all levels of CNS and in muscles
124
What si the effect of benzodiazepines?
sedation and anxiolytic effect
anticonvulsive effect
muscle relaxation
hypnotic
125
what is the antidote to benzodiazepine?
flumazenil and sarmazenil
in case of overdose of certain BDZs, dose 100 µg/ttkg IV (duration of action is to short in human)
40 µg/ttkg (horses) IV q24h, respectively
126
How is the pharmocokinetics of diazepam?
- absorption
- binding?
- excretion
oral absorption is good, IM is delayed
it binds significantly to plasma proteins
excretion: after demethylation and conjugation via the kidney
127
what is the clinical use of diazepam?
premediacation and combination (ketmaine)
muscle relaxation
prevention and control of epilepsy
sedation
128
What is the interaction and contraindication of diazepam?
* paradoxical reaction
* cat
* greyhound
* aminoglycosides
* inhibition of respiration
* before and during delivery
* enormous high doses
* liver diseases
* rare hepatotoxicity esp. cats
129
What is the dosage of diazepam?
sedation: 1-15 mg/kg PO
pre-medication: 0,2 mg/kg IV
status epilepticus: 5-10 mg/kg (dog??) IV then 2-5mg/hour IV
130
How is the function of midazolam and what is the dosage?
shorter effect, produces less sedation than diazepam
dosage: horses 0,05-0,2 mg/kg
dogs and cats: 0,1-0,5 mg/kg IV 0,3-1 IM
131
Name some anxiolytic drugs belonging to 1,4-benzodiazepines
* Chlordiazepoxid (Elenium, Librium) +
* Nitrazepam (Eunoctin) +
* Temazepam +
* DIAZEPAM (Seduxen, Valium) ++
* Oxazepam ++
* Medazepam (Rudotel) ++
* MIDAZOLAM (Dormicum) (+AC) \* +++
* ZOLAZEPAM (Zoletil) +++
* Alprazolam (Xanax) +++
* Lorazepam (+AC) +++
* Clorazepate (+AC) +++
* Clonazepam (+AC) ++
132
What is the mechanism of effects combined with baribiturates?
GABA-BDZ-barbiturates-receptor complex
further supposed effects: decrease in Ca2+ accumulation: inhibition in release of stimulatory transmitters stabilisation of membranes
general inhibition - but sensitivity of certain structures differs
133
what are the pharmacological effects of barbiturates?
CNS
circulation
respiration
134
what are the kinetics of barbiturates?
low pka - Na, K-salt
lipophylicity
lipoid/water partition
redistribution
metabolism
135
What is the classification of barbiturates according to the duration of action
long acting - barbital, phenobarbital
middle-long action - amobarbital, butobarbital
136
What is the dosage of barbiturates?
dose: dogs + cats PO i,5mg/kg B.I.D
tetanic horses: IV 12 mg/kg initial
6 mg/kg B.I.D to maintain
137
How is the comparison between hypno-sedatives and tranquillisers?
