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Flashcards in Pharm 2.2 Deck (32)
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0
Q

What receptors make up the D1 receptor family and what do they do?

A

D1 and D5
D1 is in Striatum and Neocortex
D5 is in Hippocampus and Hypothalamus
Both elevate cAMP and PIP2 hydrolysis -> elevate intracellular Ca and PKC activation

1
Q

What is the Dopamine hypothesis of Schizophrenia?

A

DA receptor is at the center of schizophrenia
Over production of receptor a possibility
Hypothesis based on observation that DA antagonists diminish syptoms and agonists induce / exacerbate.
All effective pharmacologic therapies block DA receptors

2
Q

What receptors make up the D2 receptor family and what do they do?

A

D2,3,4
D2: striatum, substantia nigra, pituitary
D3: olfactory tubercle, n.acumbens, hypothalamus
D4: frontal cortex, medulla, midbrain
decrease cAMP, increase K+ currents, decrease voltage dependent Ca++ currents

3
Q

Where are most DA receptors in the brain located? What is the role?

A

Nigrostriatum
80% of receptors
modulates movement and learned habits

4
Q
What role does DA play in the following areas, how do they relate to schizophrenia, what impact do APDs have?
Nigrostriatum
Mesolimbic
Mesocortical
Hypothalamic
Area Postrema
A

Nigrostriatum: regulates movement and learned behaviors (APD side effects -> tardive dyskinesia)
Mesolimbic: motivation, goal-directed thinking, affect, reward (overactive, related to positive symptoms. APDs help)
Mesocortical: cognition (hypofunction -> negative symptoms. APDs don’t really help)
Hypothalamic: hormone reg
Area Postrema: emesis (outside BBB)

5
Q

what is neuroleptic malignant syndrome and how is it treated

A

Caused by sensitivity to DA blockade by APDs
-fever + parkinsonism, autonomic instability, rhabdomyolysis (elevated CPK)

Treatment: bromocriptine, dantrolene

6
Q

Differentiate tardive dyskinesia and parkinsonism as related to APD therapy

A

tardive dyskinesia is seen w/ chronic APD use and is irreversible
-masked by increasing dose of APD, worsens w/ withdrawal

parkinsonism occurs in the short-term and is easily treated (adjust meds)

Both induced in proportion to affinity for D2 receptor of APD in use.

7
Q

Why would APDs be used pre-surgically?

A

Older APDs used for anti-emetic effect (H1 blockade)

8
Q

What is schizoaffective disorder?

A

Schizophrenic symptoms plus mood disorder - bipolar, depression

Treat w/ APD plus antidepressant, lithium, valproate

9
Q

What is the mean time range from diagnosis to death in Parkinson’s Disease?

A

15 years

10
Q

What cells are primarily effected in Parkinson’s disease?

A

Midbrain DA cells, especialy nigrostriatal
-responsible for learning and execution of complex purposeful motor patterns
>80% decrease in cell population needed for symptoms

11
Q

What is Carbidopa?

A

Peripheral aromatic amino acid decarboxylase inhibitor

Given to PD patients with Levodopa - improves absorption - reduces peripheral metabolism

12
Q

In PD patients what are the preferred treatments for:
Depression?
Psychosis?
Dementia?

A

Depression: SSRI
Psychosis: Clozapine - atypicals preferred
Dementia: Cholinesterase inhibitors

remember that PT and mental exercise is recommended!

13
Q

What is the current progression of PD treatment?

A

Delay treatment - manage w/ lifestyle changes as long as poss.

Anticholinergic, MAO-B inhibitor, and/or amantadine -> Direct DA agonist -> Sinemet -> add COMT inhibitor -> use apomorphine as needed for “off” periods -> consider surgical intervention (DBS)

14
Q

How is essential tremor managed?

A

Beta blockers (propanolol, metaprolol) or low-dose aniepileptics (primadone, topiramate)

Refractory patients may be treated w/ DBS - >80% complete effectiveness

15
Q

Features and course of Alzheimer’s Disease

A

Progressive and fatal disease
Begins w/ short-term memory difficulty -> difficulty with common tools and calculation -> immobilization

Death usually due to complications of immobilization (pneumonia, PE in 6-12 years following diagnosis)

16
Q

Pathophysiology of Alzheimer’s Disease

A

Neurodegeneration - atrophy of cerebral cortex
B-amyloid plaque formation - hippocampus and associative cortex
Neurofibrillary tangles - microtubule breakdown due to hyperphosphorylation of tau subunit

More plaques and tangles -> more cognitive impairment

17
Q

What genetic risk factors are linked to Alzheimer’s disease?

A

Linked to Amyloid Precursor Protein (APP) and processing proteins presenilins (PS1, PS2): alternate cleavage of APP -> plaque formation

Lipid Transfer Apolipoprotein E4 (APOE-4): 15x increased risk - unknown why
WBC receptor TREM2 - mutations -> increased risk

18
Q

What evidence has been found that supports the APP AB hypothesis of Alzheimer’s disease?

A

Icelandic study identified A673T coding mutation in APP that is highly protective against AD, even in presence of ApoE4

mutation -> 40% reduction in amyloidogenic peptide formation

19
Q

What are characteristics of Lewy Body dementia?

A

Progressive cognitive decline with dramatically fluctuating cognition.
Patients may experience vivid hallucinations, autonomic disregulation, REM sleep disturbances

20
Q

What is the risk in off-label use of antipsychotics for treating hallucination, agitation, delusion in Alzheimer’s patients? What about LBD?

A

2x increased risk of death due to MI, pneumonia, infections with both APD and atypicals.

LBD: very high risk of adverse response to APDs: Parkinsonism, sedation, malignant neuroleptic syndrome*

21
Q

Semagacestat

A

gamma secretase inhibitor
gamma secretase cleaves APP
clinical trial halted due to dose-dependent decrease in cognitive function

22
Q

Plasmin

A

Degrades plasmin, contributing to thrombolysis / fibrinolysis

23
Q

What is primary and secondary hemostasis?

A

Primary: formation of a platelet plug
Secondary: addition of fibrin to platelet plug

24
Q

What is Heparin?

A

Indirect Thrombin Inhibitor
Prevents thrombus formation via AT III and factor Xa
Consists of a heterogenous mixture of sulfated mucopolysaccharides

25
Q

What is the difference in binding between LMWH and HMWH?

A

LMWH: binds Xa and not thombin
HMWH: binds thrombin and not Xa

26
Q

What are heparin’s targets in the coagulation cascade?

A

IXa, Xa, Thrombin

27
Q

For what uses are LMWH and fondaparinux approved?

A

LMW: PE, venous thrombus, unstable angina
-given as sc injection (more predictable than HMWH - does not require lab monitoring)
Fondaparinux: Thromboprophylaxis in settings of: PE, DVT, hip and knee surgery

28
Q

What is the antidote for heparin OD?

A

Protamine - heparin antagonist

29
Q

What is warfarin’s target and effect?

A

Targets Vitamin K Epoxide Reductase used for recycling of Vitamin K in synthesis of Ca++ dependent clotting factors Prothrombin, VII, IX, X and protein C

Result: clotting inhibition

30
Q

What is INR?

A

ratio of Patients PT and mean of labs ‘normal’ PT

Higher INR associated with higher risk of bleeding

31
Q

What is the antidote for excessive fibrionolysis (tPA OD)?

A

Aminocaproic Acid

Blocks interraction between fibrin and plasmin