Nicotine And Psychostimulant Abuse Flashcards
psychomotor stimulants
MOA: all increase activity of the CNS
- leads to excitement, euphoria, increase motor activity and feelings fatigue
Therapeutic indications for stimulants
ADHD
Narcolepsy
Anorexiant (suppress hunger)
OSA
Nicotine MOA
Agonists at the neuronal nicotinic receptors
- there are 16 in the autonomic ganglion, therefore a lot of ADRs and effects occur here
- there is 1 nicotinic receptor type in the neuromuscular junction*
- concentrations >200nM (normal smoking of cigarettes), nicotine has higher affinity at neuronal nicotinic receptors*
- more affinity for Nm Receptors in higher concentrations
has dose dependent stimulation (low doses) or inhibition(high doses) effects
Symptoms of higher vs low doses of nicotine
Low doses = euphoria, arousal, relaxation
- activates within normal limits
- activation/stimulation of nicotinic receptors
High doses = tremors, convulsions, arrhythmias
- activates well outside normal limits
- down-regulation and desensitization of nicotinic receptors
- adrenal medulla effects:
- small doses = releases catecholamines (NE/E)
- large doses = disables release due to inhibitory stimulation of splanchnic nerves*
Other than CNS/PNS/medulla and NMJ, where else are nicotinic receptors seen?
Mechanoreceptors in:
- skin
- mesentery
- tongue
- lung
- stomach
Chemoreceptors in the carotid body
Thermal receptors in the skin/tongue
Pain receptors
Respiratory depression
Occurs in overdose of nicotine by paralysis of the CNS and the NMJs of the diaphragm and intercostal muscles
Cardiac effects of nicotine
In high doses = Vasoconstriction, tachycardia, HTN
effects are largely mediated by sympathetics
GI tract and urinary system effects of nicotine
Nausea/vomiting
Diarrhea
Bladder voiding
effects are predominantly parasympathetic
also increase emesis due to stimulation of vagus and area postrema in the medulla oblongata
Acute nicotine toxicity
Fatal dose = 40-50 mg
- roughly two- three cigarettes if digested
- 40-50 cigarettes if smoked
OD effects: - CNS = convulsions/coma/respiratory arrest (tx = diazepam) - Respiratory paralysis (tx = mechanical ventilation) - HTN/cardiac arrhythmias (Tx = atropine and wait out)
needs to survive first 4 hrs and have oxygen in brain at all times. If this occurs, near 100% chance to survive
Pharmacokinetics of nicotine
Metabolizes via CYP2D6 and glucuronidation
Induces CYP1A2 and CYP2E1
- metabolizes caffeine and alcohol easier*
Ways to use tobacco in order of how fast they reach peak concentration in blood:
1) cigarettes (5 min and 15 mg)
- metabolize very quickly though
2) snuff (10 minutes and 15 mg)
- metabolizes slower
3) chewing tobacco (60 minutes and 15 mg)
- metabolizes slower
4) nicotine gum ( 30 minutes and 7 mg)
- metabolizes slowest
What kind of learning theory is used in smoking?
Positive reinforcement that is reinforced over 200 times a day on average
- makes extinction very challenging
Nicotine withdrawal
low blood levels of nicotine = cravings to smoke
Symptoms
- anxiety
- dysphoria/ depressed mood
- difficulty in concentration
- restlessness
- tachycardia
- increased sedation and weight gain
First-line therapies for nicotine cessation
Nicotine replacement therapies
- gum, inhaler, lozenge, nasal spray, patch
Sustained release via bupropion patch
- antagonist of NAChRs
Varenicline (partial agonist and full agonist of nicotine receptors) use
- depends on receptors it hits, and can cause increase suicidal thoughts and vivid nightmares
- also increases cardiovascular risks
Counseling and motivational therapy
not first line but rimonabant (inverse agonist of CB1 receptors) is experimental for smoking cessation
Cocaine MOA
Blocks DAT and NET reuptake receptors
- increases dopamine in reward circuitry
- increase NE in cortiolimbic system
- *also indirectly increases 5-HT levels as well
Effects of cocaine
Low doses:
- increased arousal/attention
- increased self-confidence
- euphoria (30 min only)
- dose dependent tachycardia and BP
- decreases fatigue
High doses:
- seizures
- cardiovascular complications
- increased risk of self-induced trauma
- risky sexual behavior
Chronic use:
- anxiety/depression/paranoia
- irritability and increased aggression
- psychosis
- involuntary motor activity
- stereotyped behavior (moves predictably based on situation)
Acute cocaine toxicity symptoms
Psychiatric complaints
- paranoia and delusions/psychosis
Seizures
Hyperthermia (#1 cause of death)
Chest, heart and pulmonary pains
Treatment =
- benzos (calms patients and treate hyperthermia)
- symptomatic treatments
- group and individual psychotherapy
Cocaine metabolism
Hydrolysis by tissue esterases
- results in benzoylecgonine metabolite (which can be tested for in urine)
Cocaine and ethonal abuse together
- cocaine is metabolized to cocaethylene (essentially another dose of cocaine)
- OD is very likely
Ways to take cocaine:
smoked
Snorted
Ingested
Cocaine withdrawal symptoms
Dysphoria
Depression/sleepiness/fatigue
Cravings
Bradycardia
symptoms gradually go away over 1-3 weeks and are usually mild
challenge is to prevent resumption of binge cocaine use. This can lead to increased risks of OD
Amphetamines MOA
Both inhibits VMAT receptor and reverses the transport of DAT and NET receptors
- DAT and NET-receptors now efflux dopamine and NE out into presynaptic clef
This leads to mass elevation of dopamine NE and mass depletion after about 24 hrs
- toxic and withdrawal effects are worse as a result
Physiological effects of amphetamines
Simulates entire cerebrospinal axis, cortex, brainstem, medulla
- this is why its used in performance enhancing
Symptoms
- increased alertness
- decreased fatigue and appetite
- insomnia
- elevates BP and Bradycardia
- urine retention
- tachypnea
High doses
- cardiac arrthymias
Acute toxicity of amphetamines
Is more dangerous than cocaine
Symptoms
- Euphoria
- hyperthermia (fatal if left unchecked)
- insomnia
- aggression and paranoia
- tachycardia HTN and strokes
- tremors
- seizures/ convulsions (fatal if left unchecked)
Treatments:
- benzos (seizures and hyperthermia)
- symptomatic treatment
Amphetamine withdrawal
Symptoms:
- depression
- AMS
- sleep disturbances
- extreme for fatigue
Treatment:
- supportive only and symptomatic
- very rarely fatal though*
Note: CANT use TCAs for depression since it increases CV event risks (which amphetamines do by themselves)
Amphetamine therapeutic indications
ADHD
Narcolepsy
Off-label uses: (low doses ONLY)
- AIDS/MS/dementia
- fibromyalgia
- dysthymia
- obesity
- depression
What class of antidepressants are contraindicated for depression seen in amphetamine withdrawal?
TCA’s
- high risk of CV events
