Pharmacology Flashcards
(41 cards)
Which TCA is selective for Norepinephrine Transporters?
Desipramine
State the MOA of MAOi
MAO inhibitors (MAOIs) increase biological availability of monoamines (Dopamine, Serotonin and Norepinephrine) by preventing their degradation.
State the 2 major forms of MAO and what neurotransmitters they break down
MAO-A: Serotonin (mainly broken down by MAO-A), Dopamine, Norepinephrine
MAO-B: Dopamine
ADRs of MAOi
1) Postural hypotension
2) Restlessness and insomnia (due to CNS stimulation)
3) Serotonin Syndrome (hyperexcitability, myoclonus, inc muscle tone, loss of consciousness)
State the MOA of Cheese Reaction
Tyramine competes with norepinephrine for vesicular storage leading to increased NE release into the synapses causing sympathomimetic effect
ADRs of TCAs (3 classes of ADR)
1) Sedation (from H1 antagonism)
2) Postural hypotension (from α adrenoceptor sympathetic block) and reflex tachycardia (not listed)
3) Constipation, dry mouth, urinary retention, blurred vision (from muscarinic receptor antagonism)
What 2 receptors do most atypical antipsychotics block?
D2 and 5HT-2A
MOA of most antipsychotics involve
Blocking of Dopamine receptors in the mesolimbic tract
The extrapyrimidal pathway involves which parts of the brain?
Basal ganglia, Substantia nigra and Striatum
Between D1,2,3,4, which one is the most culpable in causing EPSE?
D1
State the 4 potential reasons why atypical antipsychotics produce less EPSE
o Potent 5-HT2A receptor antagonism vs. weak D2 antagonism -> lower EPS and higher efficacy against negative symptoms
Clozapine, olanzapine
o High D3 to D2 antagonism ratio favours actions on the nucleus accumbens over the striatum (mostly D1, D2 present).
Amisulpride
o High D4 to D2 antagonism ratio favours actions in the prefrontal cortex over the striatum.
Clozapine
o High D2 to D1 antagonism ratio reduces impact of antagonism in the striatum (D1 is the worst in causing EPS)
Amisulpride, risperidone
A higher D2 to D1 antagonism ratio should confer less complete blockade of dopaminergic function in the striatum as D2 antagonism will increase dopamine release.
State the MOA of TCAs
Inhibit the reuptake of Monoamines (Dopamine, NE, Serotonin), causing build up in the synaptic cleft
State the monoamine theory of depression
Deficits in monoamine neurotransmitters
(noradrenaline, dopamine and 5 HT) cause depression.
What are the general side effects of SSRI (7)
1) GI
2) Sexual dysfunction
3) Insomnia
4) Sedation
5) Bleeding risk
6) SIADH (and or hyponatremia) (esp for elderly)
7) Serotonin syndrome (hyperthermia, tremor, CV collapse)
State the Schizo symptoms that Antipsychotics do not have much effect on
Negative symptoms (affective flattening aka no emotion, avolition aka no interest)
State the receptor affinity of Amisulpride
selective D2/D3 antagonist (but recently also reported to have 5-HT7 antagonism)
State the potential MOAs of treatment of neurodegenerative diseases (6)
1) Increase synthesis of neurotransmitter (NT) (e.g by inc amt of precursor)
2) Destroy enzymes that degrade NT
3) Inc release of NT from terminal button
4) Bind to autoreceptor and block their effect on inhibiting NT release
5) Block reuptake of NT
6) Bind to postsynaptic receptor and inc effect of NT
Pathophysiology of Parkinsons
- Impaired clearing of abnormal/damaged intracellular proteins by ubiquitin-proteasomal system.
- Failure to clear toxic proteins lead to aggregation of aggresomes -> induce oxidative stress and molecular abnormalities -> Degeneration of dopaminergic neurons (more metabolically active -> more vulnerable) with Lewy body (a type of aggresome) inclusions in substantia nigra -> dysfunction of nigrostriatal pathway -> No release of inhibition that allows motor system to become active -> hypokinetic state
State how the loss of dopaminergic input leads to motor symptoms for direct and indirect pathway
Direct pathway:
- Loss of dopaminergic input lead to hypoactivation of excitatory D1 receptor that weaken strialtal inhibition of GPi (Globus pallidus internal) -> Hypokinesia
Indirect pathway:
- Loss of dopaminergic input lead to hypoactivation of inhibitory D2 receptor that strengthens striatal inhibition of GPe (Globus pallidus external) -> Hypokinesia
State MOA of COMT inhibitors
o Blocks COMT conversion of dopamine/ L-DOPA into an inactive form leading to:
- More levodopa being available to enter the brain (reduces required dose)
- Increases duration of each dose of Levodopa -> beneficial in treating “wearing off” responses
List the names of COMT inhibitors
Entacapone, Tolcapone
State ADR specific to both Pramipexole and Ropinirole (3)
Sedation, somnolence, daytime sleepiness
State ADR specific to Pergolide (2)
Peritoneal fibrosis, cardiac valve regurgitation
State the MOA of Amantadine (4)
o Enhance release of stored dopamine
o Inhibit presynaptic uptake of catecholamine
o Dopamine receptor agonist (Upregulates D2 receptors, ↑ sensitivity of D2 receptors)
o NMDA receptor antagonist (anti-glutamate)
