9. Sedato-hypnotics Flashcards
(26 cards)
What are sedato-hypnotics?
They are used to reduce tension, anxiety and induce sedation or to induce sleep (hypnotic effect)
Often administered before surgical procedures or to ensure the animal remains calm for diagnostic purposes.
Drug groups of sedato-hypnotics
- Alpha 2 agonists
- Alpha 2 antagonists
- Barbiturates
- Benzodiazepines
Alpha 2 agonists, Active substances
- Xylazine
- Medetomidine
- Dexmedetomidine
- Romifidine
- Detomidine
Alpha 2 antagonists, Active substances
- Atipamezole
- Yohimbine
- Telazoline
Barbiturates, active substances
- Phenobarbital
- Pentobarbital
- Thiopental
- Methohexital
Benzodiazepines, active substances
- Diazepam
- Midazolam
- Zolazepam
- Alprazolam
- Lorazepam
Alpha 2 agonists, mechanism of action
Alpha-2 receptors are “switches” that are turned on by a drug (agonist), and this will cause specific effects.
The receptors are found both before and after nerve connections ⭢ Postsynaptic and presynaptic
1. Presynaptic activation
When the drug activates alpha-2 receptors before the nerve connections, it causes:
- Sedation and short-term analgesia
- Decreased motor activity and recumbency
- Increased blood sugar due to increased glucose production
- Relaxation of the digestive system, which can lead to bloating
2. Postsynaptic activation
When the drug activates alpha-2 receptors after the nerve connections, it also ends up activating the alpha-1 receptors. This causes:
- Vasoconstriction
- Temporary increased blood pressure (transient hypertension)
- Slowing the heart down (reflex bradycardia) and lowers the blood pressure as a triggering response
Alpha 2 agonists, pharmacokinetics
1. Absorption: Overall fast for every alpha-2 agonist
2. Distribution: Overall good for every alpha-1 agonist
3. Metabolism: Liver
4. Excretion: Through urine
5. Transport: By plasma proteins
The onset of sedative effect differs between the different drugs:
Xylazine = IV; few minutes, IM; 10-15 minutes
Detomidine = IV; Immediately, IM; few minutes
Medetomidine = IV; Immediately, IM; Few minutes
Alpha 2 agonists, side effects
- Hypotension
- Bradycardia
- Vasoconstriction
- Polyuria
- Emesis in cats and dogs
- Tympani in cattle
Alpha 2 agonists, indications
1. Xylazine = Sedative-analgesic drug with depressed motor activity. It can be used in all domestic animals, but it has low potency in swine.
The analgesic effect is short !!
2. Detomidine = More potent than xylazine, licensed only for equine use. Does NOT cause total loss of consciousness.
It is used either alone or in combination with for example, ketamine, opioids.
3. Medetomidine/Dexmedetomidine = Similar to xylazine, but seems more reliable and safer. Developed for cats and dogs
Alpha 2 agonists, pharmacological effect
- Sedation
- Analgesic effect
- Reduced motor activity
- Relaxation of GI smoot muscle
- Mydriasis
- Decreased intraarticular pressure
Alpha 2 agonists, antidote
Usage of alpha-2 antagonists
Alpha-2 antagonists, mechanism of action
1. Atipamezole
It is very specific and mainly blocks the alpha-2 receptors, reversing the effects of alpha-2 agonists, such as medetomidine.
2. Yohimbine & Telazoline
Are much less specific, and therefore also has significant alpha-1 antagonistic action, reversing the drugs like xylazine
Alpha-2 antagonists, side effects
Well tolerated by dogs and cat
- Tachycardia with high doses
- Transient hypotension ⭢ temporary low blood pressure
- Vomiting
- Panting
- Muscle tremors
Alpha-2 antagonists, contraindications
Do not use the combination of ketamin-medetomidine in horses and dogs, due to the potential for problematic cardiovascular effects: arrythmias, myocardial oxygen imbalance. The overall effect is very unpredictable and the side effects are serious.
Barbiturates, chemical strucuture
Structure-based barbituric acid
Barbiturates, mechanism of action
The barbiturates work by enhancing the effects of a calming chemical in the brain, called GABA. This will reduce the calcium buildup in the nerve cells (neurons), which then decreases the release of stimulating effect.
The overall effect is to calm down the central nervous system, but not all parts of the brain are affected equally. This uneven effect is why some of these drugs can be used as a general anaesthetic
Barbiturates, pharmacological effect
- Sedative
- Hypnotic and mild anxiolytic effect (=reducing anexiety and fear in animals)
- Significant anticonvulsant effect
Barbiturates, pharmacokinetics
- Low pKa
How easily barbiturates become charged / uncharged molecules. Important because they get absorbed differently
- Lipophilicity
Barbiturates need to cross the cell membrane to reach the target cells. The membranes are fatty, so a barbiturate that dissolves well in fat (lipophilic) can cross the membranes more easily.
- Redistribution
The more blood supply ⭢ The more drug. BUT, other tissues like fat can absorb the drug, so the brain can redistribute the drug (The brain gets a lot of drug because higher blood supply.
- Metabolism
Mainly in the liver
- Strong activation of CYP450
CYP450 are primarily responsible for the metabolism, strong activation can lead to: increased drug metabolism, high tolerance
Barbiturates, side effects
- Ataxias
- Oversedation
- Liver toxicity
- Polyuria, polydipsia
- Obesity
Benzodiazepines, mechanism of action
Benzodiazepines affect the GABA receptors. Normally, the GABA receptors are a neurotransmitter that inhibits the activity of nerve cells in the central nervous system.
Benzodiazepines facilitate or amplify the GABA’s inhibitory effect, which is done by potentially causing a structural change in the GABA receptor complex.
This structural change leads to the opening of chloride ion channels.
The benzodiazepines bind to BZD receptors (Benzodiazepine receptors), which are found throughout the CNS and in muscles.
This binding opens the GABA-gated chloride channels, leading to hyperpolarisation, which makes it harder for a nerve cell to fire, resulting in CNS and muscle depression
Benzodiazepines, pharmacological effects
- Hypnotic
- Sedation and anxiolytic effect (=reducing anxiety and fear in animals)
- Muscle relaxation
- In animals: primarily used as sedative, but also has a hypnotic effect with increasing dose.
- Sedation and pre-anaesthetization in young animals is quite safe
Benzodiazepines, pharmacokinetics
- Absorption = Oral absorption is good, IM is delayed onset
- Elimination = Via the kidney
Benzodiazepines, indications
- Premedication and combination (with ketamine)
- Muscle relaxation
- Prevention and control of epilepsy
- Sedation
