Pharm Movement D/os; Gaba Agonists

Front 1

5 methods to increase DA tone

Back 1

1) Increase availability of precursor (L-DOPA)

2) Enhance DA release

3) Direct DA agonists

4) Inhibiting breakdown of DA via COMT inhibitors

5) Inhibiting breakdown of DA by MAO-B inhibitors

Front 2

L-DOPA --> DA by what enzyme?

Back 2

DOPA decarboxylase

Front 3

L-DOPA: cause of side effects

Back 3

95% of it is used peripherally --> massive amounts of peripheral DA

Front 4

L-DOPA: side effects

Back 4

excessive peripheral DA results in
A) Nausea/vomiting - stim. of area postrema

B) orthostatic htn

C) Cardiac irregularities

D) Dyskinesias

E) Psych and behavioral problems

F) Somnolence

G) Impulse control problems

H) On-off response

Front 5

On-off response: defn

Back 5

fluctuations between severe dyskinesia and akinesia, possibly from rising and falling levels of L-DOPA.

(Controlled release formulation of L-DOPA (Sinemet) helps with this)

Front 6

Cardiac irregularities in L-DOPA: What is cause?

Back 6

Stimulation of β1-adrenergic receptors by massive DA in heart

Front 7

3 important drug interactions with L-DOPA

Back 7

1) Pyridoxine (B6): enhances peripheral decarboxylation of L-DOPA

2) MAO-inhibitors: can result in hypertensive crisis

3) Antipsychotics: block stim of DA receptors

Front 8

Amantadine: MOA

Back 8

NMDA-channel blocker. Thought to cause increase DA release.

Front 9

Amantadine: problems

Back 9

Tolerance rapidly develops

Used to help patients thru exacerbation times

Front 10

Ergot derivatives like bromocriptine: MOA

Back 10

Stimulate D2 DA receptors on postsynaptic membrane.

Front 11

Ergot derivatives like bromocriptine: problems

Back 11

less dyskinesia, but more mental side effects (hallucinations)

Causes N/V

Front 12

Ropinirole: MOA

Back 12

D2 DA agonist (non-ergot)

Front 13

Pramipexole: MOA

Back 13

D3-selective DA agonist

Acts selectively on D3 presynaptic inhibitory autoreceptors.

Front 14

Apomorphine: MOA

Back 14

injectable, non-ergot DA agonist to treat periods of immobility in advanced PD

Must be taken with antiemetics

Front 15

pramipexole is also approved for _______

Back 15

restless legs syndrome

Front 16

Entacapone: MOA

Back 16

COMT inhibitor - reduces metabolism of DA and L-DOPA

Front 17

T/F Entacapone must be given with L-DOPA

Back 17

T

Front 18

Selegiline: MOA

Back 18

MAO-B inhibitor. Prevents breakdown of DA (and theoretically prevents formation of neurotoxins in CNS.)

Front 19

Selegiline: added benefits

Back 19

MAY slow progression of PD. But once it's D/Cd, patients rapidly deteriorate.

Front 20

Why is it safe to give selegiline with L-DOPA?

Back 20

Because it inhibits MAO-B, which preferentially metabolizes DA (Not NE, 5HT, or tyramine)

Front 21

Rasagiline: MOA

Back 21

MAO-B inhibitor (like selegiline)

Front 22

trihexyphenidyl: MOA

Back 22

Anticholinergic (antimuscarinic).

Greater blockage of muscarinic ACh-Rs in central rather than peripheral sites.

Front 23

trihexyphenidyl: Side effects

Back 23

Related to peripheral anticholinergic action: Dry mouth, blurred vision, tachycardia, constipation.

Also have CNS effects including confusion and hallucinations.

Front 24

benztropine: MOA

Back 24

antimuscarinic, central > peripheral.
<b>also blocks re-uptake of DA</b>, acting to block excess cholingeric tone and enhance DA tone.

enztropine antagonises the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early Parkinson's disease.

Front 25

There is a loss of neurons containing what (4) in the striatum in HD?

Back 25

GABA

ACh

Substance P

Enkephalin

Front 26

2 approaches to HD treatment

Back 26

1) Reduce DA

2) Enhance ACh

Front 27

Antipsychotic drugs: MOA for HD

Back 27

DA receptor antagonists

Front 28

tetrabenazine: MOA

Back 28

vesicular monoamine transporter-2 (VMAT-2) inhibitor. Results in reduced stores of NE, 5HT, and especially DA.

Front 29

tetrabenazine: side effects/risks

Back 29

Can worsen depression.

Carries increased risk of suicide.

Front 30

What types of antidepressants should be used in HD?

Back 30

Those with NO anticholinergic properties - ex, fluoxetine, carbamazepine

Front 31

Wilson’s Disease: pathophys

Back 31

Mutation in gene that results in <b>accumulation of Copper in organs</b> especially affecting liver and brain.

Front 32

Wilson’s Disease: tx

Back 32

CHELATING CU2+ to relieve symptoms.

Penicillamine is the chelator.

Front 33

Triethylenetetramine/trientine: MOA

Back 33

The hydrochloride salt of triethylenetetramine, referred to as trientine hydrochloride, is a chelating agent, and is used to bind up and remove copper in the body to treat Wilson's disease, particularly in those who are intolerant to penicillamine.

Front 34

Penicillamine: MOA

Back 34

effective chelator of Cu2+

Front 35

Penicillamine: toxicities/side fx

Back 35

Drug-induced lupus
Nephrotic syndrome

Front 36

Rotigotine: MOA and use

Back 36

non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS)

Front 37

MAO-B inhibitors used in PD

Back 37

Rasagiline
Selegiline

Front 38

Spasticity: defn

Back 38

increased muscle tone due to flexor or extensor muscle spasms caused by an increase in velocity-sensitive stretch reflexes

Front 39

Stretch reflex: defn

Back 39

muscle contraction in response to stretching within the muscle. It is a monosynaptic reflex which provides automatic regulation of skeletal muscle length.

Front 40

_____ regulate how sensitive the stretch reflex is by tightening or relaxing the fibers within the spindle.

Back 40

Gamma motoneurons

Front 41

stretch reflex is aka

Back 41

myotactic reflex, deep tendon reflex, knee-jerk reflex

Front 42

T/F Drugs acting "centrally with little sedation" are effective for spasticity.

Back 42

F. They may act merely thru sedation but are for ACUTE MUSCLE SPASMS ONLY

Front 43

Benzos: MOA at spinal cord level

Back 43

act at the BNZ (benzo) receptor at the GABA-BNZ-Cl-ionophore complex, at least partially at the spinal cord level, to increase affinity of GABA receptor for GABA.

Front 44

Which benzo is useful for acute muscle spasms?

Back 44

Diazepam

Front 45

Baclofen: MOA

Back 45

GABA-B agonist.

Acts at level of spinal cord in reflex circuit involving g-motoneurons.

Front 46

Baclofen: indications

Back 46

spasticity associated with MS and traumatic SCI

Front 47

Baclofen: side effects

Back 47

If withdrawn rapidly, can cause seizures and hallucinations

Front 48

Tizanidine: MOA

Back 48

centrally acting α2 adrenergic agonist.

Front 49

Tizanidine: indications

Back 49

Spasticity, cramping, and tightness of muscles caused by MS, diplegia, back pain, or certain other injuries to the spine or central nervous system.

Front 50

Dantrolene: indications

Back 50

Spasticity of CEREBRAL origin.

Ie, MS, cerebral palsy, hemiplegics, paraplegics.

Also good for malignant hyperthermia.

Front 51

Dantrolene: particularly effective for _______ movements

Back 51

athetoid (involuntary convoluted, writhing movements of the fingers, arms, legs, and neck)

Front 52

Dantrolene: MOA

Back 52

Binds to ryanodine receptor (within intracellular Ca2+ channel), inhibits release of Ca2+ from SR, thus interfering with excitation-contracting coupling.

Front 53

Dantrolene: side effects

Back 53

Generalized muscle weakness

hepatotoxicity

Front 54

Botulinum toxin: MOA

Back 54

inhibits release of ACh at NMJ

Front 55

Botulinum toxin: indications (re: movement disorders)

Back 55

cervical dystonia

Front 56

Tizanidine: metabolism

Back 56

CYP1A2 (potential drug interactions)

Front 57

A 70-year-old male reports prowlers in his house, although his wife never sees anyone. He is being treated with Sinemet (l-dopa + carbidopa) for Parkinson’s disease. What should be added?

Back 57

Clozapine

Front 58

hypnosis: defn

Back 58

drowsiness and induction of sleep

Front 59

Most sedative-hypnotics act involving the ______ receptor

Back 59

GABA-A

Specifically, the GABA-benzo-chloride ionophore complex.

Front 60

T/F Most sedative-hypnotics have the capacity to produce a withdrawal syndrome.

Back 60

T (physical dependence)

Front 61

T/F Most sedative-hypnotics exhibit an analgesia effect.

Back 61

F

Front 62

Binding of agonist to GABA receptor results in influx of ___ ions

Back 62

Cl-

results in hyperpolarization (more difficult to conduct AP)

Front 63

Barbiturates: binding site and implications

Back 63

Bind to a site within the Cl- channel, increasing duration of channel open time.

Front 64

Benzos: binding site and implications

Back 64

Bind to BNZ receptor, increasing affinity of GABA receptor for its ligand.

Front 65

Why are benzos more safe than barbiturates?

Back 65

Benzos rely on GABA present endogenously, wherease barbiturates OPEN THE CHANNEL DIRECTLY.

Front 66

GABA-Benzodiazepine-Cl- Ionophore Complex: Structure and Subunits

Back 66

Five subunits. Most commonly two &alpha;, two &beta;, and one &gamma;.

Front 67

T/F Barbs exist as tautomers at physiological pH.

Back 67

T

Front 68

tautomer: defn

Back 68

isomers (structural isomers) of organic compounds that readily interconvert by a chemical reaction called tautomerization

Front 69

____ of barbiturates determines onset and duration of action.

Back 69

Lipid solubility

Front 70

Barbiturates: What does Tissue Redistribution determine?

Back 70

duration of action

Front 71

Barbiturates: Metabolism

Back 71

Metabolism by CYPs (many); then excreted by kidneys

Front 72

Barbiturates: absolute contraindication

Back 72

Acute intermittent porphyria
&delta;-aminolevulinic acid (ALA) synthetase

Front 73

Barbiturates: CNS effects

Back 73

1) Hyperalgesia
2) Decrease in REM sleep
3) Respiratory depression

Front 74

T/F barbiturates reduce cerebral metabolism and hence cerebral blood flow.

Back 74

T

Front 75

T/F Benzos affect metabolism of other drugs similarly to barbiturates.

Back 75

F

Front 76

Benzos: excretion

Back 76

Water-soluble glucuronides by kidneys

Front 77

Benzos: distribution

Back 77

lipid solubility determines onset of action.

Many have active metabolites which play a role in duration of action.

Front 78

Benzos: metabolism

Back 78

Many are metabolized by liver microsomal enzymes (CYPs) to ACTIVE METABOLITES that can accumulate.

Front 79

Lorazepam: metabolism and excretion

Back 79

Directly glucuronidated and then excreted.

Front 80

Benzos: sleep effects

Back 80

decrease stage 4 sleep

Front 81

Benzos that have the least effect on REM sleep that were developed to treat insomnia

Back 81

Triazolam
Flurazepam

Front 82

Benzos used to induce sleep or maintain anesthesia

Back 82

Diazepam
Lorazepam
Midazolam

Front 83

Zolpidem, zaleplon, eszopiclone: MOA

Back 83

Non-benzo drugs that bind selectively to one benzo receptor subtype.

Front 84

Zolpidem, zaleplon, eszopiclone: indication

Back 84

Short-term treatment of insomnia

Front 85

competitive benzo antagonist that can be used in OD situations

Back 85

flumazenil

Front 86

T/F Flumazenil does not reverse effects of Zolpidem, zaleplon, eszopiclone

Back 86

F (These bind to a benzo receptor)

Front 87

Barbiturates vs Benzodiapines: Sleep effects

Back 87

Barbiturates: decrease REM sleep Benzodiapines: decrease stage 4 sleep

Front 88

When treating insomnia, rule out _______ first.

Back 88

sleep apnea

Front 89

methohexital : MOA

Back 89

binds to a distinct site which is associated with Cl− ionophores at GABAA receptors.[1] This increases the length of time which the Cl− ionopores are open, thus causing an inhibitory effect.

Front 90

methohexital : indication

Back 90

induction of anesthesia

Front 91

Propofol : uses

Back 91

Rapid induction of anesthesia
Rapid uneventful recovery
Anti-emetic properties
Apnea and bradycardia

Front 92

Propofol : side effects

Back 92

Apnea and bradycardia

Front 93

Dexmedetomidine: MOA

Back 93

selective &alpha;2 agonist

Front 94

Dexmedetomidine: indications

Back 94

use as adjunct to anesthesia, reduces heart rate and blood pressure associated with intubation

Front 95

Ramelteon: MOA

Back 95

Melatonin receptor agonist

Front 96

Advantages of Dexmedetomidine:

Back 96

Cardiovascular stability - attenuates hypertension and tachycardia

No respiratory depression

Patients are often arousable and responsive

Reduces anesthetic and opioid requirements

Front 97

Disadvantages of Dexmedetomidine:

Back 97

Sympatholysis with hypotension and bradycardia

Transient hypertension may occur during loading infusion

Nausea

Front 98

phenobarbital overdose: tx

Back 98

Alkalinization of urine plus supportive therapy