FOBS Exam II Pharm Flashcards
1
Q
Drugs of ADHD
A
Methylphenidate Amphetamines Lys-dexamphetamine Pemoline Atomoxetine
2
Q
Amphetamines are CNS Stimulants that act to
How are they diff in adults and children?
A
enhance DA in the synapse, enhanced NE neurotransmission in the CNS
Adults - euphoria, insomnia, appetite suppression, and shift to paranoia
Children - calm hyperactive behavior
3
Q
Mechanism of amphetamines
A
run the DA re uptake transporter (DAT) in reverse (synaptic concentration of DA are increased)
reverse the action of the re-uptake transporter at catecholamine synapses (NE and DA levels are elevated)
4
Q
children with ADHD have a DAT that runs
A
in reverse - extrudes DA (ADHD sx)
so amphetamines cause them to start fxning to take up DA (slowing behavior)
5
Q
Methylphenidate mechanism
A
facilitation of release of central DA and NE
mechanism in ADHD is unknown though
6
Q
Methylphenidate metabolism
A
hepatic metabolism
2.5 h 1/2 life
dosing in the morning and during school hours
penetration to CNS is slower compared with cocaine or amphetamine (lower abuse potential)
7
Q
Methylphenidate toxicity and contraindications (CI)
A
insomnia
anorexia
weight loss and growth retardation (long term therapy)
CI in HTN, glaucoma, anxiety, seizure disorder
8
Q
Methylphenidate XL
A
Extended release
effects last 12-14 hours (dont need to give during school hours)
9
Q
Methylphenidate transdermal patch
A
Slow onset - delayed 1 hr, good for kids who can’t swallow pills
Approximately 8 - 10 hr effect
Take off patch!!
10
Q
Amphetamine Combinations
A
d-amphetamine saccharate
amphetamine aspartate
amphetamine sulfate
d-amphetamine sulfate
different salts contribute to more sustained effects because the salts have diff rates of going into solution in GI tract
11
Q
Most likely to be abused ADHD formulation?
A
Amphetamine combination (adderall)
12
Q
Lys-dexamfetamine
Children or adults?
A
Both children and adults - decreased the abuse potential of the d-amphetamine (bound to lysine that has to be split off in liver)
13
Q
amphetamine side effects
A
insomnia, weight loss, emotional lability (adults - elated/out going to angry/withdrawn, emotions not seen so much in children)
High doses in adults can cause paranoia
14
Q
Major problem with prescribing amphetamines
A
high abuse potential
Schedule II agents
15
Q
Pemoline
Duration of action
Toxicity
Abuse
A
Equal to methylphenidate in effectiveness
Long duration of action
HEPATOTOXICITY
No abuse potential
16
Q
Atomoxetine
Duration of action
Toxicity
Abuse
A
NE selective reuptake inhibitor
Non-stimulant, long acting
Anticholinergic effects - BPH males are not good candidates
Low abuse potential
17
Q
BZD Agonists
A
Diazepam Alprazolam Lorazepam Oxazepam Flurazepam Triazolam Estazolam Temazepam
18
Q
BZD antagonist
A
Flumazenil
19
Q
BZD-1 Selective Binding Drugs
A
Eszopicolone
Zolpidem
Zaleplon
20
Q
Sedative definition
A
diminish awareness
cause drowsiness
diminish motor activity
21
Q
Hypnotic definition
A
promotes sleep and inhibits wakefulness
22
Q
GABAa receptor complex effected by what anxiolytics/sedative-hypnotics
A
BZD
Barbiturates
Ethanol
23
Q
Alpha unit binds
Alpha/beta junction binds
Gamma unit used for
A
GABA
BZD
Gamma unit present for BZD to modulate GABA
24
Q
When GABA binds the channel opens to release
A
Cl- ions
Increased Cl- conductance inhibits neural firing
Decrease Cl- conductance excites neurons (seizures –> why local anestheics can cause seizures because they effect the small unmyelinated fibers first which GABA neurons are small unmyelinated)
25
BZD as an hypnotic
Problem with combining with other hypnotics?
Dependence?
```
Efficacious hypnotic with fast onset
SAFE by themselves
When combined with sedative-hypnotics such as etoh or barb, lethality is enhanced
Dependence is a serious problem
Long half lives = hangover
```
26
BZD Overdose
Usually not a problem
| If mixed with EtOH or opioids --> severe respiratory depression
27
Diazepam
Actions
Half life
anxiolytic, hypnotic, muscle relaxant, pre-anesthetic
blocks convulsions in EtOH or BZD withdrawal
Terminates status epilepticus (second to lorazepam which is more water soluble)
Long half life = 50+ hrs
28
Alprazolam
Actions
Side effects
Anxiolytic, hypnotic
Intermediate acting
Early morning awakening, tolerance/dependence if over-used, less sedative than other BZD
29
Lorazepam
Anxiolytic and hypnotic
| DOC for status epilipticus - better water solubility
30
Oxazepam
| Beneficial for people w/ this dz?
Anxiolytic and for sleep induction
Live dz patients and elderly because better pharmacokinetics (changes in Phase 1 metabolism)
Also seen in Temazpeam and Lorazepam
31
Drug interactions with BZDs
Additive: EtOH, BZDs, opioids, antipsychotics, TcA, antihistamines
32
BZD Abstinence Syndrome (withdrawal signs and sx)
Signs: tremor, seizures
Sx: anxiety, insomnia, nausea, malaise
33
BZD tolerance
More tolerance with sedative than anxiolytic
Many pts escalate the dose to treat anxiety or insomnia
Higher the dose, more frequent the dose, longer the dose is taken = greater the tolerance
Greater the physical dependence = nastier the withdrawal syndrome
34
BZD dependence problem with anxiety
Initial anxiety returns during withdrawal
Additional anxiety occurs because of withdrawal
= intolerable anxiety
Sx occur BEFORE signs of withdrawal
35
BZD Dependence
Cross dependence with other sedative hypnotics - EtOH and barbs
"Dependence of the sedative-hypnotic type"
Limit the # of pills in a prescription and counsel the pt
36
Shorter elimination 1/2 life drugs give what kind of s/sx of withdrawal
Nastier
| Longer are less severe but more protracted (consider giving a long acting BZD if withdrawal s/sx seem to be intolerable)
37
Two problems with insomnia
getting to sleep
| staying to sleep
38
BZD as sedative-hypnotics
Problem with long, short, intermediate acting?
Problem with all BZDs?
Effective
Hangover with long-acting BZDs
Rebound insomnia and anxiety in short acting
Early morning awakening in short/intermediate acting
Tolerance/dependence/withdrawal
39
Triazolam
1/2 life
SE
Short half life = 3-4 hours
No hangover
SE: rebound insomnia and other withdrawal signs with continued use (some even with 1 dose), amnesia, tolerance
40
```
Zolpidem
Binds what?
As efficacious as BZD?
1/2 life?
Abuse?
Rebound insomnia?
```
Binds a subset of BZD receptors (BZD1) - not a BZD!!
Nearly as efficacious in producing sleep as a BZD but less anxiolytic, anticonvulsant, muscle relaxant
Short 1/2 life = 3-5 hrs (less hangover)
Abuse/dependence = lower than BZD
No rebound insomnia
41
Eszopiclone
Zolpidem
Zaleplon
All work on what receptor
Selectively to GABA receptors containing the alpha1 subunit (BZD1)
42
Zaleplon
Binds?
Use PRN for what?
Binds BZD1 receptors
Shorter half life than zolpidem = 1 hr
Used for before bedtime or awakening in the middle of the night (4+ hr remaining)
43
Eszopiclone
d-isomer of zopiclone, not a BZD but binds BZD1
44
Melatonin
Hormone from?
Used for?
CI in what?
Pineal gland hormone that regulates sleep/wake cycle
Useful for sleep problems related to jet lag, changing day/night working hours
Variable dose - can get OTC, no dependence problems
Depression is Contraindicated
45
Ramelteon
Binds?
Abuse?
Withdrawal?
Binds melatonin receptors (MT1 and MT2)
No dependence of abuse liability
No rebound insomnia or withdrawal
46
Can't use Ramelteon with
Fluvoxamine - bc it binds CYP1A2 inhibiting its metabolism
47
Caution in administering any hypnotic to a pt with a hx of
Depression
48
Barbiturates
Pentobarbital
Secobarbital
Phenobarbital
49
Barbiturates Therapeutic Index
Poor
| Phenobarbital for seizure control and the other two are supervised (hospital) as sleep agents (seco/pentobarbital)
50
BZD + Barbiturates
Profound CNS depression, anesthesia, coma
Respiratory depression
Abuse potential
51
BZD vs Barbiturates
Both facilitate GABA but neither bind GABA site directly
Barb directly increase Cl- flux at high doses
No dose of BZD ever directly affects Cl- flux
52
Other OTC Agents that aren't melatonin as hypnotic
Antihistamine and block muscarinic receptors - limited dose range (if too high can be more sedative)
Less efficacious and tolerance occurs more rapidly
53
Drugs for Control of Appetite
```
Low-efficacy CNS stimulants
Topiramate
Phetermine + Topirmate
Fluoxetine
Orlistat
Fenfluramine
```
54
Weight-control programs
EXERCISE
Restriction of energy intake (anorexiant medication)
Behavioral modification
55
Criteria for anorexiant medication
BMI > or equal to 30
OR
BMI > or equal to 27 with HTN, DM, hyperlipidemia
56
Amphetamine anorexiant MOA
Modification of NE and DA neurotransmission (reverse reuptake transporter)
Appetite-control areas of the hypothalamus - NE mechanism, DA in mesolimibic also of interest
57
What amphetamines can't be prescribed for weight loss?
Schedule II agents
58
Therapeutic effects of amphetamine related anorexiants
```
Decrease in appetite
Less interest in food
Less pleasure from eating
Increased satiety with eating
Decrease in total energy intake
```
ONLY LOW EFFICACY CNS STIMULANTS ARE PERMITTED (high efficacy would also give euphoria, and abuse potential)
59
Amphetamine related anorexiants effectiveness:
| Tolerance?
Limited by tolerance (2-3 weeks)
Should discontinue before reaches tolerance
Weight loss then plateau (thereafter, weight gain is likely)
60
Amphetamine related anorexiants precautions
Unusual reactivity to sympathomimetics (amphetamine, epi, isoproternol, phenylephrine, pseudoephedrine, terbutaline)
Dental problems - reduce salivary flow --> exacerbating periodontal disease
61
Amphetamine related anorexiants side effects
```
Insomnia (avoid 4-6 h before bed)
Increased BP
Anxiety
Tremor
Potential for abuse (psychosis, dependence)
```
62
Amphetamine related anorexiants overdose
Arrhythmia, confusion, diarrhea, fever
Assaultive behavior, hallucinations (shift toward paranoid thinking, typically high dose of Schedule II)
Circulatory collapse, coma before DEATH
63
Amphetamine related anorexiants contraindications
```
CVD
Glaucoma
HTN - moderate or severe
Hyperthyroid
Psychosis
Alcoholism
Hx of drug abuse/dependence
```
64
Amphetamine related anorexiants drug interactions
Thyroid hormones
| MOAI
65
Amphetamine related anorexiants names, their classes and specific problems
```
Benzphetamine (class III, CI in preg)
Diethylpropion (class IV, blood dyscrasias)
Phentermine (class IV, long acting/most precscribed)
```
66
Topiramate
Other uses
Untoward effects
Anticonvulsant
| Dizziness, drowsiness, tiredness, attention/memory issues
67
Phentermine + Topiramate
Sympathomimetic + anti-seizure
| Efficacy is good - over 1 yr pts lost weight on a monthly basis
68
Fluoxetine
Other use
How does it help with weight loss?
Tolerance?
SSRI - mood disorders
Appetite reduction - SATIETY
Tolerance develops within days or weeks
69
Orlistat
MOA?
SE?
Tetrahydrolipstatin - bonds and inhibits gastric and pancreatic lipases (prevents hydrolysis of triglycerides to absorable free FA)
Need to supplement fat-soluble nutrients
SE: flatulence, loose stools - esp after high fat meals
70
Herbal/Nutritional supplements that haven't been shown effective
Hydroxy citric acid
Fat binding fiber
Ginkgo, Biloba, vitamin E
71
BZD + Barbiturates
Profound CNS depression, anesthesia, coma
Respiratory depression
Abuse potential
72
BZD vs Barbiturates
Both facilitate GABA but neither bind GABA site directly
Barb directly increase Cl- flux at high doses
No dose of BZD ever directly affects Cl- flux
73
Other OTC Agents that aren't melatonin as hypnotic
Antihistamine and block muscarinic receptors - limited dose range (if too high can be more sedative)
Less efficacious and tolerance occurs more rapidly
74
Drugs for Control of Appetite
```
Low-efficacy CNS stimulants
Topiramate
Phetermine + Topirmate
Fluoxetine
Orlistat
Fenfluramine
```
75
Weight-control programs
EXERCISE
Restriction of energy intake (anorexiant medication)
Behavioral modification
76
Criteria for anorexiant medication
BMI > or equal to 30
OR
BMI > or equal to 27 with HTN, DM, hyperlipidemia
77
Amphetamine anorexiant MOA
Modification of NE and DA neurotransmission (reverse reuptake transporter)
Appetite-control areas of the hypothalamus - NE mechanism, DA in mesolimibic also of interest
78
What amphetamines can't be prescribed for weight loss?
Schedule II agents
79
Therapeutic effects of amphetamine related anorexiants
```
Decrease in appetite
Less interest in food
Less pleasure from eating
Increased satiety with eating
Decrease in total energy intake
```
ONLY LOW EFFICACY CNS STIMULANTS ARE PERMITTED (high efficacy would also give euphoria, and abuse potential)
80
Amphetamine related anorexiants effectiveness:
| Tolerance?
Limited by tolerance (2-3 weeks)
Should discontinue before reaches tolerance
Weight loss then plateau (thereafter, weight gain is likely)
81
Amphetamine related anorexiants precautions
Unusual reactivity to sympathomimetics (amphetamine, epi, isoproternol, phenylephrine, pseudoephedrine, terbutaline)
Dental problems - reduce salivary flow --> exacerbating periodontal disease
82
Amphetamine related anorexiants side effects
```
Insomnia (avoid 4-6 h before bed)
Increased BP
Anxiety
Tremor
Potential for abuse (psychosis, dependence)
```
83
Amphetamine related anorexiants overdose
Arrhythmia, confusion, diarrhea, fever
Assaultive behavior, hallucinations (shift toward paranoid thinking, typically high dose of Schedule II)
Circulatory collapse, coma before DEATH
84
Amphetamine related anorexiants contraindications
```
CVD
Glaucoma
HTN - moderate or severe
Hyperthyroid
Psychosis
Alcoholism
Hx of drug abuse/dependence
```
85
Amphetamine related anorexiants drug interactions
Thyroid hormones
| MOAI
86
Amphetamine related anorexiants names, their classes and specific problems
```
Benzphetamine (class III, CI in preg)
Diethylpropion (class IV, blood dyscrasias)
Phentermine (class IV, long acting/most precscribed)
```
87
Topiramate
Other uses
Untoward effects
Anticonvulsant
| Dizziness, drowsiness, tiredness, attention/memory issues
88
Phentermine + Topiramate
Sympathomimetic + anti-seizure
| Efficacy is good - over 1 yr pts lost weight on a monthly basis
89
Fluoxetine
Other use
How does it help with weight loss?
Tolerance?
SSRI - mood disorders
Appetite reduction - SATIETY
Tolerance develops within days or weeks
90
Orlistat
MOA?
SE?
Tetrahydrolipstatin - bonds and inhibits gastric and pancreatic lipases (prevents hydrolysis of triglycerides to absorable free FA)
Need to supplement fat-soluble nutrients
SE: flatulence, loose stools - esp after high fat meals
91
Herbal/Nutritional supplements that haven't been shown effective
Hydroxy citric acid
Fat binding fiber
Ginkgo, Biloba, vitamin E
92
```
Nicotine epidemiological factors
Education
Social
Mental Illness
Death rate
Dollars
Cancer
```
Lower education - no high school (37%)
Heavy drinkers (12.6%), illicit drugs (13.8%)
Mental illness 50% psych, 70% bipolar, 90% schizo
400,000 premature deaths in US each year
60% health care dollars
30% cancer deaths
93
Nicotine MOA
| 1/2 life
Agonist at the nicotinic subtype of the ACh --> 25% from smoke enters blood and within 15 seconds into the brain
Half life = 2 hrs
DA reward system - binds to cell bodies in the VTA and the dopaminergic terminal of the nucleus accumbens
Stimulates the release of DA and glutamate
94
Smokers are at reduced risk for
Parkinson's
Alzheimer's
Ulcerative colitis
95
Stimulatory effects of nicotine
improved attention, learning, reaction time, problem solving ability
lifts mood, decreases tension, lessens depressive feelings
96
Nicotine in cerebral blood flow
Short term - nicotine exposure increases the CBF without changing cerebral O2 metabolism
Long term - decreases the CBF, skeletal muscle relaxant
97
Nicotine dependence
develops quickly due to VTA dopaminergic activity (same as cocaine and amphetamines)
positive reinforcement is the process by which certain consequences of a response increase --> how nicotine works
98
Acute nicotine intoxication
```
At least one of these:
Insomnia
Bizarre dreams
Lability of mood
Derealization
Interference with personal fxning
AND at least one of these:
Nausea/vomiting
Sweating
Tachycardia
Cardiac arrhythmias
```
99
Nicotine Dependence syndrome
Three or more of for 1 month or w/i 12 month period:
1. a strong desire or sense on compulsion to take substance
2. impaired capacity to control substance taking (termination - longer period of time, onset - persistent desire, level of use - larger amnts)
3. physiological withdrawal when reduced/ceased
4. evidence of tolerance - increased amnts needed
5, preoccupation with substance use
6. persistent substance use despite clear evidence of harmful consequences
100
Nicotine withdrawal
Onset
Sx
Develops with 2 hours and peaks within 24-48
Sx: craving, tension, anxiety, dysphoric mood, irritability, difficulty concentrating, drowsiness, trouble sleeping, decreased HR/BP, increase appetite, weight gain, malaise, decreased motor, increased muscle tension
101
Overdose of Nicotine
60 mg fatal to adults (0.5 mg from common cigarette)
Signs: N/V, salivation, pallor, weakness, ab pain, diarrhea, dizzy, HA, increase BP/HR, tremor, cold sweats, inability to concentrate, confusion, sensory disturb, decreased REM, low birth weight in preg, increase risk of pulm HTN
102
Tx of Nicotine addiction
Abstinence
First line: patch, gum, patch + gum
Second line: nasal spray, inhaler, medications
103
Varenicline
Targets?
Length of tx?
SE?
Target nicotine dependence
Prescribed for 12 weeks
SE: N/V, gas, HA, insomnia, change in behavior, hostility, agitation, depressed mood, suicidal thought/action
104
Bupropion
Smoking cessation drug
Safer than Varenicline
Contraindicated in eating disorder
105
Behavioral therapy for nicotine
```
discover high risk relapse situations
create aversion to smoking
self-monitoring of smoking behavior
competing coping responses
figure out how to perform common daily activities without smoking** and cope with dysphoria/weight gain
```
106
Best tx for nicotine?
Combo of systemic nicotine admin and behavioral counseling (60% sustained abstinence rate)
107
How can smoker women reduce risk of low birth weight babies?
Stop smoking before pregnancy or during first 3 to 4 months to reduce risk
108
One drink =
14 g EtOH
1.5 oz 80 proof whiskey
12 oz beer
4 oz glass of wine
1-2 drinks produces a BEC of 0.025 g/dL or 0.025% or 0.25 mg%
109
EtOH Pharmacokinetics
Peak BEC when?
Absorbed where?
Distribution?
Absorbed rapidly/completely
Peak BEC ~ 30 min (longer with food)
Small intestine primary site
Rapid, passes easily through membranes, distributes total body water, females have smaller volume of distribution = higher BEC
110
EtOH metabolism and elimination
Small, predictable amounts excreted through lungs/urine/sweat (breathalyzer)
Metabolized by oxidation in liver
ZERO ORDER KINETICS
111
Zero Order Metabolism of EtOH
Independent of concentration
Varies slightly with body weight/liver weight
7 to 10 g/hr
112
Primary route of EtOH metabolism
EtOH --> acetaldhyde by Alcohol dehydrogenase that requires an NAD+ to NADH
(90 to 98% ingested EtOH)
Cytosol
113
What may be responsible for HA in hangover?
Acetaldehyde
114
Secondary route of EtOH metabolism
Ethanol --> Acetaldhyde by MEOS using NADP+ to NADPH
Microsomal EtOH Oxidizing System
Microsomes of smooth ER
When EtOH is high and NAD is inadequate
115
Acetaldhyde metabolism
Acetaldhyde --> acetate via aldehyde dehydrogenase with NAD
Cytosol and mitochondria
Acetate --> acetyl CoA --> TCA
Chronic alcoholics have too much acetate --> acetoacetate --> ketosis
116
EtOH induced metabolic disorders
Reduced gluconeogensis
Hypoglycemia
Ketoacidosis
Increase triglyceride synthesis from free FA
bc excess NADH and NADPH
117
Acute EtOH of liver
Increased O2 utilization
Decreased gluconeogensis
Increased lactate production
Decreased oxidation of FA - increased fat accumulation (blocking blood flow in the liver causing cirrhosis)
118
EtOH effects on Ion channels
Chloride - GABA gated is facilitated
| Calcium - Glutamate gated is inhibited (NMDA)
119
Acute EtOH on cardiovascular
Vasodilation - hypothermia producing effects of EtOH (smooth muscle relaxation by acetaldhyde, depression of vasomotor system in CNS)
Depression of myocardial contractility
120
Acute EtOH on endocrine
Diuresis - inhibition of antidiuretic hormone release (all ADH release is prevented)
121
BEC = 50 - 100 sx
Sedation
Subjective "high"
Increased time to react to stimuli
2-4 quick drinks
122
BEC = 100 - 200 sx
Impaired motor fxn
Slurred speech
Ataxia
123
BEC = 200 - 300 sx
Emesis
| Stupor
124
BEC = 300 - 400 sx
Coma
125
BEC > 500 sx
Respiratory depression
| Death
126
Acute tolerance to EtOH
Intoxication more pronounced when BEC is rising than when falling
BEC rising --> brain DA in mesolimbic released --> stimulating
BEC falling --> drowsiness
127
Acute/Chronic ETOH on CNS
Blackouts - anterograde amnesia
Fragmentation of sleep patterns - diminish REM sleep early
Relaxes muscles in pharynx - snoring, sleep apnea
128
Management of acute alcohol intox
Prevent respiratory depression
Prevent aspiration of vomitus
GIVE THIAMINE before glucose (avoid Wernicke's encephalopathy)
Glucose for hypoglycemia/ketosis
May need to tx electrolyte/phosphate levels
129
How do you get Wernicke's in acute alcohol intox?
Increased NADH favors the conversion of pyruvate to L-lactate instead of to glucose and if thiamine deficient and only given glucose --> lacticacidemia
130
Chronic EtOH signs
Wernicke-Korsakoff, neuropathy, cerebeller degen
Myopathy
Hyperlipidemia/uricemia, anemia, thrombocytopenia
Isolated wrist drop
Gastritis, pancreatitis, malabsorption, malnutrition
131
Chronic EtOH liver disease
Steatosis - reversible - 90%
Hepatits/fibrosis - 40%
Cirrhosis/failure - 15-30% (fibrous nodules and loss of normal structure of the liver tissue w/ fxnal decline; women > men; hep B/C to make worse)
132
Chronic EtOH GI signs
pancreatitis - 3x higher than general public
gastritis
reversible SI injury - diarrhea, weigh loss, vit deficiencies
blood & plasma protein loss
133
Chronic EtOH & cancer
Cancer - 10x increase carcinoma
134
Chronic EtOH & heart
Cardio - dose/dependent HTN (~15% of all HTN is related to heavy alcohol consumption),
cardiomyopathy (dilated, ventricular hypertrophy/fibrosis)
arrhythmias
increased HDL cholesterol
135
Chronic EtOH tolerance
Adaptive changes such that proteins, cells, tissues, organs, systems and individuals are less affected by EtOH
Increased MEOS
Attenuation of drug effect due to learning to cope with intoxication
Cross tolerance with other sedative-hypnotics
136
Chronic EtOH dependence
Ethanol withdrawal syndrome
| Craving and desire to avoid withdrawal
137
EtOH withdrawal syndrome
Amount, rate and duration of alcohol consumption can affect severity
Repeated withdrawals - increase probability of more severe withdrawal
Sx: hyperexcitability, convulsions, toxic psychosis, delirium tremens
138
Delirium Tremens
Relatively rare, but life threatening
Mental confusion with fluctating levels of consciousness
Tremor
Agitation
Autonomic over-activity (increase BP/P/R)
139
Management of EtOH Withdrawal
```
Thiamine
Glucose
Prevent seizures - diazepam/BZD
K, Mg, Phos
Psychosocial therapy, pharm
```
BZD substitute for EtOH with tapering (long acting BZD like diazepam, but use oxazepam/lorazepam for liver dz)
140
When DT's occur can you give BZD?
Little impact
141
Wernicke-Korsakoff
Wernicke's: confusional state associated with alcoholic thiamine deficiency - tx with thiamine
Korsakoff's: long lasting memory impairment (confabulations)
142
Fetal Alcohol Syndrome
```
Epicanthal folds at corner of eye
Low nasal bridge
Short nose
Indistinct philtrum
Small head
Small eye opening
Small midface
Thin upper lip
Retarded body growth
Poor coordination
Minor joint anomalies
Heart/kidney defects
Greatest preventable form of MR
```
143
Best treatment of alcoholism
AA
144
Genetics of alcoholism
higher concordance for monozygotic
| four fold increase risk in children of alcoholics
145
Alcoholic Labs
Increase MCB
| Increase liver enzymes (GGT and CDT)
146
Naltrexone
Opioid antagonist (mu)
Reduces CRAVINGS
Can't use in impaired liver or opioid pts
147
Acamprosate
Treating abstinent alcoholics
Reduces CRAVING
Blocks NMDA and activates GABAa
Combo with naltrexone or conseling/psychosocial
148
Disulfiram
Aversion therapy
Blocks aldehyde dehydrogenase
Acetaldehyde syndrome - N/V, flushing, HA, sweating, confusion
149
EtOH as a therapeutic in what?
MeOH and Ethylene Glycol poisoning
Used with hemodialysis, emesis, gastric lavage, correction of acidosis, supportive care
Higher affinity for alcohol dehydrogenase - inhibit formation of toxic aldehydes
150
Fomepizole
Inhibit the action of alcohol dehydrogenase to reduce synthesis and accumlation of toxic aldehydes
MeOH and ethylene glycol poisoning
151
Psychostimulants
Cocaine
Amphetamines
Nicotine
152
Hallucinogens
LSD, LSD-like
Phencyclidine
Ketamine
MDMA
153
Most drugs of abuse increase ____ in ____
DA in nucleus accumbens
154
Targets of drug abuse in the brain
Reward pathway
VTA, nucleus accumbens, prefrontal cortex
VTA connected to both - VTA release DA to NA and prefrontal cortex --> rewarding stimulus
155
Differences in route of admin
Oral - slow absorption for most, ethanol is rapid
Sublingual: more rapid than oral, bittera alkaloid taste deters
Nasal: readily absorbed
Inhaled: allows drug to reach large absorbing surface - high concentration to brain quickly
IV: most direct route
156
Termination of reinforcing effect is associated with
declining plasma concentration
abused drugs tend to have short t1/2 lives
continued drug taking to achieve reinforcing may lead to accum in plasma at toxic level
157
Pharmacokinetic Tolerance
Changes in distribution or metabolism of a drug after repeated admin --> diminished concentration of drug at site of action
158
Pharmacodynamic Tolerance
Adaptive changes in target tissue occur with repeated use so diminished reponse to the same concentration of drug (reduced receptor density, uncoupling of receptors to signal transduction, compensatory changes in systems mediating opposing effects)
159
Learned Tolerance
Behavioral: skills developed through experience with drug
| Conditioned tolerance: pairing of drug admin with a specific environmental cues related to drug taking
160
Acute tolerance
rapid tolerance developing w/ repeated use on single occasion (cocaine)
161
Cross tolerance
Tolerance conferred upon one or more other drugs as a result of repeated use of a given drug (drugs in same structural/mechanistic category)
162
Sensitization
increase in response to a drug after repeated admin
163
Cocaine
| MOA
Reinforcing correlated with blocking DA transporter; also binds NE and 5HT transporters
Also local anesthetic action - convulsion effect in OD
164
Cocaine
| Targets
Reward pathway: VTA - NA (mesolimbic/cortical DA pathway)
Arousal: NE - Locus Ceruleus, dorsal bundle
Autonomic: NE in periphery (BP, arrhythmia)
165
Cocaine
Sources
Forms
Coca plant Erythroxylon coca (peru, bolivia, coloumbia, argentina, brazil, ecuador)
Chewing leaf or powder (snorting, oral, IV, smoked = crack - less effect)
166
Cocaine
| Pharmocokinetics
1/2 life = 50 min
Toxicity by local anesthetic action
Fatality related to plasma concentration from binge abuse to maintain high
167
Cocaine
Effects
Acute
```
Euphoria
Arousal
Sense of psychic/physical well being
Self confidence
Improved vigilance/alertness
Increase HR/BP
Decrease appetite
Delays ejaculation
```
168
Cocaine
Effects
Chronic
```
Dysphoria
Stereotyped behavior
Anxiety
Sexual dysfxn: impotence
Hallucination: objects in periphery, voices, sensations of bugs crawling under skin
Paranoia
Hyperreflexia
Convulsions, coma, CV collapse
```
169
Cocaine
| Withdrawal
Dysphoria, depressed mood
Fatigue
Craving
Bradycardia
170
Cocaine
| Toxicity
Fatality MC with IV or smoking
Arrhythmias (NE/E at heart), seizures, coma, CV collapse
MC due to binge usage over several hours (toxic plasma levels)
171
Cocaine
| Interactions
Opioids
| Alcohol - cocaethylene --> long 1/2 life, blocks DA transporter
172
Cocaine
| Tolerance
Occurs to euphoria during a run of use but not much carryover tolerance
Don't really escalate dose across sessions
173
Amphetamine
| MOA
Reinforcing effects correlates best with presynaptic release of DA (reuptake transporter in reverse)
174
Amphetamine
| Neural Targets
Reward pathway: VTA --> NA (mesolimbic/cortical DA pathway)
Arousal systems (NE pathway --> Locus ceruleus/dorsal bundle)
Autonomic: not as profound as cocaine
175
Amphetamine
Effects
Acute
```
Alertness/anti-fatigue
Euphoria
Anorexia
Emotionality
Toxic psychosis with chronic use
```
176
Amphetamine
| Toxicity
Low acute toxicity
Paranoid psychosis and violence in high dose/prolonged used
Sympathetic arousal
177
Amphetamine
| Drugs
d-Amphetamine
methamphetamine - ice is smoked
methylphendiate - ritalin
phenmetrazine
178
Military uses what for anti-fatigue?
Amphetamine
179
Tx for Narcolepsy
Amphetamine but low abuse potential ones - modafanil and armodafanil
180
Nicotine MOA/targets
Agonist at CNS/peripheral nicotinic sites
Activate VTA --> NA with DA pathway (less so than amphet/cocaine)
Onset with 7 seconds --> 10 puffs/cig
Stim and depressant --> more alert and less tension
181
Indoleamien like hallucinogen
LSD (lysergic acid diethylamide)
DMT (dimethyltryptamine)
Psilocybin (mushrooms)
182
Phenethylamine like hallucinogen
DOM (dimethoxymethylamphetamine)
MDMA derivatives
Mescaline
183
MDA/MDMA
Methamphetamine analog
Modest stimulant/hallucinogen
Initial sedative/dysphoria
184
Phencyclidine
| MOA
PCP, angel dust, ozone, rocket fuel
Non-competitive blocker of NMDA receptors
Smoking, snorting, oral
Psychotomimetic effects with profound tolerance
12-24 hr 1/2 life
185
Phencyclidine
| Effects
Euphoria
Staggering
Disorientation
Paresthesia
Nystagmus
Slurred speech
Distortion of body image
Strength/power/invulernability/anger/rage
Depression/paranoia/hostility
Moderate dose - tachy, increase BP, mydriasis, xerostomia
High dose - analgesia, anesthsia, decreased BP/R, horizontal/vertical nystagmus
186
Phencyclidine
| OD
Anxiety, agitation, aggression, hallucination
Dysphoria, catatonia, muscle rigidity, convulsion
Tachy, sweating, salivation, lacrimation, HTN crisis
187
Ketamine
| MOA
Special K, vitamine K, cat valium
Dissociative anesthetic, non-competitive blocker of NMDA receptor
Power/liquid - snorted, smoked
188
Ketamine
| Effects
Disorientation
Sensory illusions
Hallucinations
189
Marijuana
| MOA
Dope, pot, grass, reefer, herb, ganja
Binding to cannabinoid receptors
Smoked, food, tea
190
Marijuana
| Uses
```
delta-9-THC and dronabinol for
Glaucoma
Reduce N/V in chemo
Anorexia - weight loss in AIDS
Recreational
```
191
Marijuana
| Pharmacokinetics
```
Rapid absorption following inhalation
Euphoria after 10-30 min for 3-4 hours
Accum in fatty tissue
Active and inactive metabolites
10-15% urinary excretion - up to 30 days
```
192
Marijuana
| Acute Effects
```
Increased pulse
Decrease exercise tolerance
Reddening on conjunctiva
Euphoria/relaxation
Impaired memory/motor coord
Distorted time sense, hunger, dizzy
```
193
Marijuana
| Chronic Effects
```
Bronchial - irritation, impaired fxn, cancer
Aggravation of angia
Ortho hypoTN
Decrease testosterone
Diminished intellect
Amotivational
```
194
Marijuana
| Dependence
Tolerance reported
| Withdrawal: anorexia, N/V, diarrhea, irritability, restlessness, insomnia (after sudden stopping of prolonged use)
195
Marijuana
| Overdose
Euphoria, time space distortion, tachycardia, fever
Psychosis (hallucinations, depersonalization)
tx with haldol/diazepam for agitation and propranolol for CV
196
Inhalants
glue, gasoline, nail polish
damage to neurons, kidney, liver
excitation followed by drowsiness, disinhibition, staggering, agitation
197
Nitrates/Nitrites
Systemic vasodilators (amyl nitrate, butyl nitrite)
Abuse associated with enhancedment of sexual sensations
Toxicity: HA, peripheral pooling of blood, decrease myocardial flow
198
GHB
alcohol like effects, anabolic steroid like effects, aphrodisiac
synergistic interaction with alcohol - coma like sedation (date rape)
199
Flunitrazepam
Rapid onset BZD
Sedative-hypnotic
Amnestic effect - date rape
