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Flashcards in Drugs of Abuse Deck (24):
1

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

2

Mechanisms of addiction?

Increased stimulation of mesolimbic dopamine pathway leading to increased dopamine release

3

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...
1. GABAa receptor
2. Kir3/GIRK channel
3. Adenosine re-uptake
4. Glycine receptors
5. NMDA receptors
6. 5-HT3 receptors

Withdrawal symptoms due to tolerance and physical dependence...
1. tremor, nausea, vomiting, sweating, agitation
2. anxiety
3. hallucinations
4. generalized seizures after 24hrs
5. delirium tremens after 48 hrs

4

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

5

How do you treat alcohol addiciton?

1. Disulfiram - aldehyde dehydrogenase inhibitor - creates aversion to drinking

2. Naltrexone - orally available opioid antagonist -reduces alcoholic craving

3. Acamprosate - NMDA receptor antagonist - prevents relapse

4. Topiramate - facilitates GABA function and antagonizes glutamate receptors - this may reduce cravings, but is not FDA-approved for this indication

6

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

7

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

8

Psychostimulants?

1. Methylxanthines
2. Cocaine
3. amphetamines

9

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

10

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.

11

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

12

Cocaine withdrawal syndrome?

• Dysphoria, depression, sleepiness, fatigue, cocaine craving and bradycardia.
• Cocaine withdrawal is generally mild.
• Treatment of withdrawal symptoms is usually not required

13

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...
1. ADHD - amphetamine, methylphenidate
2. Narcolepsy - amphetamine, methylphenidate

Marked tolerance that may result in withdrawal post abstinence. Symptoms include increased appetite, sleepiness, exhaustion, mental depression.

14

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

15

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..
1. nicotine replacement therapy - transdermal patch, gym, nasal spray, etc
2. sustained-release bupropion
3. Varenicline - partial agonist at nicotinic receptors in CNS

16

Most commonly abused opioids?

The most commonly abused opioids are heroin,
morphine, codeine and oxycodone, and –
among health professionals- meperidine and
fentanyl.
-short acting opioids are usually imcompatible with a productive life due to increased need of consumption of the drug (ex. heroin)
-withdrawal symptoms are unpleasant (dysphoria, lacrimation, rhinorrhea, yawning) but not life threatening

17

How do you tx opioid withdrawal?

1. Replace with long-acting opioid then slowly reduce dose -- methadone and buprenorphine are the most commonly used
2. Detox with adrenergic agonists - Clonidine and Lofexidine [both are a2 agonist] that prevent the rebound firing of the adrenergic neurons that occur with the withdrawal symptoms
3. Naltrexone - opioid antagonist with high affinity to mu opioid receptors that do not satisfy craving but rather relieve withdrawal symptoms

18

Marijuana?

There are 61 different cannabinoids in marijuana but delta9-THC produces the most effects. THe two cannbinoid receptors that produce the most effects are CB1 and CB2 which are Gi coupled.

CB1 - found in brain mediates psychological effects
CB2 - found on immune cells

Actions
1. produces euphoria followed by drowsiness and relaxation
2. affects short-term memory and mental activity
3. impaires skilled motor activity
4. appetite stimulation, xerostomia, visual hallucinations, delusions, enhancement of sensory actigity
5. at high doses - toxic psychosis

Therapeutic THC - dronabinol which is approved as an anti-emetic and appetite stimulant

19

LSD?

LDS, mescaline, psilocybin - actions mediated by 5-HT2 receptor agonist in the CNS. Pts present with a combination of somatic (sympathomimetic effect - HTN, tachycardia, increased body temp, flushing, sweating, tremors, piloerection) and psychomimetic symptoms.

LSD - no addiciton, no withdrawal

AE - possibility of "bad trips," may cause severe agitation needing tx (with diazepam)

20

PCP (phencyclidine)?

Dissociative anesthetic that blocks reuptake of NE and Dopamine and also has cholinergic AND anti-cholinergic effects as well as actions at nicotinic and opioid receptors. On top of all of this the causes of dissociative anesthetic are actually mediated by non-competitice antagonist of NMDA receptors.

Clinical manifestations - violent behavior, psychosis, NYSTAGMUS, tachycardia, HTN, diaphoresis, miosis, anesthesia, analgesia

Intoxication tx - no antidote for PCP, but the violent psychotic behavior and seizures are managed by parenteral benzos

21

MDMA ("ecstasy")?

Produced feelings of empathy and intimacy without impaired intellectual capacities mediated by the increase of serotonin in the synaptic cleft. Withdrawal is characterized by depression lasting for a few weeks.

22

Nitrous oxide?

Produces euphoria and analgesia followed by loss of consciousness. Usually taken as 35% N2O mixed with O2. If 100% N2O is given, it leads to asphyxia and death.

23

Inhalants?

1. volatile organic solvents - gasoline, paint thinners, lighter fluid, glue, degreasers - cause exhilaration and light headedness - may lead to cancer, cardiotoxicity, neuropathies and hepatotoxicity

2. Organic nitrates - amyl nitrite and butyl nitrate used to enhance erection - not addictive

24

Anabolic steroid?

Used to increase muscle size by body-building competitors.