Flashcards in Pharm- 18 Deck (57)
What is substance dependence/addiction?
maladaptive use leading to significant impairment or distress
Symptoms: loss of control, salience to the behavioral repertoire, and neuroadaptation
Fundamental element: drug-seeking
What is tolerance?
decreased effect of a drug that develops w/ continued use; the dose-response curve shifts to the right as larger doses are needed to produce the same response
What is acquired tolerance?
epeated administration of a drug shifts the dose-response curve of the drug to the right, therefore a larger dose of the drug is required to produce the same effect
What is innate tolerance?
preexisting interindividual variations in sensitivity to the drug ; exist prior to the first administration of the drug
What pharmacokinetic properties of tolerance result from the increased capacity to metabolize or excrete the drug?
Results in a lower concentration of drug at its site of action for any given dose
What are the pharmacodynamic causes of tolerance?
caused by neuronal adaptations resulting in reduced response to the same concentration of drug at its site of action in the NS.
What are the short-term exposure dynamics of tolerance?
induces neuroadaptive changes in NT release and clearance from the synapse, ↓ in the number of NT receptors, altered conductance of ion channels, or modified signal transduction
What are the long-term exposure dynamics of tolerance?
euroadaptive changes in the expression of genes of relevant to the pharmacologic action of the drug
What is dependence?
defined only indirectly by: 1) tolerance, 2) emergence of a withdrawal syndrome upon drug discontinuation or administration of a specific antagonist, 3) drug “craving”, 4) drug-seeking behavior manifested as a result of conditioned stimuli after withdrawal has abated
What is physical dependence?
initial symptoms experienced after withdrawal; results from the same mechanisms that produce tolerance
What is psychological dependence?
resetting of the reward system of the brain as a result of repeated drug use
What is dependence syndrome?
need for the drug to be present in the brain to maintain “near-normal” functioning
What happens in acute withdrawl syndrome?
occurs when the drug eliminated from the body therefore it no longer occupies its site of action as a result the adaptations that produced dependence are expressed; these symptoms last until the system re-quilibrates to the absence of the drug (days)
What happens in protracted withdrawl syndrome?
characterized by a craving for the drug and may emerge and continue for forever; intense preoccupation with obtaining the drug
Medial forebrain bundle and ventral tegmental area (VTA) in the midbrain are the source for what?
pleasure/reward centers ;-)
What is the fxn of the nucleus accumbens?
crucial for the brain reward pathway
Reinforces motivated behavior and facilitates learning and memory via links to the hippocampus, amygdala, and prefrontal cortex
What is the main NT for the reward pathway of the brain?
What class of drug does oxycodone and heroin belong to?
What happens in cross-dependence?
multiple inputs into brain reward circuits underline the potential for co-occurrence of addiction to opioids and to other pharmacologically disparate drugs of abuse
Opioids- mech of action
Interacts w/ Brain Reward System via μ- opioid receptor: 1) Venral tegmental area- disable GABAergic interneurons; these interneurons naturally inhibit dopaminergic; disinhibit dopaminergic neurons in the VTA 2) Localized in the Nac; inhibit GABAergic neurons that project back tot he VTA (inhibitory feeback loop)
Euphoria, followed by sedation, respiratory depression (heroin is hydrophobic --> quickly cross BBB --> quicker high --> more addictive)
Opioids- withdrawl Sx
High potential for withdrawal symptoms upon discontinuation of an opioid therfore pt needs to be tapered off
How does buprenorphine Tx opioid detox?
partial agonist; binds to and modulates μ-opioid receptor- mediated reward circuits --> diminishes cravings for opioids
How does naloxoneTx opioid detox?
competitively block binding of opioids to the μ- opioid receptor (Naloxone [opioid overdose; rapid reversal of opioid activity] & Naltrexone [opioid dependence])
How does methadone Tx opioid detox?
synthetic opioid agonist that binds and activates the μ-opioid receptor; opioid detox and severe pain
The drugs triazolam, Phenobarbital, diazepam, clonazepam belong to which class?
Benzos/barbs- abuse potential
All sedative-hypnotics are can cause dependence; however risk of abuse is decreased if they are used cautiously in a time-limited fashion; rarely cause death due to overdose when used alone [combine with EtOH --> death]
Benzos/barbs- mech of action
Increase efficiency of GABAergic (GABAA receptors) pathways; chronic use lead to down-regulation of these pathways by neuroadaptation --> leaves the brain "uninhibited" --> increasing the possiblity of seizures and derlirium [actions of barbituates are more widespread than those of GABAA- specific benzodiazepines]
sedation, respiratory depression, hypnotic; euphoric feelings