CVS Flashcards
1
Q
what are the 4 types of CVD?
A
- coronary heart disease
- strokes & transient ischaemic attacks
- peripheral arterial disease
- aortic disease
2
Q
what is primary prevention?
A
strategies that identify & alter modifiable risks to reduce incidence in disease-free pop.
3
Q
what is secondary prevention?
A
strategies that target individuals w/ established disease, usually have already had an event
4
Q
what is risk stratification?
A
• strategies used in primary care to identify potential patients
• estimate regularly >40s
• full formal assessment when risk 10% or higher
• use Q-risk
5
Q
what is coronary heart disease?
A
when arteries become narrowed by an atheroma
6
Q
what is acute coronary heart syndrome?
A
- when rupture/erosion of atherosclerotic plaque & subsequent thrombus formation
- thrombus because of platelet aggregation under high stress
7
Q
what is an ischaemic stroke/transient ischaemic attack?
A
when blockage because blood clot lodge in vessel narrowed by atheroma
8
Q
what is peripheral arterial disease?
A
- when build up of fatty deposits in arteries & restrict blood flow to leg muscles
- cause intermittent tiredness = claudication
9
Q
what treatments are required for arrhythmias?
A
- to control heart rhythm & rate to prevent cardiac arrest
- prophylactic to prevent stroke
10
Q
what is different in treatment of AF compared to treating arrhythmias?
A
- stagnation of blood in atria & incomplete ventricular emptying = clot formation
- strokes affect larger part of the brain & more likely fatal/leave bed ridden
- antiplatelets less effective = use anticoagulants
11
Q
what are 3 examples of ACS?
A
- unstable angina
- NSTEMI
- STEMI
12
Q
what is unstable angina?
A
- partial/transiently obstructive thrombus
- ischaemia, no necrosis
13
Q
what is an NSTEMI?
A
- partial/transiently obstructive thrombus
- ischaemia w/ necrosis
- partial thickness damage
14
Q
what is a STEMI?
A
- complete obstruction by intracoronary thrombus
- ischaemia w/ necrosis
- full thickness damage
15
Q
what are some symptoms of ACS?
A
- chest pain & pain in other parts
- sweating
- SOB
- lightheaded & dizzy
- nausea & vomiting
- anxiety & panic
- coughing & wheezing
16
Q
angina can be exacerbated and alleviated by?
A
- worse after food, cold winds, exercise, stress
- better after GTN, rest
17
Q
what are some ACS symptoms only found in women?
A
- heartburn
- cold sweats
18
Q
what are some ACS red flags?
A
- chest pain >15-20 mins
- recent onset unstable angina
- unresponsive GTN, w/ nausea, vomiting & sweating
19
Q
what are the differences between electrocardiograms taken for ACS conditions?
A
[ unstable angina & NSTEMI ]
- ECG can be normal
- may see ST depression/T-wave inversion
- no ST elevation
[ STEMI ]
- elevation ST
20
Q
what is cardiac troponin & what levels are considered?
A
- biological marker of cardiac muscle death
- normal = <14 ng/L
- if >14 ng/L = myocardial damage/necrosis
- if elevate 1st sample, repeat >3hrs later & rise >7 ng/L is likely MI
21
Q
what are some differential diagnosis for ACS?
A
- acid reflux
- pulmonary embolism
- anaemia
22
Q
what is treatment for angina for symptom relief?
A
[ 1st line ] - GTN spray
[ 2nd line ] - GTN sublingual spray
23
Q
what is treatment for angina for symptom prevention?
A
[ 1st line ] - BB or CCB
- if persist - BB + CCB
- if CI BB & CCB = add 2nd agent
[2nd line ] - long-acting nitrate/ Ivabradine/ Nicorandil
24
Q
what is treatment for angina for 2ndary prevention?
A
- aspirin
- statin
- ACEi
- hypertension treatment & lifestyle advice
25
what is used as initial management to treat unstable angina & NSTEMI?
- aspirin
- ticagrelor/ clopidogrel/ prasugrel
- LMWH = enoxaparin/ fondaparinux
[ to consider ] - O2 therapy, pain management, anti-sickness, hyperglycaemia
26
what is used as 2ndary prevention to treat unstable angina & NSTEMI?
- aspirin
- ticagrelor/ clopidogrel/ prasugrel
- ACEi
- statin
[ to consider ] - GTN spray for prophylaxis, hypertension treatment & lifestyle advice
27
what are the 3 types of circulation?
- systemic
- pulmonary
- coronary
28
describe the steps of haemodynamic control?
- ventricular filling = AV valves open & aortic valves closed
- ventricular systole = AV valves closed & aortic valves open
- early diastole = AV valves open & aortic valves closed
29
what parts of the heart are involved in electrical flow?
- sino atrial node = sends signal to ventricular cardiac myocytes in AV node (auto stim.)
- bundle of HIS = collect & carry signal to R&L ventricles
- Purkinge fibres = specialised myocardium for electrical conduction to cardiac myocytes
- fibrous mid line = no electrical conduction
30
what are the key features of the heart?
- auto-rhythmicity
- excitability
- conductivity
- contractility
31
what are the sinus rhythms?
- P to Q = atria systole
- Q to T = ventricular systole
- P-wave = atria depolarisation
- QRS complex = ventricle depolarisation
- T-wave = ventricle repolarisation
32
what is the equation for blood pressure?
BP = CO x PR
BP = HR x SV x PR
33
what is the process of autoregulation?
decrease O2 :
- increase CO2/K+/H+; increase lactic acid; increase histamine and body temp.
- stimulate endothelial cells release endothelin & platelets secretions & prostaglandins ( NO release in dilation)
- vasoconstriction pre capillary sphincters
34
what is the process of neural regulation?
via baroflex mechanisms
- baroreceptors in aorta send signal CV centre in brain = control vagus nerve
- brain send signal = change cardiac activity
- change heart contraction, HR & CO
35
what is the process of hormonal regulation w/ low BP?
- release renin = angiotensinogen to angiotensin I
- release ACE = angiotensin I to angiotensin II
- angiotensin II = potent vasoconstrictor & stimulate release aldosterone from adrenal cortex
36
what factors are affected by hormonal regulation?
- Na+ reabsorption
- osmotic pressure
- H2O reabsorption
- intravascular volume
- venous return
- CO
37
what is the process of hormonal regulation w/ high BP?
- stop release renin = block conversion angiotensinogen & no aldosterone release
38
what effect has erythropoietin w/ low BP?
- low O2 = trigger EPO release
- stimulate red bone marrow to produce RBC = increase O2 transport
- EPO is a vasoconstrictor = blood viscosity, resistance and pressure
39
what effect do catecholamines have w/ low BP?
- release by adrenal medulla
- vasoconstriction = increase HR & force of contraction
40
what effect do ADH and AUP w/ low BP?
- ADH secreted by hypothalamus & transporter to posterior pituitary = store until nervous stimuli
- ADH signal kidney reabsorb H2O & increase fluid level = constrict peripheral vessels & restore blood volume and pressure
41
what effect does ANP/ANH have w/ high BP?
- extreme stretching cardiac cells trigger ANP release; secreted atria cells
- natriuretic hormones = angiotensin II antagonists & promote Na+/H2O loss from kidneys; suppress renin, aldosterone & ADH release
- promote fluid loss = decrease blood volume & BP
42
what kind of information does the pulse give?
- heartbeat rhythm & heartbeat contraction; pulsatile volume and strength
- regular; regular irregular; irregular irregular
- weak, faint, strong and bounding
43
how is blood pressure measured?
- relaxed, temperate setting w/ person seated, arm outstretched and supported
- use both arms if significant difference > 15mmHg & use higher side for readings
- in-clinic > 140/90 = take other reading; if different again, take 3rd reading & record lower 2nd & 3rd
- 140/90 to 180/20; offer ABPM/HBPM
- BP > 180/20 = urgent treatment
44
what are some extra tests used for hypertension diagnosis?
assess for target organ damage
- haematuria & HbA1C for diabetes
- urine albumin:creatinine & examine fundi
- electrolytes, creatinine & eGFR for chronic kidney disease
- 12-lead ECG for left ventricular hypertrophic & assess CVD-risk w/ Q-risk
45
what should the patient be informed of when diagnosed for hypertension?
- absolute CVD risk & benefits/harms intervention in 10-year period
- present absolute event risk numerically
- use diagrams & text
46
what are the steps of full history taking?
- introduction
- presenting complaint
- history of presenting complaint
- past medical/surgical history
- family history
- social history
- drug history
- systems review
47
what should be involved in social history?
- alcohol intake
- tobacco use
- recreational drug use
- employment history
- home situation
- travel history
48
what is involved in drug history?
- confirm name & dose = prescribed, OTC, vitamins, supplements & herbal medicines
- borrowed, recently started, stopped & changed
- compliance
- allergies
49
what are the different types of metabolisers?
- poor metabolisers
- normal metabolisers
- rapid metabolisers
- ultra-rapid metabolisers
50
what are some BBs side effects?
- fatigue
- cold extremities
- low pulse
51
what are factors that affect ADME?
[ genetic polymorphisms ]
- SNPs
- tandem repeats
- micro-satellites
- insertions & deletions
52
what are some drugs to be avoided with ACEi?
[ Aliskiren ]
- risk of renal impairment
[ Allopurinol ]
- risk hypersensitivity & haematological reactions
[ Azathioprine ]
- risk anaemia & leukopenia
[ Everolimus ]
- increased risk angioedema
53
what are some adverse effects of thiazide-like diuretics?
- postural hypotension
- hyperglycaemia
- hypokalaemia
- cardiac arrhythmias
- metabolic alkalosis
- dehydration
- hyponatremia
54
what are some contraindications of thiazide-like diuretics?
- refractory hypokalaemia
- hyponatraemia
- hypercalcaemia
- Addison’s disease
- pregnant women
- severe liver & renal impairment
55
what are some contraindications of CCBs?
- uncontrolled HF
- AV block
- unstable angina/recent MI
- hepatic & renal impairment
- pregnant/breastfeeding
- grapefruit
56
what are ACE inhibitors?
- target production angiotensin II = act on AT1 receptor; adrenergic innervations; release ADH
- block vasoconstriction & aldosterone release
57
what are the effects of ACEi?
[ arterial & venous vasodilation ]
- decrease arterial & venous pressure
- decrease ventricular preload & after load
[ decrease blood volume ]
- natriuresis
- diuresis
- down regulation sympathetic activity & suppression hypertrophy
58
what are some rare adverse effects of ACEi?
- hyperkalaemia = aldosterone
- taste disturbance = zinc in ACEi
- hypotension
- renal impairment
- angioedema
59
what are some clinical considerations with ACEi?
- cough = class effect
- hypotension = combine low-dose diuretics
[ dehydration ] = suspend
- diarrhoea & vomiting
- postural hypotension
- acute kidney disease
60
what are some renal risk assessments for ACEi?
- beneficial chronic kidney failure & hypertension
- monitor serum creatinine, electrolytes & eGFR
- periodically assess renal function
- discontinue bilateral renal artery stenosis
61
when are ACEi avoided?
- 55 or less
- caribbean/black african origin = decrease response renin-dependent BP regulation
- pregnant & breastfeeding
62
what are some adverse effects of ARBs?
- hyperkalaemia = aldosterone
- renal impairment
63
how do BBs work?
- block sympathetic effect
- adrenaline bind B-1 receptor & increase heart activity = BB block receptor
- prolong PR interval = decrease SA & AV nodes automaticity
64
what are the effects of BBs?
[ cardiac ]
- contractility
- relaxation rate
- HR & conduction velocity
[ vascular ]
- mild smooth muscle contraction
65
what are some adverse effects of BBs?
- bradycardia
- bronchoconstriction
- cardiac depression
- hypoglycaemia
66
what are some cautions w/ BBs?
- pre-existent bradycardia
- conduction defect
- HF
- cardio-selective CCBs
67
how do CCBs work?
- block Ca2+ channels
- reduce contraction force & smooth muscle contraction
68
what is the effect of dihydropyridines and non-dihydropyridines?
[ dihydropyridines ] = amlodipine
- vascular effect
- vascular smooth muscle relaxation
[ non-dihydropyridines ] = verapamil & diltiazem
- cardiac effect
- reduce contraction force & HR
- reduce conduction velocity
69
what are some side effects of dihydropyridines?
[ oedema ]
- CCB dilate arteries but veins constricted
- capillary overload forces fluid into surrounding tissue
[ reflex tachycardia ]
- baroreceptor reflex
70
what are some side effects of non-dihydropyridines?
- bradycardia
- AV node block = impaired electrical conduction; Ca2+ channels located in electrical nodes
- contractility = cardiac depression
71
what are some clinical considerations for thiazide-like diuretics?
- potassium supplements
- potassium-sparing diuretics
- avoid ACEi = hyperkalaemia
72
how do thiazide-like diuretics work?
- moderately powerful = indapamide
- block Na+/Cl- symporter of early DCT = inhibit Na+ active reabsorption & Cl- transport = H2O reabsorption
- promote natriuresis & diuresis
73
how do aldosterone receptor antagonists work?
- antagonise mineral corticoid receptors
- prevent insertion Na+/K+ ATPase pumps & ENAC channels in late DCT & CD
- spironolactone & eplerenone
74
how do Na+ channel blockers work?
- block apical ENAC in late DCT & CD
- decrease influx Na+
- Na+ not retained at expense K+
- amiloride & triamterene
75
what are the 2 states of solid?
[ crystalline ]
- polymorphous; solvates & hydrates; co-crystals
- molecules packed in defined order
- cool slowly to below melting point & between melt and freeze
[ amorphous ]
- unstructured ice
- molecules packed in random order
- rapid solidification/precipitation & glassy and rubbery
- moisture sensitive
76
what is polymorphism?
- different molecular arrangements in crystal lattice
- difference = molecule orientation/conformation in lattice sites
77
how is x-ray diffraction used to differentiate between crystals?
- characteristic pattern of diffraction angles & intensity diffracted beam = planes of crystal
- crystalline = high intensity & narrow peaks
- amorphous = low intensity & broad peaks
- polymorphic = median intensity & narrow peaks
78
how does hydration occur in crystal lattices?
- small molecular size H2O
- multi-directional H-bonding capability
79
how is the salt form better than other crystal forms?
- increase solubility
- increase dissolution
80
what is a co-crystal?
- 2 or more molecules in same crystal lattice in definite stoichiometric ratio
- not based ionic bonds
= sildenafil & aspirin
81
what are some primary powder properties and their effects?
[ particle size ] & [ shape ]
- content uniformity
- flow & mixing
[ surface area ]
- dissolution rate
82
what are some secondary powder properties and their effects?
[ density ]
- tablet/capsule size
[ porosity ]
- compressibility
- permeability/H2O uptake
[ flowability ]
- content uniformity
[ compressibility ]
83
how are small & irregular particles measured?
- 3D size impractical
- only 1 dimension used
84
how is the surface area of irregular particles measured?
- Brunauer-Emmett-Teller theory (BET theory)
- powder filled into vacuum-sealed chamber
- small amounts N2 added & adsorb to powder surface until entire surface and pores covered
- pressure transducers sense gas amount adsorbed = used calculate SA
85
what are 4 equivalent diameters for sedentary particles?
- projected perimeter diameter & projected area diameter
- feret's diameter & martin's diameter
- sieve diameter
- diameter of equivalent volume/SA/mass sphere
86
what are 3 equivalent diameters for moving particles?
[ stoke's diameter ]
- sphere w/ same density & settling velocity as particle
[ aerodynamic diameter ]
- sphere w/ same density & terminal velocity in air/any relevant fluid as particle
[ hydrodynamic diameter ]
- sphere w/ same density & settling velocity that diffuses at same rate in liquid as particle
87
what are the different dimensions and types of particle shapes?
- 1D = acicular & rod-shaped
- 2D = flaky & dendritic
- 3D = porous, angular/irregular; spherical & rounded
88
how good is the flowability of each type of particle shape?
- spherical & rounded = good & easy mix
- acicular; rod-shaped & angular/irregular = tend interlock = increased mechanical strength
- flaky = cohesive effect because greater SA
89
what drugs often cause interactions?
[ problematic ]
- enzyme inducers & inhibitors
- PGP protein inducers/inhibitors & chelating agents
[ long half lives ]
[ overdose/underdose ]
- narrow therapeutic windows
- therapeutic drug monitoring
- critical medications
90
what are some resources used for drug interactions?
- BNF = paper, mobile & web app
- drug SPC
- Stockleys
91
what are some drugs that cause absorption issues?
- calcium-containing products = Adcal & Calchichew
- aluminium-containing antacids = Gaviscon & Peptac
- chelating agents = doxycycline, alendronic acid & levothyroxine
92
what are some drugs that affect distribution?
- sodium valproate
- phenobarbital
- phenytoin
- carbamazepine
- warfarin
93
what are the steps of phase 2 in metabolism?
- conjugation
- acetylation
- sulfation
94
what are some metabolism inducers?
- carbamazepine
- rifampicin
- phenobarbitone
95
what are some metabolism inhibitors?
- sodium valproate
- ketoconazole
- erythromycin/clarithromycin
96
how is excretion affected by drug interactions?
- via glomerular filtration & active tubular secretion
- site competition = interactions when eliminated via same active transport mechanism in PT
- elim. w/ low affinity to transport protein = drug accumulation
- urine pH can also affect reabsorption
97
what are some PGP inducers/inhibitors?
- apixaban
- colchicine
- ciclosporin
- dabigatran
- digoxin
- tacrolimus
98
what affects warfarin effect?
[ increase ]
- grapefruit/pomegranate/cranberry
- large acute alcohol
[ decrease ]
- green leafy vegetables/egg yolks/chickpeas
- chronic heavy alcohol
99
what are MAOI?
- monoamine oxidase inhibitors
- antidepressant w/ frequent interactions
100
what should be avoided w/ MAOI?
- tyramine-rich & dopa-rich foods
= mature cheese; salami & alcohol
- only fresh food products
- continue 2-3 weeks after stopping = long half life
101
how does grapefruit juice affect ADME?
- inhibit CYP 3A4 isoenzyme
- statins; CCBs & antibiotics
102
what are patients at higher risk of interactions?
- elderly = less renal & liver function
- children = underdeveloped metabolising systems
- w/ co-morbidities
- polypharmacy
103
what is heart failure diagnosis based on?
- signs & symptoms
- patient history
- blood levels NT-proBNP
- ECG
- exercise tolerance test
- transthoracic echocardiography
104
what are some other tests used to confirm HF?
- full bloods
- thyroid function tests
- chest x-ray
- peak flow test
105
what is HF?
- increased pressure in heart & inadequate cardiac output
- due to left ventricular & myocyte dysfunction from MI
- progressive & no cure
106
what are the features of HF?
[ fatigue ]
- low CO = low O2
[ oedema ]
- pulmonary & peripheral
- fluid retention; increase heart pressure affect pulmonary vessels & failing kidneys
[ breathlessness ]
- dyspnoea & orthopnea
- lying down redistribute oedema on lungs
- patient sleep w/ multiple pillows (3+)
107
what is NT-proBNP and its function?
- released response pressure changes in heart
- less 400ng/L = less likely HF
- more 2000ng/L = poor prognosis
- used monitor progress HF
108
what may decrease levels of NT-proBNP?
- obesity
- african-caribbean
- current treatment ACEi/ARBs/mineral corticoid receptor antagonists
109
what may increase levels of NT-proBNP?
- age > 70
- LV hypertrophy
- renal dysfunction
- sepsis
- COPD
- diabetes
- ischaemia
110
how is severity of HF graded?
- NYHA functional classification system
- symptoms alone & show effect functional ability & QoL
111
what is preserved EF?
- preserved Ejection Fraction
= more 40%
- preserving EF = slow deterioration
112
how is HF with preserved EF treated?
- loop diuretic & titrate
- relieve congestive symptoms & fluid retention
- 1st line = ACEi & BB
- add in = mineralcorticoid receptor antagonists
113
what is the future treatment for HF?
- SGLT2 inhibitors = dapaglifozin/empaglifozin
- symptomatic HF w/ reduced EF
[ only add optimised care by HF specialist ]
- ACEi/ARB & BB & MRA
- Entresto & BB & MRA
114
what is used to control symptoms in palliative care?
[ breathlessness ]
- repeated small dose opioids
- oramorph
[ pain ]
- opioids PO or SC
- morphine/oxycodone
[ anxiety ]
- midazolam = help agitation
[ N&V ]
- depends trust & other meds = cyclizine
[ secretions ]
- prevent death rattle = hyoscine hydrobromide
115
what is palliative care?
- optimise QoL & reduce suffering in patients w/ life-threatening conditions
- symptom control = make comfortable
- honour patient wishes & family informed trajectory
116
how is acute/decomposed HF treated in 2ndary care?
- IV diuretics = bolus/infusions furosemide
- risk ototoxicity & renal impairment
- stable 48 hours = stop IV & re-start meds
- monitor renal function, electrolytes, HR & BP
117
what is some lifestyle advice for HF patients?
- regular exercise & physically active
- sleep & careful hidden salts
- balanced diet & health weight
- lower alcohol & smoking
- eligible flu vaccine
118
what is a cardiac rehab programme for HF patients?
- personalised, exercise-based programme for stable HF
- exercise training = increase tolerance & QoL
- include psychological & education component
119
how is HF treatment monitored?
- assess functional capacity; fluid status; cardiac rhythms
- cognitive & nutritive status
- assess renal function & other Us and Es
- monitor NT-proBNP
- teach patient recognise symptoms change & alert HP
120
what if optimal drug management doesn't work for a HF patient?
- w/ severe refractory symptoms = cardiac transplant
- if older & co-morbidities = unlikely consider
- referral specialist centre & waiting list
- complications = life-long immunosuppression; risk rejection & graft failure
121
what is the CVS disease continuum?
- endothelial dysfunction
- atherosclerosis
- ischaemia
- coronary artery disease
- thrombosis & lesion rupture
- myocardial infarction
- reduced contraction
- ventricular dilation & remodelling
- heart failure
- death
122
what can affect endothelial dysfunction?
- hypertension
- dyslipidemia
- diabetes mellitus
- smoking
123
how does ischaemia occur?
- thicken internal surface arteries & atherosclerotic lesions
- block & affect O2 supply heart muscles
124
what are the troponin levels for angina, NSTEMI & STEMI?
stable & unstable = no change troponin
NSTEMI = changes troponin
STEMI = rise troponin
125
how does NO cause vasodilation?
- endothelial cells release NO
- NO stim. cytoplasmic guanylyl cyclase
- elevate intracellular cGMP
- activate protein kinase G
- smooth muscle relaxation = vasodilation
- PDE isoform breaks down cGMP
126
what are the features of systemic circulation?
- venous dilation > arterial dilation
- decreased venous pressure
- decreased arterial pressure = small effect
127
what are the features of cardiac circulation?
- reduced preload and afterload = decreased wall stress
- decreased O2 demand
128
what are the features of coronary circulation?
- prevent/reverse vasospasm
- vasodilation epicardial vessels
- improve subendocardial perfusion
- increased O2 delivery
129
what are nitrates used for and what types are there?
- acute attacks/ preventative measures
- direct = nitroglycerin & sodium nitroprusside
- organic = isosorbide dinitrate & mononitrate
130
what are some conditions that involve thrombosis in the veins?
- deep vein thrombosis
- varicose vein
131
what are the 2nd line antianginal drugs?
- IF current inhibitors = ivabradine
- Class ID sodium-channel blocker = ranolazine
- Potassium channel activator = nicorandil
132
how does ivabradine work?
- selectively block hyperpolarization-activated cyclic nucleotide-gated channels in SA nodes
- lower heart rate without affecting contractility of cardiac muscle
133
how does ranolazine work?
- block late inward sodium currents in phase 2 ventricular action potentials
134
how does nicorandil work?
- activate ATP-sensitive K+ channels
- enhance K+ efflux & hyperpolarization vascular smooth muscle cells
- reduce Ca2+ entry & reduce cardiac contraction
135
what are the 3 phases of haemostasis?
- vascular spasm
- platelet activation
- coagulation
136
how does a vascular spasm work?
- pain reflux = constriction vascular smooth muscle
- trigger clotting factors needed & directed to injury site
137
how does platelet activation work?
- endothelial damage & exposed collagen
- platelets stick to exposed collagen
- platelets stimulate ADP; thromboxane A2 & serotonin
- von willebrand factor = bridge w/ collagen exposed in damaged blood vessels & glycoprotein receptors GPIIb/IIIa expressed in activated platelets = stabilise collagen-platelet adhesion
- glycoprotein receptor bind fibrinogen & form platelet-fibrin plug
138
how does coagulation work?
- coagulation factors in liver (ex: vitamin k) and biosynthesis clotting factors (ex: plasma proteins I to XIII)
- X-A (prothrombin activator) ⇒ activate X (prothrombin)
- prothrombin converted to thrombin & fibrinogen (soluble) = fibrin (insoluble) = fibrin mesh
139
what are the 2 steps of clot & vessel healing?
- clot retraction w/ vessel repair
- fibrinolysis
140
how does fibrinolysis work?
- plasminogen = plasma protein trapped in clot
- converted plasmin & digested to fibrin
141
how does clot retraction & vessel repair work?
- actin & myosin in platelets contract and pull fibrin strands
- platelet-derived growth factor stimulate smooth muscle & fibroblast division
- vascular endothelial growth factors rebuild endothelial lining = multiplying endothelial cells
142
what are the 3 types of antithrombotic drugs and their functions?
- anticoagulants = prevent thrombus formation
- antiplatelets = prevent platelet aggregation
- fibrinolytics = clot retraction
143
what are the 2 types of oral anticoagulants?
- vitamin K antagonist = warfarin
[ direct oral anticoagulant ]
- reversible factor Xa inhibitor = apixaban; edoxaban & rivaroxaban
- reversible thrombin inhibitor = dabigatran
144
what are fibrinolytics & their functions?
- plasminogen activators = digest fibrin mesh of clot
- plasminogen = plasma protein trapped in clot
- activated by tissue plasminogen activator = plasmin & digest fibrin
145
what class is aspirin and its function?
- COX-inhibitor
- low dose irreversibly inhibit thromboxane in platelets = decrease platelet aggregation
- in endothelial cells, aspirin inhibit prostaglandins = increase platelet aggregation
146
what are glycoprotein IIb/IIIa inhibitors and 2 example types?
- prevent platelet aggregation by block binding fibrinogen to receptor on platelet
- abciximab
- eptifibatide & tirofiban
- specialists only & administer i.v. hospital & high risk bleeding
147
what is the function of abciximab?
- monoclonal antibody bind to glycoprotein IIb/IIIa receptors & other related sites
- adjunct HUF & aspirin for prevention ischaemic complications = high risk pts percutaneous transluminal coronary intervention
- use once only = risk thrombocytopenia
148
what is the function of eptifibatide and tirofiban?
- inhibit glycoprotein IIb/ IIIa receptors
- use prevent early MI in pts w/ unstable angina/ NSTEMI
149
what are the 2 example types of tissue plasminogen activators?
- streptokinase
- alteplase; reteplase & tenectplase
150
what is the features of streptokinase?
- natural bacterial protein
- limited use/rare use
- pts develop antibodies & inactive streptokinase
151
what are the features of alteplase, reteplase & tenectplase?
- synthetic recombinant
- highly-selective fibrin-bound plasminogen = clot selective
- reteplase & tenectplase = longer half-life alteplase
152
what are some adverse effects of tissue plasminogen activators?
- allergic reactions
- haemorrhage
- hypotension
153
which drugs does warfarin interact with?
- macrolide antibiotics; azole antifungals; H2 receptor antagonists = breakdown warfarin
- NSAIDs; broad-spectrum antibiotics = kill gut flora and vitK synthesis = potentiate warfarin
154
what are some adverse effects of warfarin?
- bleeding
- skin necrosis
155
what is the features and function of warfarin?
- slow onset action & preferred venous thromboembolic disorders
- inhibit vitk-dependent protein C = natural anticoagulant = procoagulant effects before anticoagulant effects
- vitK in excess overcome warfarin binding reductase enzyme = manage warfarin overdose w/ vitK
156
how does warfarin work?
- warfarin inhibit reduction vitK = decrease activated clotting factors in blood = competitive antagonist)
- unmodified coagulation factors II, VII, IX and X = y-carboxylation = activated
- y-carboxylation need reduced vitamin K = converted oxidised vitamin K
- vitamin K reductase = oxidised vitK = reduced vitK
157
what are functions of oral anticoagulants?
[ apixaban; edoxaban; rivaroxaban ]
- direct & reversible inhibitors factor Xa
- inhibition factor Xa prevent thrombin generation & thrombus development
[ dabigatran ]
- reversible inhibitor of free thrombin; fibrin-bound thrombin & thrombin-induced platelet aggregation
158
what is the function of unfractionated heparin and LMWH?
- HUF & LMWHs bind anti-thrombin III = inhibit thrombin activity + block thrombin-mediated platelet activation
- inhibit factor Xa = compliment anticoagulant effect
- rapid onset action
159
what is the differences between HUF and LMWH?
- HUF = non-spec. plasma protein & tissue binding
- LMWHs = no non-spec. binding w/ LMWHs = predictable dose-dependent response = offer better-sustained clinical effect
160
what are the adverse effects of HUF & LMWH?
- haemorrhage
- heparin-induced thrombocytopenia/ low platelet
- hyperkalaemia
161
how is haemorrhage stopped for HUF & LMWH?
- withdraw HUF/ LMWH
- if rapid reversal of heparin effects needed = protamine sulfate
- spec. antidote = neutralise/inactivate heparin but only partially reverse effect LMWH
162
how is heparin-induced thrombocytopenia stopped for HUF & LMWH?
- immune-mediated & complicated by thrombosis
- signs = 30% reduction platelet count, thrombosis & skin allergy
- use alternative coagulant = danaparoid
163
how is hyperkalaemia stopped for HUF & LMWH?
- inhibition aldosterone secretion result
- diabetes mellitus; chronic renal failure; acidosis; raised plasma K+ & K+ sparing drugs = more susceptible
- risk increase duration therapy
164
what is the function of clopidogrel & prasugrel?
- irreversibly inhibit ADP binding to P2Y12 receptors
- reduce platelet aggregation
- use prevention recurrence arterial ischaemic disease & ACS
- combine aspirin enhance outcome & reduce CV risk but increase haemorrhage risk
165
what is the function of ticagrelor?
- directly act P2Y12 receptors & reversibly inhibit
- reduces ADP-mediated platelet aggregation
- non-competitive inhibitor = alternative clopidogrel & prasugrel
166
how do ADP-receptor antagonists work?
- activated platelets stimulate ADP release
- act P2Y12 receptors in platelets
- activate +ve feedback = more platelet plug formation
167
what are the types of parenteral anticoagulants?
- HUF & LMWH = dalteparin; enoxaparin & tinzaparin
- heparinoids = danaparoid
- argatroban
- hirudins = bivalirudin
- heparin flushes
- epoprostenol
- fondaparinux
168
what are the functions of heparinoids & argatroban?
[ heparinoids ]
- high affinity for Xa
- i.v. use
[ argatroban ]
- direct thrombin inhibitor
- i.v. use
169
what is the function of hirudins & heparin flushes?
[ hirudins ]
- thrombin inhibitor licensed for unstable angina/ NSTEMI & anticoagulant for pts undergoing percutaneous coronary intervention (PCT)
[ heparin flushes ]
- maintaining the patency artery & venous catheters
170
what is the function of epoprostenol?
- prostacyclin
- inhibit platelet aggregation in renal dialysis when heparins unsuitable/CI
- epoprostenol = potent vasodilator
171
what is the function of fondaparinux?
- synthetic polysaccharide
- selective factor Xa inhibitor
- similar efficacy LMWH & rapid onset action
- 1st line ACS
172
do CCB block Ca2+ channels?
- no, they just stop influx of Ca2+
- bind to specific and different allosteric sites
173
what are the 3 classes of drugs used to treat hyperlipidaemia?
- HMG-CoA reductase inhibitors = statins
- cholesterol absorption inhibitors = ezetimibe
- fibrates = fenofibrate & gemfibrozil
- anion exchange resins = colestyramine
174
how do statins lower plasma cholesterol levels?
- inhibit cholesterol biosynthesis
- inhibit HMG-CoA reductase = block access to active site
- to compensate, liver recruit more LDL from blood
175
what are lipids?
- free fatty acids, cholesterol & triglycerides
- synthesised in cell = endogenous
- derived from dietary fat = exogenous
176
what is cholesterol?
- makes cell membrane & moderate fluidity
- cell growth & viability
- precursor steroid hormones, vitD and bile salts
177
what are triglycerides?
supply energy to muscle & other tissues
178
what is HMG-CoA reductase?
- membrane-bound enzyme
- catalyses rate-limiting step in sterol biosynthesis
- primary target hypercholesterolemic drug therapy
179
what is the process of cholesterol absorption into the blood?
- enters micellar membrane in intestine
- absorbed & transported to liver & mix w. hepatic cholesterol
180
how is cholesterol absorbed from micelles into intestinal wall?
- through Niemann-Pick C1 Like 1 protein on enterocyte plasma membrane
- bile emulsify dietary lipids & facilitate absorption
- bile salts recycle via hepatic portal vein
181
what is the Niemann-Pick C1 Like 1 protein?
- gateway for dietary cholesterol enter into circulation
- target for modulating cholesterol level
182
what are lipoproteins?
- complex particles mobilise cholesterol & TGs
- central core = cholesterol esters = hydrophobic
- TGs surrounded by free chol & phospholipids = amphophilic
183
what are the functions of apolipoproteins?
- serve structural role
- act as ligand for lipoprotein receptors
- guide formation lipoproteins
- serve activators/inhibitors of enzymes involved in metabolism of lipoproteins
184
what's the difference between LDLs and HDLs?
- LDL = higher lipids at the core
- HDL = low lipids at the core
185
what are the 4 types of lipoproteins?
- chylomicrons
- chylomicron remnants
- very low density lipoproteins
- intermediate-density lipoproteins
186
what are chylomicrons?
- large triglyceride-rich particles made by intestine
- involve in transport of dietary triglycerides & cholesterol to peripheral tissues & liver
187
what are chylomicron remnants & VLDLs?
[ remnants ]
- removal of TGs by peripheral tissues
- becomes smaller particle
[ VLDLs ]
- produced by liver
- TGs rich
188
what are IDLs?
- removal TGs from VLDLs by muscle & adipose tissue
- form enriched in cholesterol
189
what are LDLs?
- derived VLDLs & IDLS & enriched in cholesterol
- carries majority chol in circulation
- contains Apo B-100 molecule
- high Apo B-100 = high risk atherosclerosis
190
what are high number of small LDLs associated with?
- hypertriglyceridemia
- low HDL levels
- obesity - type 2 diabetes
- infectious & inflammatory states
191
what are HDLs?
- cholesterol & phospholipids
- Apo A-1 = core structural protein
- high Apo A-1 levels = low risk atherosclerosis
192
how are HDL particles important?
- role in reverse cholesterol transport from peripheral tissues to liver
- potential mechanism HDL = anti-atherogenic
193
what are the 4 pharmacological options for lipid lowering?
- cholesterol synthesis inhibition
- intestinal absorption
- lipoprotein lipase activity
- HDL
194
what are adverse reactions due to statins?
- GI disturbances
- skeletal muscle myopathy
- myalgia
- myositis w/ rhabdomyolysis
195
how do anion exchange resins work?
- bind with bile salts = insoluble complex
- lower intestinal cholesterol absorption
196
what are some issue with anion exchange resins?
- unpalatable & digestive problems
- interfere with fat-soluble nutrients & drugs
- limited use
197
how does ezetimibe work and what are some issues?
- block transport protein NPC1L1 in gut wall
- digestive problems; myalgia; fatigue & headache
198
what is thromboxane?
- potent vasoconstrictor & inducer platelet aggregation
- COX-1 convert from arachidonic acid = prostaglandin H2 = Thromboxane A2
199
what role does P2Y12 play in platelet aggregation?
- ADP bind P2Y12
- inhibit adenyl cyclase
- decrease intracellular cAMP
200
how are antiarrhythmic drugs classed?
- based on electrophysiological effect
- I = NA+ channel blockers =rapid depolarisation
- II = B-adrenergic blockers
- III = K+ channel blockers = repolarisation
- IV = CCB = plateau
201
how do K+ channel blockers work?
- block outflow K+
- prolong QT interval = prolong refractory period & AP duration
202
what are the 2 considerations before attempting retrosynthesis?
[ percent yield ]
- number of single steps minimised & simple
- yield each step maximised = avoid side products
[ type of synthesis ]
- linear synthesis
- convergent synthesis
203
why is convergent synthesis almost always the best choice?
- lower amount of steps
- shorter time & higher yields
- better carbon economy
204
what are synthons & synthetic equivalents?
- synthons = not real molecules = representation of separation charges
- SE = actual substrates for forward synthesis
205
what is the pathophysiology of atherosclerosis?
- endothelial dysfunction
- formation lipid layer/fatty streak in intima
- migration leukocytes & smooth muscle cells into vessel wall
- foam cell formation
- degradation extracellular matrix
206
what are the 3 types of familial hyperlipidaemia?
- combined hyperlipidaemia
- hypercholesterolaemia & polygenic hypercholesterolaemia = high chol. content
- hyperapobetalipoproteinemia = high levels apolipoprotein B
207
what is familial combined hyperlipidaemia?
- high levels LDL cholesterol & TGs
- young age
- high risk early coronary heart diseases
208
what are the three arrhythmias that are treated with anti-arrhythmic drugs?
- supraventricular arrhythmias
- both supraventricular & ventricular arrhythmias
- ventricular arrhythmias
209
what are the reasons for granulation?
- prevent segregation of constituents
- improve flow properties
- improve compaction properties & uniformity
- reduce toxic dust &caking of hygroscopic materials
- increase bulk density = reduce storage volume
210
what are the limitations of wet granulation?
- cost = labour, time, equipment, energy & space
- stability = moisture-sensitive & thermolabile
- loss of materials
- multiple processing steps
- incompatibilities = b.w formulation components
211
what are the steps of wet granulation?
- blend powder & add binder = sucrose/gelatin
- sieve moist mass
- dry the moist agglomerates
- sieve the dried granules = sized granules
212
what are the steps of dry granulation?
- compress blended powder
- mill the slug/tablet from compression chamber
- sieve the granules = sized granules
213
what are the limitations of dry granulation?
- high force/pressure involved in compaction
- greater chances generation dust & environmental contamination
