module 3 Flashcards
what is the general mechanism of sedative hypnotics
an increase in the GABA neurons which will decrease glutamate firing
explain GABA signalling
GABA can open select chloride channels which will release chloride ions which will make it harder for post synaptic neurons to transmit incoming signals , diminishing CNS signalling
explain the binding of sedative hypnotics to chloride
- modulate ion channel in brain or spinal chord , however each different drug will bind to a different site on the chloride channel –> enhance inhibitory effect of GABA
therapeutic effects of Benzodiazepines
relaxation , calmness, relief of anxiety and tension , decrease in REM type sleep, relation of skeletal muscles , some can be effective hypnotics
administration of benzodiazepines
taken as a tablet or capsule however could be intravenous
mechanism of action of benzodiazepines
increase the frequency of opening of chloride channel
how are benzodiazepines lethal ?
commonly involved in overdose, death can occur when large amounts are used or when taken with other sedation drugs
what is the antidote for benzodiazepines ?
flumazenil which is a receptor antagonist which will block the effects of benzodiazepine , can be used to reverse the effects (overdose )
short term adverse effects of benzodiazepines
CNS - fatigue, impairment of thinking and memory
LUNGS- respiratory depression
MOTOR COORDINATION- moderate doses can impair driving and motor coordination , will get worse as dose gets larger
Adverse long term use of benzodiazepines
varies with the individual, others will demonstrate symptoms of chronic sedative - hypnotic intoxication ( impaired thinking, disorientation , poor memory
benzodiazepines and pregnancy
result in fetal abnormalities if administered within the first trimester - also found in breast milk, could result in infant death
elderly and benzodiazepines
can produce cognitive dysfunction in older adults , are metabolized more slowly and cold result in over sedation
potential for misuse with benzodiazepines
have weaker reinforcing properties , with low harmfulness ( won’t lead to death on its own )
tolerance to benzodiazepines
can develop for the sedative effects and impairment coordination , level of tolerance is very low. ( cross tolerance can occur with other sedative drugs )
short and long term withdrawal of benzodiazepines
with therapeutic use, there is mild withdrawal symptoms ( headache ), chronic use , there are worse symptoms, such as paranoia, agitation and seizures
addiction to benzodiazepines
can occur however depends on environmental factors and genetics
Barbiturates
class of sedative hypnotics that are grouped by their duration of effect , long, short or ultra short. Barbituric acid is the base
Mechanism of barbiturates
increases the duration of of the opening of the chloride channel
low doses of barbiturates cause
tranquility and relaxation , and possibly induce sleep
short and ultra short barbiturates can be used for
induce anaesthesia
barbiturates have been replaced because ?
low therapeutic index and possibly could cause death ( depression of respiration , especially with alcohol, dose depend on person and there is no antidote
effects of short term barbiturate use
- mild euphoria, dizziness, mild impairment of motor coordination,
high doses, depresses cardiovascular system , slowing heart and blood pressure
long term effects of barbiturate use
chronic inebriation - impaired memory , judgement, and thinking
adverse effects of barbiturates
suppress the REM sleep
potential for misuse of barbiturates
should be avoided as it is the same as alcohol
- sometimes are injected to obtain rush effect—> very dangerous
tolerance of barbiturates
high degree of cross tolerance between other sedatives
withdrawal of barbiturates and symptoms
will occur after chronic use , symptoms include, seizures, delirium, high body temperature and hallucinations
postural hypotension is also seen
addiction of barbiturates
can result from regular use no matter the dose . people may panic if cannot get supply , and craving is common
zopiclone and zolpidem
benzodiazepine like drugs that bind to a subset of the GABA receptors and cause sedation
advantage of zopiclone
disturb sleep patterns less than traditional benzodiazepine
- they have more sedative effects compared to anxiolytic effects
Buspirone
anxiolytic that acts on serotonin receptor instead of GABA and can be prescribed when the patient is already taking a CNS depressant –> doesn’t have additive effects
where is alcohol absorbed ?
20% in the stomach and 80%in the upper small intestine
what affects the absorption of alcohol
- stomach emptying time and ethanol concentration in the GI tract and the presence of food
What are the 4 steps of alcohol metabolism
alcohol dehydrogenase, meos, aldehyde dehydrogenase and aldehyde dehydrogenase
what is alcohol dehydrogenase ?
the enzyme which is used to convert ethanol to acetaldehyde , is known as the rate limiting step
What is MEOS and what does it do ?
microsomal ethanol oxidizing system which is part of cytochrome p450 system
- contributes to the metabolism of ethanol , breaking it down to acetaldehyde when alcohol dehydrogenase is running at full capacity
acetaldehyde is converted to ?
acetate by the enzyme aldehyde dehydrogenase (ALDH)
Acetate is then metabolized to
CO2 and water by otters tissues
how do genetic variants contribute to ethanol metabolism ?
some ppl rapidly convert alcohol to acetaldehyde causing it to accumulate in the body ( protects agains alcoholism )
what is the rate of ethanol metabolism
occurs at a constant rate, irrespective of the blood alcohol concentration —> ADH becomes saturated at 20 mg per 100 ml of blood
body rate of ethanol metabolism is
120mg ethanol/ kg body weight / hour
how is alcohol excreted ?
95% of ethanol is eliminated via the liver, while the 5% is eliminated through breath, urine and sweat
alcohol is metabolized through
mainly the liver but some can happen in the stomach
build up of acetaldehyde causes
- nausea, vomiting, flushed face, dizziness
medical uses of alcohol
can be used as a skin disinfectant, as an antidote the treatment of methanol poisoning and also as a hand sanitizer and topically to treat fever
what will take place with a BAC of 0.1- 0.2 %?
impaired motor function , slurred speech, ataxia
what will take place with a BAC of 0.2-0.3%
emesis, stupor
what will take place at a BAC of 0.3- 0,4 %?
coma
BAC greater than 0.4%?
Death and respiratory depression
what is the main mechanism of alcohol ?
binds to the chloride ion channel and augmenting GABA mediated neuronal inhibition
alcohol interacts with ?
chloride ion channels in dopaminergic neurons in reward centres of brain ( could explain reinforcement )
Low doses and High doses of alcohol on cardiovascular system
LD - can create vasodilation of vessels which contributes to warmth feeling
HD- can lead to cardio depression which could alter the rhythm of the heart
Low dose and high dose of alcohol effect on stomach
LD- increase in gastric secretion
HD- will irritate the lining of the stomach and case immflamtion and gastritis , which causes vomiting
Low dose and High dose of alcohol on the liver
LD- does not have significant effects on the liver
HD- binge drinking will inhibit glucose production and can lead to hypoglycaemia
adverse effects of binge drinking include :
Memory loss , psychiatric effects ( depression irritability , and over sedation ) and overdose
adverse effects of chronic high dose alcohol consumption in the CNS include
neurological disorders such as alcoholic dementia, as alcohol can damage axons in the brain and will effect memory , judgement and thinking
Cardiovascular effects of chronic high dose alcohol consumption
- leads to alcoholic cardiomyopathy ( destruction of heart muscle ) and an increased incidence of hypertension and stroke
Liver and chronic high dose alcohol consumption
- leads to alcoholic lever disease which is irreversible at later stages and severely impairs liver function
chronic high dose alcohol and pregnancy effects
will manifest postnatally as fetal alcohol spectrum disorder (FASD)
features of FASD
flat mid face, short nose, the upper lip , short palpebral fissure, indistinct phillirum
what happens when alcohol is used in drug therapy
will have an additive or synergistic effect of CNS depression
- inhibition of metabolism of certain drugs ( sedative- hypnotics
what happens when there is chronic alcohol use before drug therapy ?
increases the activity of metabolizing enzymes in the liver resulting in increased metabolism
potential to misuse ethanol
has moderate misuse use potential due to its reinforcing properties. high availability contributes to possible misuse
inherent harmfulness of alcohol
moderate , ethanol is less harmful than methanol
tolerance to alcohol
can occur with chronic consumption
cross tolerance can occur with alcohol and
sedative - hypnotics –> higher dose would be needed to achieve therapeutic effect and general anesthetics –>a higher dose of anaesthetic would be needed for someone who developed tolerance to alcohol
withdrawal of alcohol
produces compensatory excitation of the CNS ( arousal stimulation ) with severe cases of withdrawal delirium tremens may occur which includes coma, tremors and possible death
addiction of alcohol
very powerful when there is chronic use of alcohol contributing to SUD
why is diazepam which is a benzodiazepine used to treat alcohol withdrawal symptoms
due to the similar mechanism of action to alcohol which is sued to suppress symptoms
what drug is used to treat
Naltrexone which is an opioid antagonist in which it diminishes the craving of ethanol and helps in abstinence and blocks the activation of dopaminergic reward pathways
cannabis contains
cannabis sativa, sativa and has 60 compounds known as cannabinoids ( THC is the most psychoactive agent)
pharmacological classification of cannabis
is a CNS depressant , euphoriant and hallucinogen
how is cannabis administered ?
it isa dried plant that is smoked or inhaled, extracts contain cannabinoids in oil that can be vaped or taken orally
Mechanism of a action of cannabis
binds to receptor in brain and spinal cord known as type 1 cannabinoid receptors (CB1)
Anandaminde and cannabis
is an endogenous ligand for CB receptors involved in learning and memory , when receptor is activated, it inhibits the release of excitatory neurotransmitters ( explains reduction of cognitive function with THC
anandamide is considered a
retrograde transmitter, meaning it is released from postsynaptic neuron and influences pre synaptic neuron and will bind to CB1 receptor, and inhibiting release of excitatory neurotransmitters
where are CB1 receptors located in Brain ?
CB1 receptors in cerebral cortex - mediate distortions of time and color and cognitive function
CB1 receptors in hippocampus - account for changes in memory and learning
CB2 receptors are found ?
outside of the CNS and are not involved in the psychoactive effects of THC
binding of THC to CB2 in lymphocytes is responsible for
immunosuppressive properties of THC
absorption of THC
Once inhaled, effects are almost immediate, if ingested, there is a 30 to 60 minute delay and and absorption is slow and incomplete
THC distributes where in the body ?
everywhere , however is higher in tissues with high blood perfusion ( lung , heart, brain and liver ) is highly lipid soluble and will be stored in adipose tissue over time
THC is metabolized ?
very slowly and will remain in the body weeks after use
THC excretion?
has a half life of around 30 hours but to remove from adipose tissues may take longer
short term use of THC and the CNS
Relaxation and drowsiness , feeling of well being an euphoria, impaired motor coordination, and increased appetite
with higher doses what can occur ?
pseudo- hallucinations where the person knows it is not real and running together of senses and impaired judgement
cardiovascular system and short term effects of THC
increased heart rate, increased blood flow to extremities and postural hypotension ( low blood pressure when standing or sitting )
GI tract and short term THC usage
increased appetite and dryness of mouth and throat
other possible shrort term effects of cannabis
reduction in sex drive for males ( decrease in testosterone), disruption of the ovarian cycle and hangover feelings
while driving, THC can impair ?
motor coordination, tracking, perception and vigilance
psychological effects of long term cannabis use
at a high dose, there can be short term memory loss, lack of concentration, loss of abstract thinking. Amotivational syndrome is associated with long term use can possibly have permenent structural changes in the brain with long term use
cardiovascular effects and long term use of THC
Some changes in blood pressure are seen as well increase in heart rate however are not serious and are reversible. could be an issue with heart disease
respiratory effects of long term use of THC
incidence of lung cancer and COPD are increased with long term use . can be damaging due to the high amount of carcinogens found in the cannabis smoke and the smoke is held in the lungs for longer causing more damage from higher absorption of tars
long term use of THC and fertility
can lead to decreased sperm count and FSH and LH will be reduced in which a cycle can occur without egg release , in pregnancy THC can readily cross the placenta causing possible delays in development
vaping and E cigarettes can cause ?
EVALI a unique disease entity the results in lung injury
medical use of cannabis needs to ?
separate the beneficial effects ( analgesia) from the psychotropic effects
when can cannabis be prescribed ?
not an approved heath Canada therapeutic but, can be used to treat a variety of symptoms that have not response to traditional treatment
misuse potential of cannabis ?
considered low to moderate as euphoria and reinforcement are lower compared to other drugs
tolerance of cannabis can occur for
the psychoactive properties of THC , the effects on the cardiovascular system and the impairment of cognitive function
withdrawal and cannabis
can occur with high dose long term use and can be characterized by sleep disturbances, irritability, nervousness , loss of appetite and sweating
addiction and cannabis
- develops as a persistent craving of a drug , risk is more evident in those that use it to control psychological stress
Opioids are found
within the opium poppy plant and clinically produces morphine and codeine
opioids can be
a natural or synthetic substance that will bind to opioid receptors
endogenous opioids are
opioids that are made in the body that bind to opioid receptors and exert analgesic effects . the 3 families are enkephalins, dynorphins and beta endorphins
- are able to affect perception of pain and the emotional response and could influence mood and are associated with reward pathways
The natural opioids are
morphine and codeine
Morphine binds directly to
opioid receptors and is used clinically to treat severe and chronic pain and can cause euphoria ( is 10x more potent than codeine )
codeine gets transformed into
morphine in the body by liver enzymes ( Tylenol is a combo of codeine and acetaminophen and caffeine )
semi synthetic opioids
altered versions of morphine to chemically give other pharmacological properties
hydromorphone
semisynthetic opioid that is used for analgesia and is 5x more potent than morphine
diacetylmorphine
aka heroin is a semi synthetic and is used as part of injectable opioid agonist therapy (iOAT) to manage OUD , 2- 5x more potent than morphine
synthetic opioids
not derived from morphine but are chemically synthesized to bind to opioid receptor
fentanyl and other related compound
100x more potent than morphine and was designed to treat acute chronic pain
loperamide
over the counter drug that is used to treat diahrrea ( uses a common side effect of opioids which is constipation , does not cause euphoria and is metabolized quickly in the intestine
methadone
Is used for analgesia and can be used in treatment of OUD as it can prevent withdrawal symptoms but will not cause euphoria
where are opioid receptors found ?
in both the central an peripheral nervous system and also in the GI tract
Mu opioid receptor
found in brain and spinal cord and mediate analgesia and are responsible for morphine mediated depression in brain stem –> often involved in the misuse of opioids
kappa opioid receptors
involved in analgesia, dysphoria and miosis (pinpoint pupils)
Delta opioid receptors
involved in analgesia in the spinal cord and brain and may modulate emotional responses to opioids
mechanism of action of opioid
will block pain pathways in spinal cord and brain through the activation of mu receptors
how do opioids reduce pain signalling
prevent pain signals from traveling by reducing neurotransmitter release from presynaptic neurons and reducing the effect on post synaptic neurons
opioids reduce emotional reaction through
modulation of the limbic system
Analgesia and opioids
a short term effect which produces indifference to pain reducing both the reaction and intensity of the pain , respiratory depression is the limiting factor
sedation and hypnosis and opioids
all opioid analgesics produce sedations but will not be as intense as cos depressants
suppression of cough centre and opioids
short term effect in which relief or prevention of cough
respiratory depression and opioids
a short term effect which surpasses the respiratory centre of the brain stem , respiratory drive of co2 is reduced mediated by mu and delta receptors , can cause death or overdose
short term endocrine effects and opioids
reduced release of testosterone , estrogen and progesterone and drop in libido for men reduce the release of sex hormones from hypothalamus
miosis and opioids
causes the constriction of pupils
body temperature/ heart rate and opioids
heart rate will be irregular with high dose of opioids and the skin will be cold and clammy
decreased motility
constipation is an adverse effect of short term opioid use
what are the 3 therapeutic uses of opioids
treatment of severe pain, treatment of diarrhea and cough suppression
misuse potential for opioids
have powerful euphoric effects which means there is a larger potential for misuse
inherent harmfulness of opioids
low moderate dose: not very high for morphine
high doses : can be life threatening
injection risk of opioids
higher risk of developing abcesses and injections ( heart valve ), using contaminated needles could spread AIDS or hepatitis
what happens with opioid overdose
takes place when there is profound respiratory depression , treatment includes opioid antagonist naloxone
tolerance of opioids
occurs with most pharmacological effects aside from constriction of pupils and the constipation, tolerance will be reversed a few days after usage stops
cross tolerance of opioids
occurs between all opioid analgesics where they act on the same receptor( tolerance to morphine will result in a tolerance to methadone )
withdrawal and opioids
pronounced withdrawal syndrome occurs after opioid discontinuation and symptoms include restlessness, anxiety, sweating, chills, increased respiratory rate , cramping and diahrrea
opioids addiction
pronounced craving for opioid can develop due to powerful euphoria
opioid in pregnancy
increased risk of premature delivery and low birth rate , at birth, baby will experience abrupt termination of opioid exposure which will lead to irritability, sleep disturbances poor feeding and seizures
pharmacological treatment of OUD and opioids
buprenorphine/ naloxone long acting synthetic opioid which binds to mu and provide enough agonist to prevent withdrawal symptoms but has decreased euphoria and sedating effects . In Canada the 2 are administered together
what is methadone ?
used for treatment of OUD and is a synthetic opioid that is effective in oral administration and is long lasting , potential of misuse is low and removes possible risks of injections . can lead to less euphoria due to the slow effects of taking it orally
