PHAR 100 - Module 3 Flashcards
sedative-hypnotics and anxiolytics
- are CNS depressants
- decrease glutamate-induced nerve firing
GABA signalling
- primary inhibitory neurotransmitter in the CNS
- causes inhibition by binding to and selectively opening chloride channels, resulting in hyperpolarization of the post-synaptic membrane of a neuron
- overall effect is that it is harder for the post-synaptic neuron to transmit incoming messages to other neurons, depressing overall CNS neuronal signalling
drugs that bind to the chloride channel
- most sedative-hypnotics:
- modulate the chloride ion channel in the brain and spinal cord
- result is an increase in synaptic inhibition and thus a dampening of neuronal responses
- in essence, they enhance the inhibitory effect of GABA
benzodiazepines mechanism of action
- activation of the benzodiazepine receptor increases the frequency of the opening of the chloride channel
benzodiazepine routes of admin
capsule, tablet or IV
benzodiazepine lethality
- commonly involved in overdoses
benzodiazepine pharmacological processes
- very high therapeutic index
- some members of this group are effective hypnotics
benzodiazepine short-term use
- CNS → relaxation, calmness, anxiety relief
- lung → respiratory depression
- motor coordination → can impair motor coordination
benzodiazepine long-term use
- impaired thinking, poor memory
- disorientation
- slurred speech
benzodiazepine abuse potential
- low abuse liability
- low inherent harmfulness
- margin of safety is high
benzodiazepine dependence
- tolerance → can develop to sedative effects; high degree of cross-tolerance occurs among other sedative-hypnotics
- dependence → low for short term use
- addiction → may develop for some
barbiturates
- potent CNS depressants
barbiturates mechanism of action
activation of the barbiturate receptor increases the duration of the opening of the chloride channel
barbiturates pharmacology
- possess a low therapeutic index
- suppress REM sleep
- depress respiratory system
barbiturates short-term effects
- mild euphoria
- dizziness
- sleep
barbiturates long-term effects
chronic inebriation
barbiturates abuse potential
- abuse liability is equal to or greater than alcohol
- inherent harmfulness is high due to risk of death from respiratory depression
barbiturates dependence
- tolerance → can develop to sleep induction and mood effects
- dependence → a withdrawal syndrome occurs (tremors, anxiety, insomnia, seizures, hallucinations)
- addiction → can result from regular use
flumazenil
- a benzodiazepine receptor antagonist that blocks the effect of benzodiazepines
- can be used as an antidote to benzodiazepine overdose
zolpidem
- bind to a subset of the GABA receptors, causing sedation
- disturb sleep less than benzodiazepines
buspirone
- acts at the serotonin receptor
- used in generalized anxiety states
- doesn’t have an addictive effect
gamma-hydroxybutyric acid (GHB)
- an agonist at a subset of GABA receptors, causing sedation and anesthesia
- implicated as a date-rape drug
ADME of alcohol → absorption
- overall rate for a given dose of ethanol is affected by: stomach-emptying time and ethanol concentration in GI tract and presence of food
ADME of alcohol → distribution
distributes throughout the total body water and readily gains access to the brain
ADME of alcohol → metabolism
- ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH)
- genetic variants in the gene that codes for ADH exist
- a 2nd pathway of ethanol metabolism is the microsomal ethanol oxidizing system (MEOS), which is part of the cytochrome P450 system
- the MEOS contributes to the removal of a dose of ethanol, especially at high doses
- acetaldehyde is then converted to acetate by aldehyde dehydrogenase (ALDH)
- acetate is further metabolized by a number of tissues into CO2 and water
- constant amount of alcohol is metabolized each hour
- ADH is rate-limiting
alcohol CNS effects
- CNS depressant
alcohol mechanism of action
- affects a large number of membrane proteins that particpate in signalling pathway
- augments GABA-mediated neuronal inhibition
alcohol non-CNS effects
- short-term (1-3 drinks) → vasodilation of skin vessels, increases gastric secretion
- short-term (5+ drinks) → depress cardiovascular system, irritation of stomach lining, inhibit glucose production
- adverse effects → blackouts, psychiatric effects, drinking and driving, violence
alcohol effects of chronic high dose
- CNS → alcohol dementia
- cardiovascular system → alcohol cardio myopathy
- liver → fatty liver, alcohol hepatits, cirrhosis
alcohol abuse potential
- significant reinforcing properties
- dependence liability is moderate
alcohol tolerance
- tolerance to chronic use of ethanol does occur
- cross-tolerance can occur between ethanol and sedative-hypnotics and general anesthetics
alcohol dependence
withdrawal from ethanol produces excitability of the NCS
drugs used to treat alcoholism
- disulfriam → inhibits hepatic aldehyde dehydrogenase, and results in aldehyde concentration if the person drinks ethanol
- naltrexone → opioid antagonist, diminishes craving for ethanol
- acomprosate → effects mang receptor systems
cannabis mechanism of action
- THC binds to receptors, located in the brain and spinal cord called type 1 cannabinoid receptors (CB1)
- anandaminde was determined to be an endogenous ligand for CB receptors
cannabinoid receptors
- 2 types of CB receptors exist
- a large number of CB receptors are in the brain
- THC is not a very effective agonist
cannabis pharmacokinetics
- THC is slowly metabolized
- inhalation is complete and fast
cannabis short-term use effects
- CNS → relaxation, drowsiness, euphoria, impaired judgement
- cardiovascular → increased HR and blood flow to extremities
- GI → increased appetite
- other effects → reduction in sex drive in males, can disrupt ovarian cycle
- cannabis and impaired driving → motor coordination impaired
cannabis long-term effects
- psychological → loss of short-term memory, lack of concentration, “amotivational syndrome”
- cardiovascular → usually reversible
- respiratory → asthma, lung cancer, COPD
- fertility → can decrease sperm count, FH and LH are reduced
medical uses of cannabis
- hard to separate beneficial effects from psychotropic effects
- can help with nausea, appeitite, neuropathic pain
cannabis abuse potential
- dependence liability is low to moderate
- inherent harmfulness is also low
cannabis dependence
- dependene → can occur with high-dose use
- tolerance → occurs to psychoactive properties and to impairment of performance and cognitive function
- addiction → develops with regular use
opiate
any drug derived from opium (ex: morphine, cocaine)
opioid
- any natural or synthetic substance which exerts actions on the body that are similar to those induced by morphine and that are antagonized by the drug naloxone
- include: opiates, substances structurally related to morphine
Mu opioid receptor
- mediate analgesia and are responsible for morphine-mediated depression of respiration in the brain stem
kappa opioid receptor
involved in analgesia, dysphoria, and miosis
delta opioid receptor
- involved in analgesia at the level of the spinal cord and brain
- may also modulate the emotional response to opioids
opioids mechanism of action
- morphine and other opioids block pain pathways in the spinal cord and brain
- exerted through activation of Mu opioid receptors
1. reduced presynaptic release of chemical transmitters that are mobilized by pain impulse
2. blockade of postsynaptic effect of these transmitters
3. activation of descending inhibitory pathways to block pain input
4. reduced emotional reaction to pain by acting on the limbic area of the brain
opioids effects of short-term use
- analgesia → reduce intensity of pain
- sedation and hypnosis
- suppression of cough centre
- respiratory depression → Mu and delta opioid receptors
- endocrine effects → reduction in testosterone, estrogens and progesterone
- miosis - constriction of pupils
- HR and thermoregulation → irregular HR, low body temp
- decreased GI mobility
opioids long-term effects
- physiological deterioration
- psychological impairment
opioids therapeutic uses
- relief of severe pain
- treatment of diaherrea
- suppression of cough
opioid abuse potential
- powerful euphoric and analgesic effects
- moderate inherent harmfulness`
oxycodone
- recently made as a tamper-resistant tablet
opioid dependence
- tolerance → occurs to most pharmacological effects
- dependence → pronounced withdrawal syndrome can occur, not life-threatening
- addiction → euphoric actions are powerful reinforcers
treatment of opioid use disorder
- buprenorphine/naloxone →long-acting synthetic opioid that acts as a partial mu opioid receptor agonist; prevents withdrawal syndromes, decreased euphoria; combined with naloxone to deter people from abusing it
- methadone → synthetic opioid that is effective following oral administration
