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118 Cards in this Set

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Define Tolerance
Altered physiological state, where the same dose of a substance has less effects over time. Dose needs to be increase over time to maintain effects.
Physiological state
Time
Dose
Behavioral Tolerance
Behavior to compensate drug effects eg. take another
Functional Tolerance
Compensatory changes in receptors, effector enzymes, membrane actions of drugs
Why is smoking a good way to take some of these drugs
Rapid effect (onset and elimination)
Can titrate with smoking, take until feel effects and then stop.
With smoking, ctrl it so can't OD. With smoking, can breathe out if too much.
Don't need clean needles, no complication of skin infections
Effect (time)
Adv. over other means
List 4 biological causes of Tolerance
Pharmacokinetic
Main clinical effects of Opioids
Euphoria
Drug used for Heroin detox
Methanol
Name opioid contained in Tylenol
Codeine
Toxidrome for opioid toxicity:
Depressed mental status
Depressed Resp. Status
Mioisis
3
Antidote for opioid toxicity
Naloxene
True or False
Babies born to opioid addicted mothers may have neurological complications that look like Sz. They can die from this
True
How is a pregant heroine addicted mother treated?
Admit!
Methadone
Admit for the sake of the baby.
Symptoms of Heroine withdrawal.
Look like have flu and don't feel well.
Anxiety, fever, lacrimation, rhinorrhea, sweat, insomnia, weak, chills, myalgia, hypertension, yawn.
Rx. Supportive treatment, don't admit.
Dvp 8 -10 hrs after stop drug
Won't kill them
How can treating heroin toxicity lead to withdrawal symptoms?
If addicted and treat with nalaxone, similar immediate stop of drug.
List 4 sedative/hypnotic drugs:
Alcohol
Benzos
Barbituates
Gamma Hydroxy butyrate
What are the symptoms of sedative/ hypnotics toxicity
Depressed mental statuse
Depressed Resp. rate ***
True of False
Withdrawal from sedative/ hypnotics can be life threatening.
True
List withdrawal symptoms from benzodiezapines
Anxiety
Tremors
Nausea
Vomit
SEIZURES
withdrawal over 8-9 days, may be shorter depending on type of drug or how long it was taken for.
What is a Rum fit?
Sz from alchohol withrdawal that occurs in about 1-2hr
Alchohol withdrawal symptoms:
Mild form (1-2 days)
Motor agitation
Anxiety
Insomnia
Sz
Alchohol withdrawal symptoms:
Severe form (3-4 days)
Visual hallucinations
Total disorientation
Tachycardia
hypertension
hyperthermia
Sz
DELIRIUM TREMENS
Treatment for sedative-hypnotic withdrawal.
Supportive - prevent Sz
Replace electrolytes
Replace thiamine (B1)
Admit for severe withdrawal
Drug substitution and
taper with time
What would you give to treat alchohol withdrawal?
Benzos
What would you give to treat GBH withdrawal?
Benzos
Acute ETOH intoxication may cause death directly from?
Respiratory Depression
What system is involved in 90% of metabolism of ETOH to acetaldehyde?
Alchohol dehydrogenase
Name the enzyme that breaks down acetaldehyde:
Aldehyde dehydrogenase
What serum alchohol is legal limit for driving?
80mg/dl
True or False
ETOH is Tissue paralles ETOH in blood
True
What system, other than the dehydrogenase system is involved in ETOH metabolism?
p450 system
Proof = ? alchohol %
1/2
What effect does ETOH have on:
GABA activity
Glutamate activity
Binds GABA receptors and augments GABA activity.
Decreases glutamate activity on its receptors.
CNS depressant
Which of these is a chronic effect of alchohol that is reversible?
Wernicke encephalopathy
Korsakoff pyschosis/syndrome
Wernicke Encephalopathy
As a result of thiamine deficinency
3 main clinical features Wernicke encephalopathy:
Depressed mental status
Wide based gait
Eye findings: Nystagmus & or intranuclear opthalmoplegia - can't track past midline.
clinical features of Korsakoff pyschosis/syndrome
Short-term memory loss
Alchoholics are likely to have Cerebral atrophy. Why is this a concern?
If have head injury, have high risk for subdural hematoma due to stretch of bridging veins.
Also a concern in elderly patients if see change in mental status that can't explain.
Major effects of ETOH on Liver:
Chronic - cirrhosis
Acute: CYP450 induced
Chroni: Liver damage reduces drug metabolizing capacity.
Major effects of ETOH on stomach:
Low ETOH: stimulate acid secretion
Chronic ETOH: Mucosal damage and bleeding
Dose dependent
Major effects of ETOH on cardiovascular system:
Dilates blood vessels by depressing vasomotor center
Lead to heat loss - hypothermia
Chronic use-myocardial damage
Major effects of ETOH on Kidney:
Diuresis - ETOH reduces ADH secretion.
Teratogenic effects due to ETOH:
Fetal alchohol syndrome
CNS impairment
Facial abnormalities
Major effects of ETOH on pancrease:
Pancreatitis
Major effects of ETOH on sexual perfomance:
Low dose - remove inhibitions
High dose - less performance
Dose dependent; for both sexes
List drugs that interact with alchohol:
Drugs that can irritate stomach not used with ETOH - eg. NSAIDS.
ETOH & Acetaminophen - liver damage at high doses
Therapeutic use of ETOH:
Skin anti-infective
Treat Trigeminal neuralgia
Ethylene glycol and ethanol
Treatment of alchoholism
Supportive
Are they breathing? Chance of respiratory depress.
Correct hypoglycemia - usually in pediatrics
Give thiamine
Rule out trauma
Drug substitution & taper
Which of these patients say take less than they do?
Methadone
Alcholic
Alcoholics - in denial
Methadone patients - say they take more, because they want more while in hospital.
What is the MOA of disulfiram?
Blocks aldehyde dehydrogenase. If drink, have build of of acetaldehyde, responsible for miserable side effects.
Antabuse
Name two other susbtances that have disulfiram like activity and should not be used with ETOH
Cochrine muschrooms
Flagil - metronidazole
What are clinical characteristics of methanol toxicity?
Intoxication
Severe acidosis
Blindness
Coma
Death
Windshield washer fluid.
What are clinical characteristics of Ethylene glycol toxicity?
Intoxication
Severe acidosis
Renal failure
Coma
Death
Anti-freeze
Define Sedatives-hypnotics
General depressants of the CNS
Joint definition
Define Sedatives
Reduce daytime anxiety
Decr. excessive excitement
Promote calm state
Define Hypnotics
Produce drowsiness
Promote onset of sleep
Promote maintenance of sleep
What effects do alpha-1 subunits of GABA receptors have?
Sedative and
MEMORY effects ... be mindful of this
What is the difference between Benzos and Barbs?
Benzos a lot safer than Barbs
Benzos level off with increased dose
At high conc, barbs may direcly activate channel, may cause death.
Sedation -- Hypnosis -- Anethesia -- Coma
Name 4 Short acting Benzos
(Safer - not likely to sleep on road in the morning)
Lorazepam 0 - 20hr
Oxazepam 0 - 20hr
Triazolam 2 - 3hr
Alprazolam 12- 15hr
LOT - these are drugs you want to remember, have no active metabolites!!!
Name 3 Long acting acting Benzos
Flurazepam 100hr
Prazepam 100hr
Clorazepate 100hr
BZD side effects
Intoxication
Disinhibition
Impaired judgement, aggressive
Withdrawal - life threatening
How are patients who have been on long-half life BZD for more than a year taken off of BZD?
First 50% withdrawal
Then taper drug by 10% or less per week.
Long half-life up to 6wks, unlikely for withdrawal
List side effects of BZD
Daytime drowsiness
Dizziness
Ataxia
Resp. impairement in patients with COPD
Amnesia, memory impairement
Patients with COPD
Effect of BZD with other sedatives
Coma, increased CNS depression
Interaction btw. antacids and BZD
Decreased absorbption of BZD
List three BZD that are safe to use with Liver problems.
Lorazepam
Oxazepam
Temazepam
Drugs are conjugated and secreted in the urine
What effect does Grape juice, estrogens, Isoniazie, Fluoxetine have on BZD levels?
Also metabolized by the CYP450, therefore Increase BZD levels in blood.
Metabolism
Symptoms of insomnia
Difficulty falling asleep
Difficulty maintaining sleep
Frequent awakenings
Poor quality sleep
Have adequate time to sleep
Characteristics of sleep disorder:
Insomnia and
Distress - daytime sleepiness, mood disturbance, impaired cognition, daytime sleepiness
Epidemeology of insomnia:
What % have chronic or occasional insomnia
30% occasional
10% chronic
Define primary insomnia (15%)
Main problem is insomnia
Define secondary insomnia (85%)
Secondary to medical disorder, pyschiatric and other substance abuse, other sleep disorder eg. restless leg syndrome.
Name 3 behavioral treatments of insomnia
Relaxation training
Sleep restriction therapy (increase sleep efficiency)
Stimulus control therapy
Good sleep hygiene - caffeine has long half life, none after 12pm
Effects of behavioral treatments:
Reduce sleep latency
Reduce wake time after sleep onset
Increase total sleep time
What is the most frequent antihistamine used to treat insomnia?
Benadryl: Diphenhydramine
H1 receptors
Side effects of Benadryl as hypnotic?
Cognitive impairement
Confusion
Sedation
Delirium
Urinary retention in elderly
What are the drugs of choice for insomnia?
Benzodiezapine receptor agonists
List Benzodiezapines that have been approved for the treatment of insomnia:
Estazolam
Quezapam
Temezapam
Triazolam
Flurazepam
List three nonBZD hypnotics that act via alpha subunit of GABA receptor:
Zolpidem - Ambien 2.5hr
Zaleplon - Sonata 1hr
Eszopiclone - Lunesta 6hr
LESS ABUSE POTENTIAL
Which drug would you give to a patient with middle of the night insomnia?
Zaleplon (Sonata)
How is Ambien metabolized?
Liver metabolism
What are the preferred hypnotics?
BZD, Ambien, Sonata
Less risk of fatal OD with threse drugs
Barbs not a drug of choice due to use in suicide attempts.
What's the difference btwn BZD and non-BZD hypnotics?
non-BZD are more selective, bind to omega-1 subtype of GABA receptors whereas BZD bind to all three nonselectively.
Describe the amine hypothesis of depression
Deficiency of amines (NE and Serotonin) in certain parts of the brain leads to depression.
Where in the brain are the cell bodies of Noradrenergic tracts?
Locus Coerulues
Project to:
Caudate
Amygdaloid nucleus
Thalamus
Hypothalamus
Cortex
Where in the brain are the cell bodies of Serotonergic tracts?
Raphe nuclei
Project to limbic system and cortex
List 5 SSRI's
Fluoxetine - prozac
Sertraline - Zoloft
Paroxetine - Paxil
Citalopram - Celexa/ Escitalopram(Lexapro)
Fluvoxamine
Describe the char. of serotonin syndrome seen with SSRI's
Confusion
Fever
Altered consciousness
Myoclonus
MOA of Fluoxetine
Selective inhibition of serotonin reuptake on presynaptic membrane, allowing longer interaction of serotonin with postsynaptic membrane.
Advantage of Sertraline over Fluoxetine
Sertraline has a shorter half life and therefore takes a shorter time to reach steady state. Therefore, it is easier to change patient from sertraline to another drug due to the fact that it gets out of the system faster.
What are the unique char. of paroxetine?
Has anticholnergic effects in addition to SSRI, therefore can relieve anxiety.
Side effects: constipation.
Severe discontinuation syndrome if stopped abruptly
List the therapeutic use of SSRI's
Depression
OCD
Panic disorders
Post traumatic stress disorder
Eating disorder
Generalized anxiety disorder
Premenstrual syndrome
MOA of Tricyclic antidepressants.
They block the active reuptake of NE and serotonin at the presynaptic membrane of NE and serotonin tracts.
What is the current therapeutic use of Tricyclic antidepressants.
Treatment of resistant depression.
Not first line because of high treatment dropout rate due to adverse effects.
List some adverse effects of Tricyclic antidepressants.
Sedation
Anticholinergic (urinary hesitancy)****
Orthostatic hypotension
ECG changes
Weight gain
Headache, tremor, Sz
Obstructive jaundice
Sexual side effects
Class1a anti-arrythmic
Likely to ppt mania
Treatment of poisoning of Tricyclic antidepressants.
Cardiac monitoring
Gastric lavage
Sodium bicarbonate and KCl
Lidocaine or Phenytoin I.V.
Name the only TCA with clinically proven therapeutic drug level.
Noretriptyline
Which TCA interacts with morphine to potentiate morphine analgesic effects.
Amitryptyline
What are the therapeutic of TCA
Depression
Enuresis in childhood
Chronic pain, neuralgias, migraine neuropathy
What effects of TCA's with anti-htn
Reverse of anti-htn action
Which are the original Gold standard drugs that are used to treat depression.
TCA
List two noepinephrine and serotonin reuptake inhibitor (SNRI):
Venlafaxine
Duloxetine
Therapeutic use of venlaxafine
Depression
Generalized anxiety disorder
Social Anxiety Disorder
Panic disorders
PSTD
Premenstrual syndrome
Duloxetine - How is this different between this and venlaxafine.
Diabetic peripheral neuropathy
What is the MOA or Monoamine Oxidase:
Inhibition of intraneuronal monoamine oxidase type A isoenzyme in noradrenergic and serotonergic fiber tracts.
List MAO inhibitors:
Phenelzine - more side effects
Tranylcypromine
Side effects of phenelzine:
*weight gain
*orthostatic hypotension
*hepatotoxicity potential
*anxielytic
Slower onset of action
Sexual dysfunction
Hydrazine derivative
* more than tranlycypromine
Side effects of Tranylcypromine:
sexual dysfunction
Which MAO inhibitors has faster onset of action and some abuse potential
Tranylcypromine - a non-hydrazine
What are the clinical char of an MAOI crisis?
Hypertensive crisis
headache
palpitations
sweating
Chestpain
hemorrhagic stroke
What is the outcome of interaction btw. MAOI and Tyramine foods?
Hypertensive crisis
What is the outcome of interaction btw. MAOI and meperidine?
Convulsions, cardiovascular failure and death
What is the therapuetic use of MAOI's?
Superior for bipolar disorder than TCA
Phobic anxiety states
Migraines
Neurodermatitis
What class of drugs does Buproprion fall under?
Noepinephrine and Dopamin reuptake inhibitor (NDRI)
What is the therapuetic use of Buproprion?
Depression, fewer sexual side effects than SSRI
Smoking cessation
ADHD
Name an antidepressant that is used in smoking cessation
Buproprion
Drug used to treat ADHD
Buproprion
Adverse rxns of Buproprion
Agitation
Dose dependent risk of Sz
headache
nause
Sz
Blurred vission
Advantages of SSRI's over TCA
Do not have quinidine action on heart
Safety margins are higher in OD
No need to measure/follow blood levels
LAck anticholinergic, antihistamine effects
No weight gain
Important dietary restriction for patients on MAOI's
Avoid foods that contain tyramine