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27 Cards in this Set

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when standard drug dose, if repeatedly administred progressively produce less effect, and increasing dose is required.
Cross tolerance
tolerance to the effects of other opiates that act on the same type of opiate receptors (ie mu receptor).
Physical dependance
condition where normal physiological function requires continued presence of the drug- in its absence, causes withdrawal or abstinence syndrome.
when another opiate can supress withdrawal of an opiate ie. using methadone to supress heroin withdrawals.
overall PATTERN of drug use-- compulsive use, securing supply, and tendency to replase after withdrawal. Addiction may be present in individuals showing NO SIGNS of withdrawal or dependance on opiates.
The very first dose of an opiate experience
in healthy individuals, it's averseive; nausea, emesis etc.
If it's so nasty, why do people end up becoming addicted?
social pressure, the 'rush', subsequent mood elevation with sedation (escaping external demands for upto 4 hours). It also fills psychological need (feeling normal)
Consequence of opiate addiction
no real physiologic consequence only if opiate taken regularly in a sterile fashion (about 2 or more doses per day).
The consequence of opiate addiction in the REAL world?
OD due to impurities, infections, skin ulcers, endocarditis, emboli, hepatitis, psych and social conseq.
How's withdrawal precipitated?
use opiate antagonists such as Naloxone
How's withdrawal suppressed?
give more heroin or another opiate.
how to make dx of drug-dependant state?
give small dose of Naloxone, which would then precipitate brief, mild withdrawal syndrome.
What are the withdrawal characteristics
6-12 hrs: lacrimation, rhinorrhea, yawning.//

12-24 hrs: restless sleep//

16-96 hrs: dilated pupils, gooseflesh, muscle spasm, CNS stimulation (EJACULATION or ORGASM), dehydration, ketosis.
Are withdrawals fatal?
No, unless pt previously ill or something. Max severity at 48-72 hrs. //

cravings will continue for months to years.//
Withdrawal: Time course vs. length of drug action
long last opiate (methadone) will give long lasting (10-14 days) BUT mild withdrawal.//

Meperidine, short-acting will have more intense sx first 24 hrs but decline within 4-5 days.//
What's Conditioned withdrawal syndrome?
return to an environment in which drugs have previously been used may induce intense cravings.
Opiate withdrawals in newborn
If mother heroin-addict-- sx less severe.//

If mother was on methadone, then sx more severe.//

Tx: put on opiates and gradualy tapper off to smaller doses progressively.//
What's the Mech for Tolerance to opiates?
the neurons become LESS SENSITIVE but NO DOWNREGULATION of receptors. Also, alterations in expression of some neural genes.//
What's the Mech of dependance?
neurons adapt to function normally despite presence of drug e.g by increasing enzymes inhibited by drug.
Mech of withdrawal?
the adaptations to drugs decay slower than opiate excretion, therefore resulting in excitability.
Mech of addiction and 'reward'?
Opiates reduces release of GABA, causing disinhibtion of DA and enhanced DA release in Nucleus accumbens, and ventral tegmental area.//

Noloxone blocks effects of opiate drugs in nuc. accumbens.//
Tx of addiction with Methadone
spreads withdrawal over 3-6 weeks, intense cravings report but other sx mild. INPATIENT use only.
Tx of addiction with Clonidine
alpha-2 R agonist, acts centrally, reduces severity of withdrawals.//

decrease NE firing, which otherwise increases during withdrawal, in Locus Ceruleus.// Not useful in heavy drug addicts. Side effects dry mouth, sedation and euphoria.//
Methadone maintainance?
long half-life, give complete cross-tolerance, daily oral administration. INPATIENT only.
Buprenorphine maintainanace
a partial agonist, high rate of retention. Given orally with naloxone (poorly absorbed antagonist), so buprenorphine produces mild agonist effects. //

approved for OUTPATIENT settings.//
How about using antagonists to treat?
They cause brief but severe withdrawal, therefore retention rate is low. NOT recommended.
Px for heroin addicts?
go through several cycles of addiction. 80% relapse in 6 mo to a year.//