Lec 17 & 18 (Anxiety/Epilepsy & Dopamine/Serotonin) Flashcards Preview

Pharm Exam 2 > Lec 17 & 18 (Anxiety/Epilepsy & Dopamine/Serotonin) > Flashcards

Flashcards in Lec 17 & 18 (Anxiety/Epilepsy & Dopamine/Serotonin) Deck (29):
1

Class I ACD Mechanisms (5)
[GABA-A transmission]

1. positive allosteric modulator, increase affinity of GABA for its receptor
-act to increase inhibition of nervous system
2. irreversible (or reversible) inactivation of GABA-T(transaminase)
-inhibits GABA breakdown/catalysis
3. increase GABA synthesis
4. blocks GABA repute
-prolongs signaling
5. protect GABA-A receptor from desensitization

2

Class II ACD Mechanism (1)
[Na+ channel]

1. act to slow rate of Na+ channel recovery from refractory period/ inhibition of action potential
-limits ability of neuron to fire at high frequencies, decreased neuron excitability

3

Class III ACD Mechanisms (1)
[Ca2+ channels]

1. T-type Ca2+ channels play a role in burst firing of action potentials in the thalamus
-ACDs that inhibit these channels

4

Anticonvulsant Drugs - Side Effects + Risks

hepatotoxicity - can induce p450's
double vision
ataxia (loss of coordination)
sedation (with BZDs)
aplastic anemia (lack of blood cell production)

drug interactions, narrow therapeutic window
lack of compliance (due to side effects)
dangers with use of generics

5

original drug for anxiety disorder treatment

alcohol

6

effects of benzodiazepines (inc dose)

mild sedation
-anxiolytic action
strong sedation
-impaired cognition, retrograde amnesia, used for surgery
hypnosis
-sleep
stupor

7

mechanism of action - BZDs

positive allosteric modulation of GABA-A receptor
-bind to a separate site
-increase affinity of GABA for its receptor, a LGIC for Cl- (inhibitory)
-influx of Cl- into the cell hyperpolarizes and leads to decreased ability to reach threshold/fire AP

8

BZD administration

-oral (p.o) safer than i.v. (rapid CNS distribution, risk of overdose)
-lipophilic, high bioavailability, rapid onset of CNS effects
-active and inactive metabolites of varying half-lives

9

BZD elimination

-primarily cleared via biotransformation, CYP450 and/or glucuronide conjugation

10

BZD precautions

-can have additive actions with other CNS depressants, especially alcohol
-individuals with hepatic dysfunction
-individuals taking drugs that are CYP450 inhibitors

11

BZD withdrawal

rapid discontinuation can lead to seizures or anxiety-like symptoms. want to gradually discontinue

12

BZD overdose

can give flumezanil, a direct antagonist of GABA-receptor
-blocks BZD binding site

13

Risk of Baribituates

-low therapeutic index/safety margin
-high abuse liability, risk of respiratory depression
-acts at multiple receptors, not selective
-induces p450 enzymes
-no antidote

14

BZD sensitivity at GABA-Rec

gamma subunit

15

allosteric modulators of GABA-rec

barbiturates
propofol
(at high concentrations propofol and barbiturates act as direct agonists)
alcohol
benzodiazepines

16

GABA-A Rec Subtype: alpha-5

mediates cognitive enhancing effects

17

GABA-A Rec Subtype: alpha-2/3

mediated anxiolytic and anticonvulsant efects

18

GABA-A Rec Subtype: alpha-1

amnesic/sedative (sleep inducing), muscle relaxant

19

Parkinson's: Physical Characteristics

Tremor: resting - depressed with voluntary movement, unilateral
Rigidity
Akinesia: lack of movement, slowness (bradykinesia)
Postural Instability

20

Parkinson's: Neuropathological Features

neurodegenerative disorder
-degeneration of the dopaminergic neurons in the niagrostriatal pathway, which controls and coordinates movement

21

Dopamine Synthesis
(enzymes and intermediates)

tyrosin --> L-dopa (tyrosine hydroxylase)
L-dopa --> dopamine (dopa decarboxylase)
dopamine degredation
-MAO and COMT

22

Parkinson's: Pharmacotherapy (3)

1. increased rate of dopamine synthesis
-addition of L-dopa, precursor
-Carbidopa: inhibits peripheral dopa decarboxylase, increases amount of L-dopa entering brain

2. increase L-dopa duration/decrease DA degredation
-carbidopa inhibits dopa-decarboxylase
-enzymes to inhibit MAO-B or COMT

3. mimic dopamine
-administration of D2-receptor. decrease amount of L-dopa needed to increase dopamine signaling

23

Parkinson's: Non-Pharamcological Strategy

deep brain stimulation
-electrically inhibits subthalamic nucleus, decreases excessive inhibition to thalamus

24

Substantia Niagra

area of basal ganglia with dopaminergic neurons
-degradation with Parkinson's, loss of dopamine cells

25

Parkinson's: Pharmacotherapy Side Effects

nausea, arrhythmias, orthostatic hypotension, on-off phenomenon, dyskinesias, psychosis

26

Classes of Antidepressants (4)
(mechanism of action, side effects)

1. SSRI's
-sexual dysfunction, nausea, weight
2. Atypical: NE/DA/5-HT reuptake inhibitors, 5-HT2A/alpha2 receptor antagonists
-nausea, weight gain, sexual dysfunction
3. MAO Inhibitors: decrease monamine degradation
-hypotension, weight gain, anticholinergic, tyramine storm, manic effects
4. Lithium: primarily for bipolar to prevent mood swings. substitutes for Na+ on neurons and alters receptor-mediated signaling
-narrow TI, nausea, tremor, kidney dysfunction, overdose can lead to coma/death

27

Schizophrenia: Symptoms

-Positive: delusion, hallucination, disorganized speech, catatonia
-Negative: decreased affect, poor speech (alogia), decreased movement (avolition), lack of pleasure (anhedonia)

28

Schizophrenic: biological effects, dopamine hypothesis

-significant genetic component
-atrophy of regions (increased neuron density), enlarged ventricles
-thought due to overactive dopaminergic neurons. see drug induced psychosis. explains therapeutic actions, but not etiology.

29

Classes of Antipsychotics

-Typical (ie haloperidol): inhibit D2-receptors
-Atypical (i.e. clozapine): inhibit 5-HT2, D4 and- D2 receptors
-Side effects: sudden cardiac death, tardive dyskinesia, metabolic syndrome, agranulocytosis (with clozapine, no WBCs)