Drugs of Abuse Flashcards
Abuse, addiction, physical dependence, withdrawal symptoms, tolerance?
Abuse - excessive self-administration
Addiction - drug seeking behavior
Physical dependence - associated with withdrawal symptoms
Withdrawal symptoms - physiological and behavioral changes related to sudden cessation of a drug which the body has become adapted to
Tolerance - adaption state where exposure results to diminution of drug effects over time
Mechanisms of addiction?
Increased stimulation of mesolimbic dopamine pathway leading to increased dopamine release
Ethanol?
CNS depressant that leads to sedation and sleep. Initial effects of ethanol can be perceived as stimulation due to suppression of inhibitory systems.
MOA…
- GABAa receptor
- Kir3/GIRK channel
- Adenosine re-uptake
- Glycine receptors
- NMDA receptors
- 5-HT3 receptors
Withdrawal symptoms due to tolerance and physical dependence…
- tremor, nausea, vomiting, sweating, agitation
- anxiety
- hallucinations
- generalized seizures after 24hrs
- delirium tremens after 48 hrs
How do you treat alcohol withdrawal?
Diazepam and chlordiazepoxide - long half-life benzos b/c they prevent rebound withdrawal symptoms
In elderly and people with liver failure - it is better to administer intermediate-acting drugs, Lorazepam and Oxazepam - these go straight to phase II glucuridation so put less stress on the liver
How do you treat alcohol addiciton?
- Disulfiram - aldehyde dehydrogenase inhibitor - creates aversion to drinking
- Naltrexone - orally available opioid antagonist -reduces alcoholic craving
- Acamprosate - NMDA receptor antagonist - prevents relapse
- Topiramate - facilitates GABA function and antagonizes glutamate receptors - this may reduce cravings, but is not FDA-approved for this indication
Benzo withdrawal symptoms?
Benzodiazepines cause physical dependence and addiction (addiction is very rare though). Withdrawal symptoms include tremors, anxiety, perceptual disturbances, dysphoria, psychosis and seizures – these are life-threatening!
**barbiturates have abuse problems that resemble benzos
How do you manage benzo withdrawal?
If patient is on short-acting drug, switch them to long-acting drug. – use Diazepam and then gradually reduce dose until pt is free from dependence
Psychostimulants?
- Methylxanthines
- Cocaine
- amphetamines
Methylxanthines?
Caffeine, theophylline, Theobromine – caffeine is the most widely consumed stimulant – these substances block presynaptic adenosine receptors. Normally the adenosine receptors inhibit NE release, so blocking the receptors potentiates the NE release therefore acting as a stimulant. Adenosine is also a natural promoter of drowsiness, so by blocking adenosine receptor there is a potential of insomnia.
CNS actions…
100-200mg caffeine - decrease fatigue and increase mental alertness
1.5g caffeine - produces anxiety and tremors
2-5g of caffein - spinal cord stimulation
Methylxanthines tolerance and withdrawal?
Tolerance can rapidly be developed to the stimulating properties of caffeine and withdrawal consists of fatigue and sedation. Addiction is very rare and not considered in the category of addicting stimulants.
Cocaine?
Schedule II drug that inhibits dopamine, NE and serotonin reuptake. The prolongation of dopaminergic effects in the brains’ limbic system produces the intense euphoria that cocaine initially causes.
CNS - stimulation of cortex and brainstem increasing mental awareness and euphoria - paranoia may occur after repeated doses - high doses cause tremor, convulsions followed by respiratory depression
SNS - peripherally cocaine increases NE action resulting in adrenergic stimulation producing tachycardia, HTN, mydriasis and diaphoresis
Cocaine withdrawal syndrome?
- Dysphoria, depression, sleepiness, fatigue, cocaine craving and bradycardia.
- Cocaine withdrawal is generally mild.
- Treatment of withdrawal symptoms is usually not required
Amphetamines?
Schedule II drug that increases release of catecholamines, weak inhibitors of MAO and have a possible direct effect on catecholamine receptors.
CNS 0 similar to cocaine due to release of DA, increased alertness, decreased fatigue, depressed appetite, insomnia, high doses produce psychosis and convulsions
SNS - activate receptors through NE release
Uses…
- ADHD - amphetamine, methylphenidate
- Narcolepsy - amphetamine, methylphenidate
Marked tolerance that may result in withdrawal post abstinence. Symptoms include increased appetite, sleepiness, exhaustion, mental depression.
Nicotine?
Second only to caffein as the most widely used CNS stimulate and the second most abused as well to alcohol.
MOA - fill agonsit of nicotine receptors stimualting rewarding effect involving VTA increasing dopamine release. At low doses there is ganglionic stimulation by depolarization and at high doses there are ganglionic blockades.
CNS
• Cigarette smoking or administration of low doses
of nicotine produces some degree of euphoria
and relaxation.
• Improves attention, learning, problem solving,
and reaction time.
• High doses of nicotine result in central
respiratory paralysis and severe hypotension
caused by medullary paralysis.
• Nicotine is an appetite suppressant
Nicotine withdrawal symptoms and addiction tx?
Withdrawal symptoms..
• Nicotine withdrawal is mild.
• Involves irritability and sleeplessness.
• However, nicotine is among the most addictive
drugs.
• Relapse is very common.
Nicotine addiction tx..
- nicotine replacement therapy - transdermal patch, gym, nasal spray, etc
- sustained-release bupropion
- Varenicline - partial agonist at nicotinic receptors in CNS
