Pharma 7: Drugs Of Abuse Flashcards
What is in common with all dependence producing drugs
The activation of the mesolimbic dopaminergic neurons and increasing DA release from the nucleus accumbens
i. stimulate firing of A10 cells
ii. amphetamine, cocaine—> release DA or prevent its uptake
The mesolimbic dopaminergic pathway
REWARD PATHWAY
From ventral midbrain (A10 group) to the nucleus accumbens and limbic regions via the medial forebrain bundle
The effect of removing D2 receptors in transgenic mice
REMOVED THE REWARD SYSTEM
Ie administered morphine without reward without affecting dopamines effects
!they still experienced withdrawal—> D2 responsible for reward NOT withdrawal effects
Other mediators involved in DA mesolimbic pathway
5-HT
Glu
GABA
Habituation
When the drug is administered repeatedly, after it is stopped the patient experiences aversive effects
The effect of chronic administration of opioids and cocaine
Increase the activity of adenyl cyclase in regions like nucleus accumbens
The drugs of abuse on a neurochemical level
Opioids, cocaine—>increase AC—>compensates for the acute inhibitory effect of Drugs of Abuse on cAMP—>rebound increase of cAMP after the drug is terminated—>increase cAMP-dependent protein kinases—>increase excitability of cells
Explain tolerance and dependence
Narcotics
Morphine
Heroin
Fentanyl
Oxycodone
CNS depressants
Ethanol Barbiturates Anesthetics Solvents Glutethimide Methaqualone
Anxiolytic drugs
BZDs
Psychomotor stimulants
Methylxanthines including caffine
Nicotine
Cocaine
Amphetamine
Psychomimetic agents
Cannabinoids
LSD
Mescaline
Phencyclidine
Entactogens
Empathy, love emotional MDMA
ETHANOL/alcohol
MOA
Cns depressant (small, lipophilic)
Similar to volatile anesthetics—> causes increase in fluidity of lipid membranes
May act through specific membrane ion channels and receptors
Ethanol
Effects
Slurred speech, motor in coordination, increased self confidence and euphoria
Ethanol teratogenic
Impaired fetal development
Ethanol effect on liver
Stress—>sympathetic discharge—> causes increase release of fatty acids from liver
Combines with ethanol imposing metabolic load—>impaired fatty acid oxidation be
!fatty liver—> cirrhosis and liver failure
Drugs used to treat tolerance and dependence on ethanol
Disulfiram
Naltrexone
Acamprosate
Narcotics MOA
Inhibit AC
OPEN K CHANNELS
Close Ca channels
All together—> inhibit synaptic transmission
Currently, there is an epidemic of
Fentanyl overdose
Categories of CNS STIMULANTS
- Psychomotor stimulants
2. Psychomimetic drugs
Psychomotor stimulants
- Methylxanthines—> theophylline (tea), theobromine (cocoa) and caffeine (coffee, tea, cocoa)
- Nicotine
- Cocaine
- Amphetamines
Methylxanthies
Administration
Orally
Methylxanthines can be used to treat
Asthma
Effects on smooth muscles, cns, kidney and bronchial sm
Methylxanthines
MOA
Inhibit PDE therefore no hydrolozation of cAMP—> increase cAMP concentration
Some act as PURINE A2 RECEPTOR ANTAGONISTS—> smooth muscle relaxant
Caffeine actions
Decrease fatigue
Increase mental alertness due to stimulation of cortex
Positive inotropic and chronotropic effects
Diuretic
Caffeine
CAUTION
Avoid in pt with peptic ulcer
Pregnancy—> no more than 3 cups of instant coffee/day
Any more would increase risk of miscarriage
Caffeine side effects
Insomnia, anxiety, agitation if moderate dose
Emesis and convulsions in high dose
Arrhythmias in lethal dose
Nicotine
Adminsitration
Inhalation
Dependence and tolerance with nicotine
Increased activity of the mesolimbic DA pathway
Nature of nicotinic Ach receptors
Ligand gated channels
Nicotine
MOA
Acts on nAchR which is directly coupled to ion channel—> channel opens—> allows entry of Na, Ca—> entrance of Ca further opens voltage dependent Ca channels—> more Ca entry
This works to cause fast excitatory synaptic transmission at NMJ, autonomic ganglia
Desensitization and Nicotine
Chronic nicotine administering—> increase number of nAchR
Actions of nicotine
Improve attention and learning time
Reduces anxiety and tension
Nicotine poisoning
Biphasic nature
Ie starts with stimulatory effects like tachycardia and HTN that are followed by depressor effects like central resp paralysis, bradycardia and severe hypotension
Nicotine
Side effects
- Irritability
- Tremors
- Intestinal cramps
- Diarrhea
- Increased heart rate
- Htn
Symptoms of nicotine withdrawal
Irritability Anxiety Restlessness Difficulty concentrating Headaches Insomnia
Cocaine
Administration
Chewing
Snorting
IV
Cocaine
MOA
A-direct action:
Differential reuptake blockade of NA, 5-HT and ”DA” ie monoamine blockade into presynaptic terminal—> elevate synaptic concentrations
Reuptake block is accomplished by blocking their transporters
B-indirect action:
Acts indirectly on opioidergic, glutaminergic, GABAnergic
Cocaine as local anesthetic
Na channel block
Cocaine
Effects
- Increased mental awareness
- Euphoria
- Hallucinations
- Delusions
- Paranoia (stimulation of cortex and brainstem)
- Adrenergic f/f syndrome—> tachy, htn, pupillary dilation, peipheral vasoconstriction
Cocaine
Side effects
Anxiety Mental depression Appetite suppression Seizures Fatal cardiac arrythmias
Cocaine withdrawal symptoms
Physical and emotional depression
+agitation
Amphetamines
Administration
Iv, smoking, orally
Amphetamines
MOA
- Promotes release of NA from central adrenergic receptors into synaptic cleft
- At DA neuron: increases DA at cleft
i. Bind to DA reuptake transporter—> reverse action—> transport of free Da into cleft
ii. Amphetamine taken up into cell—> DA released into synapse
iii. Amph diffuses into vesicle—> Da released into nerve terminal
Amphetamines
Effects
- Stimulate cerebrospinal axis ie cortex branstem
- Increased alertness
- Decrease fatigue
- Depress apetite
- Insomnia
- At high dose—> convulsions
- Indirect sns stimulation
Amphetamines
Side effects
Insomnia
Panic states
Amphetamine psychosis—> similar to schizophrenia attack when taken chronically
Palpitations
Cardiac arrhythmia
Suicidal tendencies
Irritability
Psychomimetic drugs/hallucinogens
Primary action
Induce altered states that resemble dreams—> changed thought patterns—> cant make decisions
Psychomimetic drugs
Tetrahydrocannabinol
Phencylidine
LSD
Mescaline
Psilocybin
Cause sensory changes, hallucinations and delusions (similar to acute schizophrenia)
Tetrahydrocannabinol (THC)
Main active substance of cannabis
*cannabis, morphine—> metabolically active metabolites
Cannabinoids action
Depressant and psychotomimetic actions
Alters mood, cognition
Cannabinoids
Administration
IV
Smoking
Cannabinoids structure
Highly lipid soluble
Anandamide
AA’
ENDOGENOUS LIGAND FOR CB1
Cannabinoids receptors
CB1 (brain; hippocampus, cerebellum sn and mesolimbic system) and CB2 (periphery; mainly lymphoid)
G protein coupled receptors
CB1–> inhibit AC….activate K conductance,,decrease Ca—> inhibit synaptic transmission
Analgesics?
Cb1 and ch1-paf
Cannabinoids effects
Euphoria Relaxation Sharpened sensory awareness Impaired memory, learning, motor Reduces IOP—> used in glaucoma Increases appetite
Analgesic, antiemetic—> NABILONE
Cannabinoids vs opiates, nicotine, alcohol
Less likely to cause dependence
No resp, cv effects if OD (only drowsiness, confusion)there4 safer
Cannabinoids
Side effects
Long term psych effects—> schizophrenia, apathy, under achievement
Low doses—> sensory distortion, hallucinations—
LSD
Potent hallucinations and delusions—> violence
“Flashback hallucinations” long after drug was taken—>psychopathalogic changes
If susceptible—> lsd and phencyclidine—> schizophrenic attacks
