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Flashcards in FOBS Exam II Pharm Deck (199):
1

Drugs of ADHD

Methylphenidate
Amphetamines
Lys-dexamphetamine
Pemoline
Atomoxetine

2

Amphetamines are CNS Stimulants that act to
How are they diff in adults and children?

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

Mechanism of amphetamines

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

children with ADHD have a DAT that runs

in reverse - extrudes DA (ADHD sx)
so amphetamines cause them to start fxning to take up DA (slowing behavior)

5

Methylphenidate mechanism

facilitation of release of central DA and NE
mechanism in ADHD is unknown though

6

Methylphenidate metabolism

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

Methylphenidate toxicity and contraindications (CI)

insomnia
anorexia
weight loss and growth retardation (long term therapy)
CI in HTN, glaucoma, anxiety, seizure disorder

8

Methylphenidate XL

Extended release
effects last 12-14 hours (dont need to give during school hours)

9

Methylphenidate transdermal patch

Slow onset - delayed 1 hr, good for kids who can't swallow pills
Approximately 8 - 10 hr effect
Take off patch!!

10

Amphetamine Combinations

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

Most likely to be abused ADHD formulation?

Amphetamine combination (adderall)

12

Lys-dexamfetamine
Children or adults?

Both children and adults - decreased the abuse potential of the d-amphetamine (bound to lysine that has to be split off in liver)

13

amphetamine side effects

insomnia, weight loss, emotional lability (adults - elated/out going to angry/withdrawn, emotions not seen so much in children)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

Major problem with prescribing amphetamines

high abuse potential
Schedule II agents

15

Pemoline
Duration of action
Toxicity
Abuse

Equal to methylphenidate in effectiveness
Long duration of action
HEPATOTOXICITY
No abuse potential

16

Atomoxetine
Duration of action
Toxicity
Abuse

NE selective reuptake inhibitor
Non-stimulant, long acting
Anticholinergic effects - BPH males are not good candidates
Low abuse potential

17

BZD Agonists

Diazepam
Alprazolam
Lorazepam
Oxazepam
Flurazepam
Triazolam
Estazolam
Temazepam

18

BZD antagonist

Flumazenil

19

BZD-1 Selective Binding Drugs

Eszopicolone
Zolpidem
Zaleplon

20

Sedative definition

diminish awareness
cause drowsiness
diminish motor activity

21

Hypnotic definition

promotes sleep and inhibits wakefulness

22

GABAa receptor complex effected by what anxiolytics/sedative-hypnotics

BZD
Barbiturates
Ethanol

23

Alpha unit binds
Alpha/beta junction binds
Gamma unit used for

GABA
BZD
Gamma unit present for BZD to modulate GABA

24

When GABA binds the channel opens to release

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