2-18 Drug Tolerance / Abuse / Dependence Flashcards

Question

_Opioid Patterns of Use:_ Heroins' effects last about _____ hours. The average addict uses heroin _____ X per day. Tolerance and physical dependce develop\_\_\_\_ [slow/gradual/fast]. How does this affect the use of heroin, in terms of frequency and quantity?

Answer 1

_Opioid Patterns of Use:_ Heroins' effects last about **3-5 hours.** The average addict uses heroin **2-4 X per day**. Tolerance and physical dependce _develop gradually_, leading to both frequency and quantity of drug consumed.

Answer 2

Signs of Opioid Overdose: Unconsciousness MIOSIS (pinpoint pupils) Hypotension Bradycardia **\*Respiratory depression\*** **\*Pulmonary edema\*** **_Respiratory depression_ and _pulmonary edema_ are the two leading causes of death in an opioid overdose**

Answer 3

Heroin is a **PRO-DRUG** that is rapidly converted into **6- monoacetylmorphine** by **esterases** present in _blood, brain and most tissue._ This metabolite is further metabolized to **morphine,** _which contributes to the duration of the effect of heroin_.

Answer 4

_Pharmacokinetics of Heroin:_ Cross-tolerance = tolerance to one opioid is usually associated with tolerance to other opioids Withdrawal begins **12 hours** after last dose, peaks at **5-7 days** and is mostly over by **1.5-3 days;** yet lingering symptoms called the **P****rotracted Abstinence Syndrome**, can persist for months and are associated with relapse.

Answer 5

Anxiety Dysphoria Craving and drug-seeking Sleep disturbances N/V Diarrhea **Lacrimation** **Rhinorrhea** **Yawning** **Piloerection/gooseflesh (cold turkey)** Sweating, chills Mydriasis (excessive pupil dilation) Cramps Hyperpyrexia **involuntary movements "kicking the habit"** **\*Opioid specific symptoms: lacrimation, rhinorrhea, yawning, piloerection/gooseflesh, involuntary movement**

Answer 6

1. Self-help groups such as Narcotics Anonymous 2. Inpatietn detoxification facilities/residentials 3. Pharmacotherapy CHALLENGES * \*Individual therapy rare largely due to sociodemographic characteristics of users* * \*Dependence on prescription opioids presents a new challenge for treatment*

Answer 7

- Cure of withdrawal or overdose - Improve the holding power of outpatient treatment - to reduce drug cravings - to create a window of opportunity during which patients can receive psycho-social intervention to decrease the risk of relapse - to serve as short or long-term maintenance againts for patients who can't function without them but can lead productive lives with them

Answer 8

_Treatment approaches of opioid overdose and withdrawal syndrome:_ Treatment of opioid OVERDOSE with **naloxone, u-opioid R antagonist** Treatment of opioid DEPENDENCE with: **Naltrexone [Vivitrol], u-opioid R antagoinst** Treatment of opioid WITHDRAWAL with: **Methadone, u-opioid R *agonist*** OR **buprenorphine, partial u-opioid R *agonist***

Answer 9

**Naloxone** [Narcan, Nalone] is used for opioid overdose, Is a **u-opioid competitive antagonist** with **HIGH AFFINITY** and **SHORT HALF-LIFE** Acts within **2 minutes,** and duration of action is **~45 minutes,** which is MUCH SHORTER THAN HEROIN. *Due to this, what is important to do while treating individuals with opioid overdose?* Should be kept under observation for the duration of the opioid drug's effects to determine if additional antagonist treatment is needed (ie - heroin can occupy the opiod receptors again when action of Naloxone is over)

Answer 10

_Nalterxone [Vivitrol], is used to treat opioid dependence_ Is a u-opioid antagonist with **LONG half-life** Absorbed ORALLY **HIGH receptor affinity** What effect does Nalterxone have on the effects of heroin? heroin is no longer rewarding When should this drug be avoided? **AVOID IN PT WITH LIVER FAILURE**

Answer 11

Methadone, is one of the drugs used for opioid withdrawal it is a u-receptor agonist with **LONG half-life** of **15-60 hours!** Administered orally Lasts about **24 hours** _What does methadone therapy accomplish?_ **Prevents withdrawal symptoms and cravings** *due to its long half life* (will out compete heroin at receptor sites), and has **cross-tolerance** with other opioids _What is a draw back of using Methadone?_ it is only dispensed at federally licenced clinics and requires almost daily clinci visits even for individuals with long-term success

Answer 12

HIGH affinity for receptors and dissociates SLOWLY --\> long acting

Answer 13

Buprenorphine was abused, thus when sold in combo, it will result in withdrawal symptoms due to the presence of Naloxone (u-opioid receptor antagonist), thus less likely for someone to abuse treatment. If buprenorphine is initiated prior to the onset of acute withdrawal signs, it may lead to abrupt withdrawal syndrome due to displacement of full agonist (ie - heroin), for u-opioid receptor by buprenorphine

Answer 14

Delta-9-tetrahydrocannabinol (THC)

Answer 15

**THC** i_nhibits GABAergic interneurons_ by acting on **CB1** **receptors** --\> inhibiting the inhibitor--\> **INC DOPAMINE** release @ **nucleus accumbens** *cannabinoids cause disinhibition of mesolimbic DA system*

Answer 16

Sedation / relaxation Mood alteration, sense of well-being Altered perception and time estimation Impaired judgment, memory and concentration INC heart rate Dry mouth **INC appetite "munchies"** *(due to drop of sugar levels and also stimulation of cannabinoid R in the hypothalamus)* **Injection of the conjunctiva**"red eyes" (*due to decreased pressure in the eyes and increased blood pressure)*

Answer 17

Panic, delirium, paranoia, Amotivation syndrome, inattention, poor judgement, distractibility leading to accidents and misbehavior Tolerance occurs but physical dependence remians controversial Personality cahnges and cognitive deficits (loss of short-term memory) GATEWAY to other drug abuse Criminal or workplace sanctions

Answer 18

What is used to treat the following syndromes of marijuana abuse: Anxiety and panic --\> anxiolytics Delirium and paranoia --\> antipsychotics Dependence --\> CBT Is there any pharmacotherapies for marijuana abuse? NO but discovery of CB1 R and development of an antagonist is promising

Answer 19

Excessive alcohol consumption costs the US billions of dollars annually and millions of dollars on individuals due to speciality services, medical consequences, lost present and future earnings, accidents and criminal justice system.

Answer 20

~ 50% of the risk is attributed to genetics, yet many individuals may not even have family history and thus misuse is a result of environmental factors

Answer 21

_Type A Alcohol Dependence:_ 75% of alcoholics are Type A Onset: LATE \>25 y/o Familial alcohol-dependency: FEW Disease progression rate: SLOW Alcohol dependence: milder form Environmental influence: IMPORTANT Relation to criminality? minimal Response to treatment? better response than Type B

Answer 22

_Type B Alcohol Dependence:_ Onset? EARLY (less than 25 y/o) Familial alcohol-dependency? PATERNAL type B alcohol depend. Disease progression rate: quicker Alcohol dependence? MORE SEVERE FORM Environmental influence? minimal Relation to criminality? FREQUENT Response to treatment? not as good as Type A What other pychiatric disorder is frequently present? **personality disorder**

Answer 23

_What are primary diseases associated with chronic use?_ alcohol poisoning, alcoholic heart disease (CARDIOMYOPATHY), alcoholic gastritis, alcoholic liver cirrhosis, alcoholic nerve disease (polyneuropathy), alcoholic psychoses _What are secondary diseases associated with chronic use?_ (6) Cancer (lip, mouth, pharynx, esophagus, larynx, liver stomach), diabetes, GI disease, heart disease (HTN, stroke), liver disease, pancreatitis (acute. chronic)

Answer 24

_DOPAMINE SYSTEM_: Alcohol _indirectly_ INC DA levels in the mesocorticolimbic system --\> positively reinforcing effects (probaly of alcohol) _OPIOID_: alcohol can indirectly INC dopamine by activating the mesocorticolimbic system

Answer 25

**INC** the effects of GABA, the major INHIBITORY NT in the brain --\> feelings of relaxation and sedation Chornic exposure of alcohol leads to a DECREASE in the levels of GABA-ergic receptors

Answer 26

Acutely, alcohol intake **DEC** the effects of glutamate, the major EXCITATORY NT in the brain --\> decreased anxiety and increased sedation Chronic exposure to alcohol leads to an UPregulation of NMDA receptors Leads to **tolerance** and **dependence** ***balances the acute alcohol effects***

Answer 27

SUDDEN reduction in chronic alcohol intake leads to **OVERactivation of NMDA system**? Acutely --\> dysphoria, hallucinations Post-Acute --\> sleep and mood disturbances

Answer 28

1. Identification 2. Detoxification/Withdrawal 3. Rehabilitation 4. Adherence

Answer 29

Relieve immediate symptoms of withdrawal with **_benzodiazepines_**, which are indirect agonist for GABA receptors Benzos with LONG half-lifes (diazepam/valium) have less chance of recurrent withdrawal **_Lorazepam/Ativan_** has a short half life but it is NOT metabolized by the liver, so good for patients with cirrhosis

Answer 30

**6-36 hours after last drink --\> Minor Withdrawal** * CNS hyperactivity, HYPERAROUSAL* * Mild anxiety, H/A, sweating, palpitations, GI upset, insomnia, nausea* **6-48 hours after last drink --\> Seizures** ***\*\*CAN BE MOST LIFE THREATENING\*\**** 3% of chronic alcoholics can develop tonic-clonic seizures, some develop status epilepticus (seizures withouth regaining consciousness for 30 minutes) **12-48 hours after last drink --\> Alcoholic Hallucinations** visual, auditory or _TACTILE_ **48-96 hours after last drink, can last 5 days --\> Delirium Tremens**

Answer 31

**5%** of alcohol withdrawal leads to delirium tremens, and mortality can be up to **35 %** when left untreated. _Sx:_ confusion, disorientation, hallucinations, uncontrollable tremors of extremities, severe autonomic instability (*fever, tachy, HTN, diaphoresis)* _Treatment:_ Long half-life benzos (diazepam, lorazepam), and pharmacotherapy is symptomatic and supportive

Answer 32

**Disulfiram**- alcohol aversion therapy **Naltrexone**- long-acting opioid antagonist **Acamprostate**- restores balance between neural excitation and inhibition (mechanism unknown) *\*DNA\**

Answer 33

*High levels of acetaldehyde leads to (5):* nausea, dizziness, H/A, hypotension, vomiting Disulfiram **inhibits aldehyde dehydrogenase (ALDH)** that leads to increased high levels of acetaldehyde when taken with alcohol --\> decreases desire to drink alcohol but _does not increase abstinence_ INC risk for **hepatotoxicity**

Answer 34

Naltrexone MOA: anatgonist of opioid receptors, blocks release of DA from nucleus accumbens --\> REDUCES alcohol cravings When should Naltrexone be avoided? Liver disease, or patients dependent on opioids (can percipitate actute withdrawal syndrome) What drug should you not take with Naltrexone? DO not take with DIsulfiram (both hepatotoxic)

Answer 35

_Acamprosate_ _MOA:_ UNKNOWN _Overall effect:_ decreases excitatory glutamate NT and increases GABA-ergic activity _Minor side effects:_ Diarrhea, allergic reactions, irregular heartbeats _Contraindicated_: severe renal disease, dose adjustments in patients with moderate renal disease (when creatinine clearance 30-50 mL/min)

Answer 36

Bezodiazepines are INDIRECT AGONIST of the GABA receptors Used for: Severe anxiety, panic attacks and phobias Insomnia Muscular disorders- effective muscle relaxants Alcohol withdrawal Epilepsy (anticonvulsant)

Answer 37

Anxiety, agitaiton INC sensitivity to light and sound Muscle cramps Sleep disturbances Dizziness Mycolonic jerks Withdrawal managemetn: treat with diazepam, benzos with a long-half life, gradually tapering off the drug ove a period of months

Answer 38

ONE OF THE MOST ADDICTIVE DRUGS **Selective agonist of the nicotininc acetylcholine receptor** (nAChR), --\> simualtes dopaminergic neurons in the VTA and increases teh release of dopamine in the nucleus accumbens _Treatment:_ Nicotine patches, nasal spray, nicotine lozenge **Varenicline** [chantrix] = non-nicotonic medication, partial agonist that binds subunits of nicotine ACh receptors. Because it stimulates the receptors, it relieves cravings and withdrawal symptoms during abstinence from smoking. Binds to the nACh receptors with GREATER AFFINITY than nicotine --\> reduces the pharmacologic reward from cigarette smoking

Answer 39

Molecular target: 5-HT2A in the CORTEX Symptoms: changes in sensation, illusions, hallucinations, creation of fantasies or living nightmares (called mind-beinding drugs) Treatment: For non-psychotic agitation- antianxiety drugs (diazepam) For severe agitation - use antipsychotic drugs

2-18 Drug Tolerance / Abuse / Dependence Flashcards

(63 cards)