Pharm Exam 3

Front 1

cocaine MOA

Back 1

Blocking reuptake of catecholamines and serotonin reuptake; blocks dopamine transporter (DAT) on nerve membrane

Front 2

Cocaine pharmacologic effect

Back 2

1) Initial: euphoria & increased arousal via increase in concentration of dopamine in synaptic cleft in the ventral striatum

2) following the "high" --> netagive feelings and dysphoria (D1 & D2 family receptors sequential)

3) "Crash" = fatigue, prolonged sleep, depression, increased appetite

Front 3

Cocaine therapeutic uses

Back 3

local anesthetic; topical for ear/nose/throat surgery

Front 4

Cocaine Side effects

Back 4

fatal arrhythmias, coronary vasospasm

Front 5

Cocaine clearance

Back 5

Spontaneous hydrolysis, plasma esterases, small hepatic contribution

Front 6

Amphetamine MOA

Back 6

1) Bind to the pre-synaptic membrane and induce release of neurotransmitter

2) Interact with dopamine containing synaptic vesicles, releasing free dopamine into the nerve terminal

3) Bind DAT, causing it to act in reverse and transport free dopamine out of the nerve terminal

Front 7

Amphetamine pharmacologic use

Back 7

delays eating (decreases hunger)

Front 8

Amphetamine therapeutic use

Back 8

Hyperactivity Attention deficit disorder
Narcolepsy
sleep disorders (Use as anorexigenic discontinued due to abuse potential)

Front 9

Amphetamine side effects

Back 9

High abuse potential
Psychosis resembling paranoid schizophrenia
increase BP, reflex bradycardia → risk of arrhythmia
Insomnia, nervousness, anorexia, GI pain, headache

Front 10

Amphetamine clearance

Back 10

primarily excreted unchanged by the kidney (approx
80%).

Front 11

methamphetamine mOA

Back 11

Increases release of DA & NE (& 5HT at high doses) by interacting w/ reuptake transporter to promote reverse transport from cytoplasm to synaptic cleft

Front 12

Methamphetamine clearance

Back 12

primarily excreted unchanged by the kidney (approx
80%).

Front 13

methylphenidate street name

Back 13

ritalin

Front 14

methylphenidate MOA

Back 14

Not well understood, blocks reuptake of dopamine via DAT as well as Norepi transporter

Front 15

METHYLPHENIDATE pharmacalogic effects

Back 15

Methylphenidate has strongest effects in prefrontal and perietal cortex, regions involved in attention and mental focus. These same regions are less active in ADHD individuals during attention tasks, and have even been reported to be shrunken in ADHD brains.

Front 16

Methylphenidate therapeutic fxns

Back 16

ADHD

Narcolepsy

Front 17

Methyphenidate side effects

Back 17

Intermediate abuse potential (greater in adults than kids)
Psychosis resembling paranoid schizophrenia
Insomnia, nervousness, anorexia, GI pain, headache

Front 18

If you block the DAT receptor on mice, do they still like cocaine?

Back 18

Yes! B/c cocaine (and other stimulants) are "dirty" drugs, meaning that they also effect serotonin & norepinephrine in addition to dopamine, so even if you block the DAT, they still have serotonin effects AND norepinephrine effects...

ergo, if you block both DAT & SERT (serotonin transporter) the preference is abolished

Front 19

What is unique about mice w/ NET deletions when given cocaine

Back 19

Mice w/ norepi transporter deletions are supersensitive to the locomotor activating effects of cocaine and amphetamine.

Front 20

phentermine MOA

Back 20

Increases release of DA and NE (& 5HT at high doses)

Front 21

What is the order of "abuse potential" among drugs?

Back 21

cocaine, amphetamine and methamphetamine (highest abuse potential)
>methylphenidate
> sibutramine and phentermine. (lowest)

Front 22

What is phentermine's therapeutic use?

Back 22

appetite suppressants (short term)

Front 23

Phentermine's side effects?

Back 23

Lower abuse potential
Sympathomimetic effects on heart – use caution in pts w/ hx of CV disease

Front 24

sibutramine moa?

Back 24

Blocking reuptake of catecholamines (NE & DA) and serotonin reuptake

Front 25

Sibutramine uses?

Back 25

Long term weight loss via active metabolites of CYP3A4

Front 26

Sibutramine side effects?

Back 26

Lower abuse potential
Sympathomimetic effects on heart – use caution in pts w/ hx of CV disease

Front 27

caffeine MOA

Back 27

competitive antagonism at adenosine receptors

Reduces resting cerebral blood flow

generally disinhibits neuronal activity

Front 28

What is methylxanthine

Back 28

Caffiene

Front 29

Caffeine clinical uses?

Back 29

Used in patients with asthma as a bronchodilator
Use in the US has now been markedly curtailed since the development of beta-agonists, inhaled corticosteroids, and leukotriene antagonists.


--> off label: Sleep apnea in neonatal units accompanied by bradycardia

Front 30

Caffeine pharmalogical effects?

Back 30

CAFFIENE together Binds to receptors and is antagonistic--> prevents ADENOSINE FROM BINDING AND ACTIVATING SIGNAL
--> adenosine REDUCES presynaptic release and stabilize NMDA blockade post synpatically, ergo
Caffiene induces synaptic release and reduce magnesium blockade --> disinhibit synaptic transmission --> central nervous effects --> increased neuronal activity

Systemic: increases electrical impulses and pacemaker function of cardio myocytes (heart fxn & rate!)

Front 31

What is the order of "abuse potential" among drugs?

Back 31

cocaine, amphetamine and methamphetamine (highest abuse potential)
>methylphenidate
> sibutramine and phentermine. (lowest)

Front 32

What is phentermine's therapeutic use?

Back 32

appetite suppressants (short term)

Front 33

Phentermine's side effects?

Back 33

Lower abuse potential
Sympathomimetic effects on heart – use caution in pts w/ hx of CV disease

Front 34

sibutramine moa?

Back 34

Blocking reuptake of catecholamines (NE & DA) and serotonin reuptake

Front 35

Sibutramine uses?

Back 35

Long term weight loss via active metabolites of CYP3A4

Front 36

Sibutramine side effects?

Back 36

Lower abuse potential
Sympathomimetic effects on heart – use caution in pts w/ hx of CV disease

Front 37

caffeine MOA

Back 37

Inhibitor of cyclic nucleotide phosphodiesterases and adenosine receptor antagonists, the latter is believed to be the principal contributor to CNS stimulant effects.

Reduces resting cerebral blood flow

generally disinhibits neuronal activity

Front 38

What is methylxanthine

Back 38

Caffiene

Front 39

Caffeine clinical uses?

Back 39

Used in patients with asthma as a bronchodilator
Use in the US has now been markedly curtailed since the development of beta-agonists, inhaled corticosteroids, and leukotriene antagonists.


--> off label: Sleep apnea in neonatal units accompanied by bradycardia

Front 40

Caffeine pharmalogical effects?

Back 40

CAFFIENE together Binds to receptors and is antagonistic--> prevents ADENOSINE FROM BINDING AND ACTIVATING SIGNAL
--> adenosine REDUCES presynaptic release and stabilize NMDA blockade post synpatically, ergo
Caffiene induces synaptic release and reduce magnesium blockade --> disinhibit synaptic transmission --> central nervous effects --> increased neuronal activity

Systemic: increases electrical impulses and pacemaker function of cardio myocytes (heart fxn & rate!)

Front 41

Caffeine elimination?

Back 41

hepatic metabolism.

Front 42

Caffeine side effects?

Back 42

Tolerance develops to the stimulating effects
Withdrawal syndrome can be identified
Fatigue
Sedation
Headache and nausea (with chronic, high-dose use)

Front 43

modafinil MOA?

Back 43

Mechanism is unknown, but thought:

Interactions with both dopaminergic and noradrenergic systems have been postulated

There are indications that it both inhibits hypothalamic sleep-promoting neurons, and activates pathways promoting wakefulness.

Front 44

Modafinil therapeutic uses?

Back 44

Narcolepsy
Obstructive sleep apnea
Shift work sleep disorder

Increased daytime wakefulness produced by modafinil is not followed by a rebound increase in nonREM sleep.

Front 45

Positives of Modafinil?

Back 45

It has a much lower incidence of stimulant side effects than other drugs
Appears less subject to abuse
Does not produce the same degree of symapthomimetic effects as do ampehetamines

Front 46

Modafinil side effects?

Back 46

High (2x recommended) doses were observed to cause a 9 bpm increase in heart rate and a small increase in BP in healthy subjects.
Caution is advised in patients with cardiovascular problems:
MI
Unstable angina
Left ventricular hypertrophy.

CAUSES STEVEN JOHNSON SYNDROME!!!

Psych: anxiety, mania, suicidal thinking

Front 47

Modafinil metabolism?

Back 47

Metabolism (CYP3A4, some enzyme induction)

Front 48

LSD moa

Back 48

5HT2-A partial agonist
Also enhances glutamate

Front 49

LSD pharmacologic side effects?

Back 49

Hallucinations: synesthesias, dilation of time
Euphoria; or “bad trips”
Peripheral sympathomimetic signs: increase HR & BP, mydriasis
Tolerance, but no withdrawal

LSD only:
Hallucinogen persisting perception disorder (flashbacks)

Front 50

What gives you auditory hallucinations?

Back 50

PCP

Front 51

LSD MOA

Back 51

5HT2-A partial agonist

5-HT2A activation leads to excitation, in part via enhancement of glutamate actions.

Front 52

Are all 5-HT2A agonists hallucinoenics?

Back 52

No. Different agonists at the same receptor may couple to different effector systems.

Front 53

What is the only hallucinogenic that gives you flashbacks?

Back 53

LSD

Front 54

What are physical effects of LSD?

Back 54

dilated pupils
higher body temperature and sweating
nausea and loss of appetite
increased blood sugar
Increased heart rate and blood pressure
Sleeplessness
dry mouth and tremors

Front 55

What is appearance of LSD?

Back 55

odorless
colorless
slightly bitter

Front 56

At what doses do LSD produce psychogenic effects?

Back 56

less than 100mg

Front 57

Does LSD have withdrawal symptoms?

Back 57

no & its not toxic in the human brain

Front 58

Mescaline MOA

Back 58

5HT2-A partial agonists

Front 59

Mescaline effects

Back 59

same as LSD

Front 60

4methylenedioxyamphetamine street name

Back 60

Ecstasy

Front 61

4methylenedioxyamphetamine MOA?

Back 61

5HT2-A partial agonist

5-HT2A activation leads to excitation, in part via enhancement of glutamate actions.

Front 62

4methylenedioxyamphetamine side effects?

Back 62

Hallucinations: synesthesias, dilation of time
Euphoria; or “bad trips”
Peripheral sympathomimetic signs: increase HR & BP, mydriasis
Tolerance, but no withdrawal

MDMA only:
serotonergic neuron degeneration****

Front 63

MDMA effects

Back 63

same as LSD

User experiences:
extreme changes in mood
several different emotions at once
swing rapidly from one emotion to another
delusions and visual hallucinations
Physical effects
dilated pupils
higher body temperature and sweating
nausea and loss of appetite
increased blood sugar
Increased heart rate and blood pressure
Sleeplessness
dry mouth and tremors

Front 64

PCP moa

Back 64

Glutamate antagonist!

(Non-competitive antagonist at NMDA receptors)

// schizophrenia

Front 65

PCP effects

Back 65

PCP can cause visual and AUDITORY hallucinations.
Users commonly exhibit:
Hostile and combative behavior
Paranoid delusions
May be numb and not feel pain
Tachycardia
Hypertension
Sweating
**Anesthetic effects can ensue at higher doses

**Users can progress from agitated behavior with elevated blood pressure, to coma with paralytic dilation of the pupils.

Front 66

marijuana MOA

Back 66

Δ-9 tetrahydro-cannabinol (delta-9-THC) is the active ingredient – acts as cannabinoid receptor partial agonist (mainly CB1, but also CB2)

Front 67

Marijuana therapeutic uses?

Back 67

Recreational drug
Analgesia
Appetite stimulation
Anti-nausea
Reduction of intraocular pressure
Decrease spasticity in MS pts

Front 68

receptor C1 sites of action and action?

Back 68

Found throughout the brain
Highest amounts in:
Basal ganglia
Cerebellum
Hippocampus
Cerebral cortex
Also in:
Spinal cord
Hypothalamus
Thalamus
Peripheral nerve terminals
Testes

Front 69

CB1 MOA

Back 69

The CB1 receptor couples to Gi/o and its activation:
Inhibits adenylyl cyclase
Inhibits neuronal Ca+2 channels
Increases K+ conductance

Front 70

Where is CB2 found?

Back 70

CB2 receptor is found in the periphery on immune system cells (lymphocytes, macrophages) and in the CNS on microglia.

Front 71

Marijuana effects?

Back 71

Psychological effects may include:
Euphoric mellow
High and giddiness
Anxiety
Panic (especially with high doses)
Time dilation
Cognitive and psychomotor impairment ( which may persist beyond the perceived high).

also...

Analgesia
Appetite stimulation
Antinauseant action
Reduction of intraocular pressure
Reduction in spasticity in patients with multiple sclerosis

Front 72

marijuana clearance

Back 72

Hepatic metabolism (note: metabolites detectable in urine/feces up to 5 weeks post-use)

Front 73

Delta-9 tetrahydrocannabinol (Delta-9-THC)

MOA?

Back 73

Δ-9 tetrahydro-cannabinol (delta-9-THC) is the active ingredient –
acts as cannabinoid receptor partial agonist (mainly CB1, but also CB2)

Front 74

Dronabinol MOA

Back 74

Δ-9 tetrahydro-cannabinol (delta-9-THC) is the active ingredient –
acts as cannabinoid receptor partial agonist (mainly CB1, but also CB2)

Front 75

Do Cannabinoids cause dependence?

Back 75

No. Most likely because of their long half life (1.5 days)

Front 76

How do endocannabinoids differ from classical neurotransmitter?

Back 76

1) not synthesized and stored in nerve terminals, and then released when an action potential invades the terminal.

2)depolarization of a post-synaptic cell and the entry of Ca2+, or activation of G-protein coupled glutamate receptors (mGluR) activates enzymes that synthesize endocannabinoids from phospholipids.

Front 77

How are endocannabinoids scaled down?

Back 77

C1 receptors are also on the presynaptic cleft, ergo they can diffuse back across synatpic cleft to act presynaptically -->inhibits presynaptic terminal to scale down activation

Front 78

What are signs of precipitated withdrawal from cannabinoids in humans?

Back 78

Restlessness
Irritability
Agitation
Insomnia
Nausea
GI cramps

Front 79

What are side effects of inhalents?

Back 79

Euphoria
Intoxication (exacerbated by hypoxia and hypercapnea when bagging)
Drowsiness
Slurred speech
Ataxia
Disorientation
Hallucinations
Seizures
Coma

Front 80

What is mescaline MOA?

Back 80

Phenethylamine derivative
5HT2-A partial agonist
Also enhances glutamate

-->similar to LSD, causes hallucinations, etc

Front 81

What is unique about MDMA compared to other Phenethylamine derivative
5HT2-A partial agonist?

Back 81

It has serotonergic neuron degeneration

Front 82

What is dronabinol?

Back 82

ingredient –
acts as cannabinoid receptor partial agonist (mainly CB1, but also CB2)


//marijuana

Front 83

What is acetazolamide? what is its MOA? Where does it work?

Back 83

Carbonic Anhydrase Inhibiting Diuretics

What: Carbonic anhydrase inhibitor.
Where: Proximal convoluted tubule.
How: Increases solute load in urine by ↓ reabsorption of NaHCO3.

Front 84

What is pharmacalogic effect of acetazolamide?

Back 84

Net result:
↑ excretion of Na+, K+, HCO3-, phosphate;
↓ excretion of H+ (↑ urine pH).

Self-limiting!: Causes metabolic acidosis; also macula densa senses ↑ Na+ in urine → afferent arteriole constriction → ↓GFR.
Note: 100% bioavailability.

Front 85

Therapeutic uses for acetazolamide?

Back 85

*Edema (not 1st line)
*Ocular hypertension (open angle)
*Prophylaxis for acute altitude sickness
*Epilepsy (mainly absence seizures in adults—metabolic acidosis suppresses CNS)
*Correct alkalosis

Front 86

Side effects of acetazolamide?

Back 86

Hypersensitivity (due to sulfa structure): bone marrow depression, skin rxn, renal lesions.

Overdose: somnolence, paresthesias.

Alkalization of urine:
*ammonia retention → contraindicated in hepatic cirrhosis/
encephalopathy
*precipitation of Ca-phosphate salts →contraindicated in renal stones
*worsens preexisting acidosis → contraindicated in hyperchloremic acidosis & severe COPD
*↓ urine excretion of weak bases → drug interactions

Front 87

Elimination of acetazolamide?

Back 87

F = 100%,
elimination--renal
t1/2 = 6-9 hrs.

Front 88

What is dorzolamide?

Back 88

Carbonic anhydrase inhibitor:

Where: Proximal convoluted tubule.
How: Increases solute load in urine by ↓ reabsorption of NaHCO3.

Front 89

What is mannitol? Where does it work and what is its MOA?

Back 89

What: Osmotic diuretic.
Where: Thin descending limb.
How: Given in large doses, are freely filtered but undergo limited reabsorption → ↑ solute load in lumen → ↓water reabsorption.

Front 90

What is pharmacologic effect of mannitol? (i.e. excretion, absorption)

Back 90

Net result: ↑ excretion of nearly all electrolytes (Na+, K+, Ca++, Mg++, Cl-, HCO3-, phosphate)

Front 91

What is/are therapautic use for mannitol?

Back 91

*Acute renal failure—prevention & tx (controversial)
*Dialysis disequilibrium (hypoosmolarity of extracellular fluid)
*Ocular hypertension*** closed!
*Intracranial pressure*****
*Estimate GFR
*↑renal excretion of toxic

Front 92

Side effects of mannitol?

Back 92

Expansion of extracellular fluid:
*hyponatremia → headache, nausea, vomiting
*contraindicated in heart failure, pulmonary congestion

Overdiuresis → hypernatremia, dehydration

Contraindicated w/ intracranial bleeding!!!!

Front 93

pharmokinetics of mannitol?

Back 93

F = 100%,
elimination--renal
t1/2 =VERY SHORT

Front 94

What is mannitol's effect on the gradient?

Back 94

Washes out medullary gradient --> less impact from ADH --> less resorption of water

Front 95

Explain furomeside what type of drug is it? where does it act and how?

Back 95

What: Loop diuretic.
Where: Thick ascending limb.
How: Inhibits Na/K/2Cl symporter →

IMPORTANT: acutely increases systemic venous capacitance (via a renally derived mediator, PGs?) and thus decreases cardiac preload and may reduce pulmonary edema even before diuresis occurs.--> FEEL BETTER BEFORE THEY EVEN GET A DROP OF URINE OUT!

Front 96

Pharmacologic effects of furomeside?

Back 96

1) ↓positive potential in lumen, so ↑Ca++ & Mg++ excretion;

2) ↓ NaCl in renal medulla → ↓ medullary osmotic gradient → ↓ ability to concentrate urine

3) Blocks NaCl transport into macula densa, so GFR doesn't ↓

ALSO: furosemide has venodilator action that can ↓ dyspnea by ↓ preload

Front 97

Uses for furomeside?

Back 97

1. Acute pulmonary edema

2 Edema associated with heart failure, cirrhosis, renal failure

3. Hypertension

4. Hypercalcemia--a classic use, but minimal supporting

5. A classic use has been in acute renal failure to convert oliguric to nonoliguric status. This use is not supported by recent meta-analyses—use of furosemide does not improve mortality or decrease the need for transplant or dialysis, and may cause ototoxicity.

Front 98

Side effects of furomeside?

Back 98

↑systemic venous capacitance → ↓cardiac preload, ↓pulmonary edema

*Hypotension, reduced GFR, circulatory collapse
*Hyponatremia
*Hypokalemia --> arrythmias!
*Metabolic alkalosis (losing H+)
*Hypomagnesia
*OTTOTIXICITY!!!
*Hyperuricemia
*increased LDL: HDL & glucose intolerance
*Hypersensitivity!

Front 99

Pharmokinetics of furomeside?

Back 99

RENAL & short half life!

WORK, obviously, from the luminal side of the tubule, and because they are highly bound to plasma proteins must be transported by the proximal tubule organic acid transporter.