Pharm General Flashcards
(142 cards)
1
Q
How is histamine made?
A
rapidly broken down to inactive metabolites (MAO-B)
2
Q
Autacoid
A
released and act locally includes histamine, serotonin, prostaglandins, leukotrienes, kinins
3
Q
Major role of histamine
A
immune response, NT in CNS
4
Q
Where is histamine found?
A
NT in periphery widespread in skin lung etc and synthesized and stored in mast cells and in CNS
5
Q
H1 histamine receptor location
A
smooth muscle, endothelium, CNS
6
Q
H2 histamine receptor location
A
vascular smooth muscle, cardiac muscle, gastric smooth muscle
7
Q
Post receptor response of H1
A
Inc NO and Inc cGMP
8
Q
Post receptor response of H2
A
Increase cAMP
9
Q
What induces histamine release?
A
allergic rxn (type I hypersensitivity), inflammation, mechanical release and drugs (opioids)
10
Q
What blocks release of histamine?
A
epinephrine and cromolyn (not substitute for epi)
11
Q
What is the effect of histamine binding to smooth muscle cell?
A
phosphorylates MLCK and causes contraction
12
Q
What is the effect of histamine binding to endothelial cell?
A
dephosphorylation of MLCP and relaxation
13
Q
What does histamine regulate in CNS?
A
wakefulness, appetite and body temperature
14
Q
Histamine toxicity in fish
A
nausea, vomiting, HA
suppressed by H1 receptor blockers
15
Q
What are antihistamines most effective to treat?
A
urticaria and allergic rhinitis
16
Q
What is the stimulus for cortisol synthesis?
A
ACTH
17
Q
What is stimulus for aldosterone synthesis?
A
angiotensin II and K+
18
Q
What is the pathway of regulation of glucocorticosteroid synthesis?
A
circadian rhythm and stressors
(or immune system) cause CRH to be released from hypothalamic neurons and go to anterior pituitary where ACTH is released which stimulates cortisol release (neg FB loop)
19
Q
Why doesn’t aldosterone provide feedback inhibition on ACTH secretion?
A
levels are too low
20
Q
What is the mechanism of ACTH on cortisol secreting cells in adrenal cortex?
A
ACTH binds to receptor and increased cAMP activates PKA which phosphorylates cholesterol ester hydrolase and more free cholesterol is formed
21
Q
coactivators
A
facilitate steroid response
22
Q
corepressors
A
inhibit steroid response
23
Q
How do glucocorticoids suppress inflammation?
A
dec production of prostaglandin/leukotriene products which inhibits A2 and decreased synthesis of COX2
24
Q
What normal physiological functions are under control of cortisol?
A
mobilizes AA in response to prolonged fast
25
What is a glucocorticoid response element (GRE)?
specific nucleotide sequence that is recognized by steroid hormone receptor hormone complex
26
How do you inhibit inflammatory events via glucocorticoid receptor?
increase Annexin A1 and decrease COX 2 and TNF alpha synthesis
27
What does annexin A1 do?
inhibit PLA2
28
What is the role of TNF?
transmits signals from immune cells for induction of inflammation
29
Why cant glucocorticoids bind equally to mineralocorticoid receptor?
enzyme (11B-HSD2) converts cortisol to cortisone which cannot bind to receptor
30
Why does eating excessive amounts of licorice cause HTN?
glycyrrhizic acid Inhibits 11B-HSD2 so cortisol binds to mineralocordicoid receptor and causes Na uptake
31
What causes airway increase in asthma?
mucus, thickened wall, smooth muscle constriction, narrowed airway
32
Mast cell effect on airways
decreases diameter and increases mucus secretion
33
Maintenance asthma medications
anti-inflammatory-affect airway responsiveness to stimulus
34
Quick relief medications
bronchodilators-affect airway resistance (open up airways)
35
What is the optimal particle size inhaled with inhaler?
2-5 micrometers
36
What is the most effective treatment in preventing asthma attacks?
inhaled corticosteroids (ICS)
37
Why is fluticasone good to use with β2 agonist?
It increases the number of β2 receptors
38
What is most common pphx for asthma?
ICS and β2 agonist
39
Asthma is NOT adequately controlled if rescue inhaler is used more than how many times/ week?
2
40
What is datura stramonium?
atropine bronchodilator plant
41
COPD
presence of airflow limitation that is not fully reversible with or without presence of sx
42
Sx of COPD
cough with mucus production, dyspnea, wheezing
43
What are the catecholamines?
epinephrine (adrenal), NE (post ganglionic), isoproterenol, dopamine (renal and mesentery beds) and dobutamine
44
Where are B1 receptors?
heart
45
What happens when you activate B1 receptors in the heart?
increase HR, conduction and contractility
46
Where are a1 receptors?
blood vessels and sphincters
47
What happens when a1 receptors are activated?
constriction
48
What happens when B2 receptors are activated?
dilation
49
Where are B2 receptors located?
blood vessels and uterus
50
What is renin release regulated by?
B1
51
What decreases mobility and tone in GI tract?
a1B2
52
What is the function of a2 receptor?
sense how much NE is there (if theres a lot BP is high)
53
Why do you get reflex tachycardia with alpha1 blockers?
a2 is trying to counteract the decrease in BP so increases NE output which will increase HR
54
Why is tachycardia worse in non-selective alpha blocker?
alpha 2 is also blocked and can't regulate the amount of NE so HR is increasing more
55
What is epi reversal?
when you give epi in presence of alpha blocker and there is no "pressor" response (no increase in BP)
56
What is selectivity issue with beta blockers?
want to block B1 not B2 because if you block B2 you will have bronchoconstriction
57
Low levels of which lipoprotein puts people at risk for coronary artery disease?
HDL
58
What are mechanisms for replenishing hepatic cholesterol pool?
↑ biosynthesis of cholesterol
| ↑ LDL receptor expression leading to ↑ LDL clearance from blood
59
What is fiber good for?
absorbs cholesterol, slows cholesterol absorption and ↑ GI motility
60
What do statins structurally look like?
HMG CoA which is eventually converted to cholesterol
61
What does PCKS9 do?
binds to and interacts w/ LDL receptor to degrade it
62
How do statins indirectly lower LDL levels?
Increasing hepatic LDL receptor expression
63
What does PCSK9 do?
binds to and degrades LDLR
64
What is stable angina?
narrowing of epicardial coronary artery, ischemia presents upon exercise at predictable level
65
What is acute coronary syndrome (ACS) AKA variant angina?
vasospasm of coronary artery
66
What is unstable angina?
plaque ruptures and must be treated quickly
67
How can you increase oxygen supply?
Increase oxygen flow
68
What are ways to decrease ischemia?
decrease HR, decrease contractility, decrease wall tension
69
Why would you want to use combo therapy with β-Adrenergic blocker for HTN?
↑Preload and tension so might want to use with something that ↓preload
70
BP=
CO x TPR
71
How do you decrease BP?
Decreasing TPR
| and CO
72
How do you decrease TPR?
by directly vasodilating or decreasing sympathetic activity
73
How do you decrease CO?
by decreasing contractility and preload with decrease in venous tone with diuretics
74
How is preload decreased?
inhibit Na Cl pump so more will be excreted and they bring water with them which will decrease preload
75
How do Thiazides work?
LT treatment to reduce vascular resistance and reduce afterload
76
What is the dominant receptor that angiotension II works on?
AT1
77
What is the effect of activation of AT1 receptors?
vasoconstriction, aldosterone secretion and Na retention
78
When do you treat HTN?
>140/90
79
What is order of treatment for HTN?
lifestyle modifications, then if uncomplicated Diuretics or Beta blockers
80
What anti HTN for diabetics?
ACE inhibitors and ARBS
81
What is good tx for pts with arrhythmias and fibrillation?
beta blockers and Ca antagonists (not DHP)
82
What should you do if no response or troublesome SE to anti-HTN med?
subsutitie to different class
83
What should you do if no response but well tolerated to anti-HTN med?
Add second agent from different class (diuretic)
84
For an AA woman 3 mo pregnant with type 1 diabetes w/ BP 160/90 and HR 50 bpm. What is the best tx option?
ARB (losartan) or ACE inhibitor (captopril)
85
For white male with hx MI with angina upon exercising and BP 160/90 and HR 75 bpm. What is the best tx option?
Beta blockers (propanolol)
86
For white male w/ hx LVH and BP 160/90 and HR 75 bpm. What is the best tx option?
ACE inhibitors (Captopril)
87
What tachy needs to be treated?
symptomatic or potentially life threatening
88
Whats happening at phase 0 of ventricular AP?
opening Na channels moving in
| depolarization, affects conduction velocity
89
Whats happening at phase 2 of ventricular AP?
Ca going in and K going out
depolarizing
affects AP duration
90
Whats happening at phase 3 of ventricular AP?
More K flow out than Ca flow in
| repolarizing, affects AP
91
Whats happening at phase 4 of ventricular AP?
"pacemaker curent"
K out < Na + Ca in
If channels
affects heart rate (automaticity)
92
Whats does the slope of phase 0 tell you?
conduction velocity
if shallower of a slope its slower conduction
affects resting membrane potential
93
What is the time from the Na channel closing from the time it becomes activatable?
refractory period duration (usually the same as the refractory period duration)
94
What channels affect pacemaker cells?
only Calcium
95
What current affects myocardium cells?
Large Na current initiates the AP but not in SA and AV nodes
96
What does the PR interval tell us?
conduction time from atrium to apical ventricular myocardium
97
What does QRS duration tell us?
time needed for all ventricular myocardium to be activated
98
what is ventricular flutter
organized, regular, 180-350
99
What are causes of tachycardias?
ectopic pacemaker or reentry circuits, early after depolarization, delayed after depolar
100
What is ventricular fibrillation
disorganized, irregular >350
101
What happens in coronary heart disease?
Partial vessel occlusion → regional hypoxia (ischmia)
| Hypoxia → ↓ATP → ↓ Na+/K+ ATPase activity → ↓ depolarization → ↑refractory period
102
Where are reentry circuits more common?
in ventricle
103
What causes reentry circuit?
multiple conduction pathways, refractory tissue, conduction time>refractory period
104
What is concern for patients with A fib?
risk of blood clot formation in atria which can lead to strokes (but not every patient gets anticoags)
105
What is goal of frug therapy of arrhythmias?
dec automaticity, dec conduction velocity, inc QT duration
106
When do you use anticoag for patients with a fib?
if CHA2DS2-VASc score > or = 2
107
Which Class I antiarrhythmic drug has longest refractory period? shortest?
Longest =IC
| Shortest =IB
108
What are schedule I drugs?
LSD, heroin, marijuana
| high potential for abuse and no acceptable use ad therapeutic
109
What are schedule II drugs?
morphine, oxycodone, codeine, amphetamine, cocaine, barbiturates
high potential for abuse but have acceptable medical use
110
What are schedule III drugs?
codeine+acetaminophen, anabolic steroids
| less potential for abuse
111
What are schedule IV drugs?
benzos, tramadol
| low potential for abuse
112
What are schedule V drugs?
low potential for abuse OTC meds w/ codeine
113
How does tolerance occur?
major mech: changes in cell receptors
| minor mech: enhanced elimination
114
What do drugs of abuse target?
GABAergic interneurons
dopaminergic neurons in VTA
medium sipny GABAergic interneurons in NA
(activate mesolimbin dopamine reward pathway)
115
What are seizures by cocaine due to?
local anesthetic effects in CNS
116
What are seizures by amphetamines due to?
lowering of seizure threshold
117
What are the catecholamines?
epinephrine, NE, dopamine
118
What is isoproterenol?
selective B agonist used to stimulate the heart
119
What is DA?
transmitter in the CNS precursor for NE in post ganglionic sympathetic nerve terminals
120
What is epinephrine?
neuro horomone released from adrenal medulla
121
What is NE?
transmitter of postganglionic sympathetic neurons
122
What inhibits NE release?
PGE2 and NE feedback at presynaptic alpha 2 receptors
123
What enhances release of NE?
angiotensin II
124
What metabolizes catecholamines?
MAO and COMT
125
What is heart failure with reduced ejection fraction?
systolic dysfunction-problem of volume overload (big chamber) which increased LVEDV and decreased SV
126
What is heart failure with preserved ejection fraction?
diastolic dysfunction-pressure overload (thick wall), decreased SV and decreased LVEDV
127
What happens when the heart is under chronic stress signals?
changes from alpha MHC to beta MHC and decreased contractility and hypertrophies
128
What does CHF do to the starling curve?
pushes it down because it decreases SV and increases EDV to compensate (if too much becomes pulmonary edema)
129
What happens if chronic B1 receptor stimulation and chronic Ang II stimulation?
adverse remodeling
130
What is seuqence of tx for systolic CHF?
↓weight, ↓activity, stop smoking, ↓preload (and sodium intake)
If doesn't work then: ARNI or ACEI or ARB to dec BP, preload and afterload
Once stable on RAAS add Beta blocker (in slow fashion because dec contractility and calcium if too fast will get hypotension)
Then give diuretic to decrease preload
More severe-give aldosterone antagonist (protects against fibrosis) or digoxin in worst case
131
What is goal in tc of CHF?
decrease preload, decrease afterload and decrease contractility
132
What is neprilysin?
degrades vasoactive peptides (ANP, BNP) which decreases renin secretion, increases vasodilation and also targets bardykinin (cough)
133
What does sacubitril get decomposed to?
LBQ657 the active compound of neprilysin
134
What are the K+ wasting diuretics?
Loop diuretics and Thiazide diuretics
135
When do you use diuretics?
edematous states
| HTN
136
What diuretic is best for edematous states?
loop diuretics
137
What are K+ sparing diuretics?
ENaC Inhibitors and Aldosterone antagonists
138
What is first drug of choice for HTN?
HCTZ
139
What is the main determinant of extracellular fluid volume?
Sodium
140
What are most diuretics aimed at?
decrease ECFV by increasing Na excretion
141
What are the compensatory mechanisms that occur as effect of diuretics?
increase sympathetic activity, increase renin-angiotensin-aldosterone activity, increase ADH, decrease ANP
142
What does carbonic anhydrase do in the proximal tubule?
breaks down carbonic acid into CO2 and water at luminal surface
