cvs Flashcards
1
Q
where does sympathetic nerves arise?
A
emerge from thoracic area of spine
2
Q
where does parasympathetic nerves arise?
A
from cranial nerves and lumbar sacral areas of spine
3
Q
length of pre and postsynaptic nerve for sympathetic nerves
A
pre: short
post: long
ganglion: inside sympathetic chain
4
Q
length of pre and postsynaptic nerve for parasympathetic nerves
A
pre: long
post: short
ganglion: in wall of organ/tissue
5
Q
explain somatic nerve
A
- supply skeletal muscle
- no ganglions
- voluntary control
6
Q
main neurotransmitters in ANS?
A
Ach and NE
7
Q
what organ/tissue in sympathetic pathway with no postsynaptic fibre?
A
adrenal gland
8
Q
what sympathetic pathway that include both Ach and NE
A
pathway to smooth mucle, cardiac cells and gland cells to contract
9
Q
functions of parasympathetic
A
- SLUDD (salivation, lacrimation, urination, digestion, defeacation)
- anabolic, conserves and stores energy
10
Q
functions of sympathetic
A
- fight or flight
- catabolic, mobilises energy, raise BP and body temperature, dilates airways etc
11
Q
non-adrenergic and non-cholinergic neurotransmitter
A
- nitric oxide
- serotonin
- ATP
- GABA
- dopamine
- purines
- neuropeptide
12
Q
Ach synthesis by
A
choline acetyltranferase
13
Q
hydrolysis of Ach by
A
acetylcholine esterase
14
Q
choline reuptake by
A
Na+ driven symport
15
Q
types of Ach receptors
A
- nicotinic (Nm and Nn)
- muscarinic ( M1, M2, M3)
16
Q
explain nicotinic receptors
A
- muscle-type and nerve-type
- cause membrane depolarization
- role in neuromuscular junction (skeletal) and ganglionic transmission (nerve)
17
Q
explain muscarinic M1
A
- in CNS, ganglia, gastric, parietal cells
- increase IP3, DAG (excitation)
- role in memory CNS, gastric acid secretion, GI motility
18
Q
explain muscarinic M2
A
- in cardiac conducting tissue and presynaptic terminals
- decrease CAMP (inhibition)
- role in cardiac, presynaptic and neural inhibition
19
Q
explain muscarinic M3
A
- exocrine gland, smooth muscle and blood vessels
- increase IP3, DAG (excitation)
- role in secretion, SM contraction, vasodilatation
20
Q
cholinoceptor agonists
A
- acetylcholine
- carbachol
- methacholine
- bethanechol
21
Q
cholinoceptor agonist that do not hydrolyse by AchE
A
bethanecol
22
Q
Nicotinic muscular type agonist
A
- Ach
- suxamethonium
- decamethonium
23
Q
nicotinic muscular type antagonist
A
- vecuronium
- pancuronium
24
Q
nicotinic nerve type agonist
A
- Ach
- nicotine
- epibatidine
25
nicotinic nerve type antagonist
- trimetaphan
| - hexamethonium
26
AchE can be block by
serine occlusion
27
products of hydrolysis of AchE are
- choline
- acetic acid
- regenerated enzyme
28
reuptake of NA is blocked by
- cocaine
| - tricyclic antidepressants
29
adrenoceptor B1
1. in heart, intestine, smooth muscle
2. increase cAMP
3. increase BP
30
adrenoceptor B2
1. In bronchial, vascular and uterine smooth muscle
2. bronchodilation, vasodilation, uterine SM
3. increase cAMP
31
adrenoceptor A1
1. postsynaptic
2. increase IP3, DAG
3. increase BP
4. cause vasoconstriction
32
adrenoceptor A2
1. presynaptic
| 2. decrease cAMP
33
a adrenoreceptors agonist specificity
noradrenaline > adrenaline > isoprenaline
34
a adrenoreceptors antagonist specificity
phentolamine
35
actions of NA terminated by when
1. reuptake into nerve terminal
2. dilution and diffusion from cleft and uptake at non-neuronal sites
3. metabolic transformation
36
enzymes important in biotransformation of cathecholamines
1. COMT (cathecol-0-methyl transferase)
| 2. MAO (monoamine oxidase)
37
b adrenoreceptors antagonist specificity
propanalol
38
Example of muscarinic receptors antagonist
Atropine (treat bradycardia)
| hyoscine
39
Indirect acting of cholinergic agonist
Action of cholinesterase inhibitors (inhibit Ach catabolism)
40
Example of muscarinic receptors agonist
1. pilocarpine (use as eye drop to treat glaucoma)
| 2. bethanechol
41
Two type of cholinergic agonist
1. Choline esters (Ach, bethanechol)
| 2. Alkaloids (pilocarpine)
42
What are the effects produced by muscarinic agonists?
Parasympathetic-like effects.
1. Smooth muscle (M1) - Increase GI peristaltic activity
2. Cardiovascular (M2) - Cardiac slowing, decrease c. output
3. Eye (M3) - Contraction of ciliary muscle
4. Secretions (M3) - Stimulation of exocrine glands, sweating, lacrimation, salivation and bronchial secretion.
43
what is glaucoma?
increase intraocular pressure due to increase aqueous fluid production and decreased its trabecular outflow.
44
Effects produced by muscarinic antagonists
Sympathetic-like effects
1. Smooth muscle (M1) - Bronchial, biliary & urinary tract SM relax. GI transit is inhibited
2. Cardiovascular (M2) - Tachycardia
3. Eye (M3) - Dilation of the pupil and relaxation of ciliary muscle
4. Secrettions (M3) - Inhibition of secretions; dry mouth, bronchial mucociliary clearance is inhibited.
45
Therapeutic uses of muscarinic antagonists
1. GI actions:
- treat hyermotility and spasm associated with GI disease (IBS)
- Dicycloverine
2. Resp. actions:
- Treatment of COPD and acute asthma; as bronchodilator
- Ipratropium
3. Urinary tract:
- relieve muscle spasm accompanying infection
4. CVS actions:
- Treating bradycardia associated with MI
- Atropine
5. Overactive bladder:
- Reduce spontaneous myocyte activity
- decrease frequency and intensity of detrusor activity
- M3 receptor antagonists
- Adverse reaction - dry mouth, constipation, blurred vision, cardiac arrhythmia
46
Botulinum toxin..
- Botulinum toxin A (BTX-A) most potent and have a longer duration of action
- Administered and act in a site specific manner
47
Type of neuromuscular blocking drugs
1. Non depolarising: Block Ach receptors
| 2. Depolarising: Agonists at Ach receptors
48
Examples of competitive antagonists of Ach at mNicotinic receptor:
Tubocurarine analogues
1. Mivacurium
2. Atracurium
3. Vecuronium
4. Pancuronium
49
How depolarising agent act as neuromuscular blocking drugs?
- Sustained mNicotinic agonism at NMJ -> depolarisation block
50
Depolarising agent (suxamethonium) is contraindicated in..
1. Neuropathies
2. Myopathies (esp malignant hyperthermia)
3. Burns/severe trauma (hyperkalaemia -> risk of arrhythmia)
51
Example of AchE inhibitors (indirect cholinergic agonist)
1. Short-acting quaternary alcohols:
- e.g. edrophonium
- Bind to anionic site -> prevent Ach access
- Readily reversible -> brief action
- Used in diagnosis of myasthenia gravis
2. Medium acting Carbamyl esters
- e.g. neostigmine, physostigmine (longer acting)
- Carbamyl transfer to anionic site, then slow hydrolysis
- As reversal of NMJ block, myasthenia treatment
- Also Alzheimer's (doneprezil, tacrine)
3. Irreversible block
- e.g. echothiopate (eye drop for glaucoma), dyflos, melathion
- Phosphorylate ser203 at active site; stable bond so long lasting
- Reversible within first 1-2 hours using pralidoxome
52
Types of cholinesterase inhibitors
1. Carbamates (physostigmine, neostigmine)
| 2. Phosphates (isofluorophate)
53
Example of beta blockers
1. Atenolol
| 2. Propanolol
54
Example of direct acting adrenoreceptor agonists
1. dobutamine
2. epinephrine
3. phenylephrine
55
Example a & b blockers
Cervedilol
56
dobutamine
1. direct adrenoceptor agonist
2. Effects:
- Cardiac stimulation (B1)
- Vasodilation (B2)
3. clinical use:
- cardiogenic shock
- acute heart failure
- cardiac stimulation during heart surgery
4. side effect - arrhythmias
57
epinephrine
1. Effects:
- Vasoconstriction and increase BP (a1)
- Cardiac stimulation (B1)
- Bronchodilation (B2)
2. Side effects:
- Hypertension
- Vasoconstriction
- Arrhythmias
58
cocaine
1. Effects:
- Inhibition of norepinephrine reuptake
2. Side effects:
- hypertension
- cardiac damage
- necrosis of nasal mucosa (abuse)
59
Example of indirect acting adrenoreceptor agonists
1. amphetamine
2. cocaine
3. ephedrine
60
phenylephrine
1. Effects:
- Vasoconstriction, increase BP, mydriasis (a1)
2. Side effects:
- Bradycardia
- Hypertension
61
prazosin
1. MOA: competitive a1-blocker
2. Effects:
- vasodilation
- decrease vascular resistance and BP
- relax bladder neck and prostate
3. Clinical use: hypertension
4. Side effects:
- hypotension
- tachycardia
- nasal congestion
62
ephedrine
1. Effects:
- vasoconstriction (a1)
2. Clinical use - nasal decongestion
3. Side effects:
- hypertension
- tachycardia
- insomnia
63
amphetamine
1. Effects:
- increase norepinephrine release
2. Side effects:
- hypertension
- tachycardia
- dependence
64
atenolol
1. MOA: B1-blocker
2. Effects:
- decrease cardiac rate, output, AV node conduction & O2 demand
- decrease blood pressure
3. Clinical use: hypertension, angina, acute MI, arrhythmia
4. Side effects:
- Cardiac failure
- Bronchoconstriction
65
phentolamine
1. MOA: competitive a1 and a2 blocker
2. Effects:
- Vasodilation
- Decrease vascular resistance and BP
3. Side effects:
- Hypotension
- tachycardia
- nasal congestion
66
Examples of a-blockers
1. Prazosin
| 2. Phentolamine
67
carvedilol
1. MOA:
- B1 and B2 blocker
- a1 blocker
2. Effects:
- Vasodilation
- decrease heart rate and BP in patient with hypertension
- increase cardiac output in patient with heart failure
68
how to count BP?
cardiac output x total peripheral resistance
69
how to count cardiac output(CO)?
heart rate (HR) x stroke vol (SV)
70
define preload
the ability of the ventricles to stretch and fill with blood
71
define afterload
the ability of the ventricle to empty by pushing against systemic vascular resistance
72
parasympathetic effects on the heart
- input via vagus nerve causes decrease HR (dominates)
73
sympathetic effects on the heart
- input to SA node causes increase HR
| - increase heart contractility
74
propanolol
1. MOA: B1 and B2 blocker
2. Effects:
- decrease cardiac ratem otput, AV node conduction & O2 demand
- decrease blood pressure
3. Clinical use: hypertension, angina, arrhythmia, acute MI
4. Side effects:
- cardiac failure
- bronchoconstriction
75
function of renin
- secreted by the kidney to increase BP or blood volume
| - converts angiotensinogen -> angiotensin 1
76
function of angiotensin-converting enzyme (ACE)
converts angiotensin 1 -> angiotensin 2 in lung
77
actions of angiotensin 2
1. cause vasoconstriction = increase TPR
2. cause release of aldosterone -> promote Na & water reabsorption in kidney -> increased blood volume
3. negative feedback to release renin
4. stimulate thirst in hypothalamus
5. stimulate sympathetic outflow`
78
Principles of treatment of hypertension
1. Reduce left ventricular systolic performance
- negative inotropes (beta blockers)
- Calcium channel blockers (verapamil)
2. Reduce blood volume
- Diuretics (thiazide, loop diuretics & potassium sparing diuretic)
3. Reduce venous tone and thus venous return
- Central sympatholytics (clonidine) act to reduce synpathetic tone
4. Reduce arterial tone (resistance)
79
drugs to reduce arterial tone in hypertension eg: resistance
- ACE inhibitors
- angiotensin receptor blockers
- K+ channel openers
- NO donors
- A1- blockers
- mixed A and B blockers
80
treatment of cardiac failure
1. diuretics and nitrates (A-blocker) to reduce preload
2. digoxin to increase capacity of muscle contract
3. ACE inhibitors and A-blocker to reduce afterload
81
management of chronic heart failure
1. ACE inhibitors
2. diuretics and nitrates
3. B-blockers
4. ACE inhibitor and ARB
82
What are the adaptive response when in cardiac failure?
1. Cardiac dilatation
- CO increases as length of muscle fibre is increased
2. Sympathetic drive
- Increased preload, contractility, afterload
3. Renin angiotensin system
- Aldosterone causes sodium retention
- Angiotensin II causes peripheral vasoconstriction
(increase preload, contractility, afterload = increase O2 demand and eventual decompensation)
83
Principles of treatment of cardiac failure
1. Reduction of preload
- Diuretics (decrease blood volume)
- Nitrates
- a-blocker (venodilation)
2. Increased capacity of the myocardium to contract
- Digoxin
3. Reduction of afterload
- ACE inhibitors (vasodilation)
- a-blocker (vasodilation)
4. Counteract activation of sympathetic nervous system
- B-blocker
5. Counteract activation of RAAS
- ACE inhibitors
84
which type of adrenoreceptors (sympathetic nerves) dilate the arteries/veins?
B2 adrenoreceptors
85
what is variant angina?
vasospasm and temporary reduction of coronary blood flow
86
define stable angina
- chronic narrowing of coronary arteries due to inadequate blood flow
87
define unstable angina
- formation and dissolution blood clot (thrombosis) in coronary artery
- coronary blood flow reduced causing decreased O2 supply
- MI if clot completely occludes coronary arteries
88
Principles of treatment of angina
1. Dilation of arteries and veins
- Calcium channel blocker
- Nitrates
2. Reduction of heart rate and contractility
- Beta blocker
- Clacium channel blocker
3. Prevention of thrombus formation
- Anticoagulant
- Anti platelet drugs
89
Class 2: beta blockers are used to treat..
1. Arrhythmia caused by catecholamines
2. Arrhythmia originating from SA/AV nodes induced by stress
3. Effective for Sup. Ventricular and Ventricular arrhythmia
4. Contraindicated in asthma
5. Side effect: cardia depression and bradycardia
90
Principles of treatment myocardial infarction
1. Vasodilation
- Nitrates
- ACE inhibitors
- ARBs
2. Cardiac depression
- beta blockers
3. Antiarrhythmics
4. Thrombolysis (primary)
- Plasminogen activators
5. Analgesics
- morphine
6. Anti thrombotics (secondary)
- Anticoagulant
- Anti platelet drugs
91
phase 0 action potential (AP)
1. rapid depolarization
| 2. Na and Ca2 channels open
92
voltage for resting membrane
-70mV
93
phase 3 of AP
1. K+ channels open
| 2. Hyperpolarization
94
phase 1 and 2 action potential
1. Na and Ca2 channels close
2. K channels open
2. Repolarization
95
phase 4 of AP
1. K channels close
| 2. Recovery
96
How parasympathetic (vagal) nerve endings slows the heart rate?
Vagal nerve release Ach, acting on mAChr -> open K+ channels -> decrease slope of pacemaker potential -> decrease HR
(opposite effect of noradrenaline)
97
what phase of AP in RS ECG?
phase 1 and 2
98
what phase of AP in Q ECG?
phase 0 and 1
99
causes of arrhythmias
1. cardiac ischemic
2. excessive discharge or sensitivity to autonomic transmitters
3. exposure to toxic substances
100
what phase of AP in T ECG?
phase 3
101
types of vaughan williams classification
Class 1: Na channel blockers
Class 2: B-blockers
Class 3: K+ channel blockers
Class 4: Ca2 channel blockers
102
treatment of cardiac arrhytmias
use Vaughan Williams Classification
103
Class 1A:
- cause moderate phase 0 depression
- prolong repolarization
- increase duration of AP (slowing conduction)
- decrease HR
- use only for ventricular arrhythmias
- drugs: disopyramide
104
non-vaughan williams classification drugs
1. adenosine
| 2. digoxin
105
Class 1C
- strong phase 0 depression
- no effect on depolarization and duration of AP
- inhibit abnormal automaticity
- drugs: flecainide (slow conductions in all part of heart)
106
Class 1B
- weak phase 0 depression
- shorten depolarization and repolarization
- decrease duration of AP
- drugs: lidocaine (in ventricular cell, and digitalis associated arrhythmia)
107
Class 3
- delay repolarization
- prolong refractory period and AP
- use in SVT and VT
- drugs: amiodarone (could cause Na channel blockade), bretylium, sotalol
- All 3 agents - torsades de pointes
108
Class 2
- Block sympathetic stimulation of heart
- increase K+ conductance (slow HR)
- increase refractory period and prolong AP
- e.g. propanolol, atenolol, sotalol
109
Drugs used in heart failure
1. Diuretics
2. Nitrates
3. ACE inhibitor and ARBs
4. B-adrenoreceptor blocker
5. Digoxin
110
Drugs used in hypertension and angina
1. ACE inhibitor and ARBs (v TPR = vasodilation)(^ Blood Vol.)
2. Calcium channels blockers (v contractility, TPR, HR)
3. Diuretics (v blood vol.)
4. Adrenoreceptor acting drugs
5. Vasodilator (GTN)
111
Class 4
- slow stimulus conduction through the AV node
- strongly affect conduction from atria to ventricles
- Very useful for supraventricular arrhythmia (not ventricular)
112
Drugs used in MI
1. Analgesia
| 2. Thrombolysis & other antiplatelet therapies
113
digoxin (cardiac glycoside)
1. increase vagal tone
2. decrease HR in atrial fib
3. prolongs the effective refractory period
4. positive inotropic effect in heart failure
5. May induce cardiac arrhythmias:
- block AV conduction
- increase ectopic pacemaker activity
114
adenosine
1. depresses Ca current influx
2. increase K+ conductance
3. slows AV node conduction
4. termination of SVT
5. replaced verapamil for SVT
6. given IV only
115
Example of ACE inhibitors
Captopril
116
MOA of ACE inhibitors
1. Vasodilation: reduce vascular tone
| 2. Reduction in aldosterone secretion: decrease blood vol.
117
Therapeutic use of ACE inhibitor in hypertension
1. in diabetes mellitus with hypertension
2. most effective in high renin hypertension
3. more effective in white vs black patients
4. excellent for patient with concomitant congestive heart failure
5. considered in asthma instead of beta blocker
118
drugs for hypertension for <55 years patients
ARB
119
Example of ARBs or AT1 receptor antagonists
losartan
120
drugs for hypertension for >55 years patients
- Ca channel blocker or
| - diuretics
121
Two groups of Calcium channel blockers
1. Non dihydropyridines (verapamil)
| 2. Dihydropyridines (nifedapine): primary action on arterioles
122
Effects of nifedapine.
1. Dilation of arteries and arterioles
2. Fall in BP (decreased TPR)
3. Reflex tachycardia
123
Which drug is the best in low renin hypertension (black and elderly patient) ?
Nifedapine
124
the use of non selective alpha blocker (phentolamine)
1. Postural hypotension > induce tachycardia
| 2. pheochromacytoma
125
clonidine MOA in treating hypertension
1. Central action:
- reduce sympathetic tone -> vasodilation & reduced HR
2. Prejunctional action:
- Reduces noradrenaline release
3. Vascular smooth muscle:
- Open Ca2+ channels and cause vasoconstriction
126
losartan (ARB)
1. block angiotensin 2 from stimulate pressor effect at AT1 recep.
2. antihypertensive effects
3. lack of bradykinin effects
4. promote renal excretion of Na and water
127
effects of ACE inhibitors eg: captopril
1. hypotension
2. reduced glomerular filling pressure
3. accumulation of bradykinin cause cough
4. hyperkalemia
5. hyponatraemia
128
loop diuretics
- act in loop of Henle
- most effective and commonly used
- 25% Na retention
- cause hypokalemia
129
major categories of diuretics
1. loop diuretics (furosemide & bumetanide)
2. thiazides (hydrochlorothiazide)
3. potassium-sparing
- aldosterone antagonist (spironolactane)
- non aldosterone antagonist (amiloride)
4. osmotic (mannitol)
130
potassium-sparing
- helps reducing the hypokalemia due to loop diuretic & thiazide.
- drugs: spironoloctoone
131
thiazides
- act in DCT
- effective in mild cases only
- 5% Na retention
- cause hypokalemia
- drugs: hydrochlorothiazide
132
nitrates (GTN)
- vasodilator
- release NO that relaxes vascular SM
- Antianginal actions:
- reduce cardiac O2 consumption
- reduce preload and afterload
- redistribution of blood flow towards ischaemic area
- relief of coronary spasm
133
side effects of B-blocker
- bradycardia
- heart failure
- bronchospasm
- coldness of extremities
- hypoglycaemia
134
amrinone
- PDE inhibitors
- increase cAMP
- cAMP phosphprylate Ca channels -> increase Ca entry into the cell
- increase cardiac muscle contract
- vasodilating effect
135
inotropes
- increase force of contraction of heart
- increase intracellular cardiac [ca2+]
- drugs: digitalis (digoxin), dobutamine, amrinone (PDE inhibitor),
noradrenaline
136
levosimendan
- calcium sensitizer
| - increase contraction at normal Ca levels
137
Example of thrombolytic therapy
1. Streptokinase
| 2. Recombinant tissue plasminogen activator
138
recombinant tissue plasminogen activators
- directly activates plasminogen
- not antigenic
- initiate conversion plasminogen to plasmin to induce fibrin degradation
139
streptokinase
- protein extracted from streptococci
- activates plasminogen
- initiate conversion plasminogen to plasmin to induce fibrin degradation
