Pharmacology Flashcards
Give 2 ways you can regulate HR/decrease SAN frequency
e.g. to treat angina, HF, arrythmias
- VGCa2+C blockers aka CCB to slow the phase 0 upstroke
- Block the If channels to increase phase 4 reducing myocardial O2 demand
Dihydropyridines are an example of which type of Calcium Channel Blocker?
Vascular Selective
e.g. Amlodipine
Diphenylalkamines are an example of which type of Calcium Channel Blocker?
Cardiac Selective
e.g. Verapamil
Benzothiazepines are an example of which type of Calcium Channel Blocker?
Vascular AND Cardiac selective
e.g. Diltazem
How can CCBs worsen HF and cause heart block?
- They can block cardiac myocyte action impairing contraction
- they can block conduction at the AV node
Ivabradine is an example of what type of drug?
If Channel Blocker
What action does Ach have on the autonomic control of SAN?
- Acts at M2 recptors via Gai
- decreased PKA, decreases If activiity
- reduced HR (parasympathetic)
What effect B-blockers have?
e.g Atenolol
Reduce sympathetic effect on SAN so HR slows reducing work and o2 demands on heart
When should you not use B-blockers?
Asthmatics With CCBs (both may lead to bradycardia)
How do Muscarinic Receptor Blockers stabilise CO?
e.g. Atropine
reduce vagal parasympathetic action on SAN so remove inhibitory vagal tone on HR, (HR increases)
Name 3 categories of ionotropic of agents and an example of each.
GaS Agonists e.g. Adrenaline. Dobutamine
PDE Inhibitors e.g. Amirone PDE 3i (heart specific)
Cardiac Glycosides e.g. Digoxin
Calcium Sensitisers e.g. Levosimedan, Omecamtiv
Why might a HF patient be given a GaS agonist such as glucagon in stead of Adrenaline/doputamine?
If the patient is taking B-blocker medication they will be given glucagon as the others will be innefective
How does the ionotropic agent, PDE3 inhibitor Amirone work?
causes c.AMP to build up, activates PKA
so more VGCaC and Ca influx
More CICR, TnC and contraction
How does digoxin increase contractility?
effect on HR?….
Inhibits the Na/K ATPase so Na+ builds up in the cell and there is less of a gradient for Ca2+ extrusion via the Na/Ca exchanger.
More Ca uptake into stores leading to more CICR
…it increases vagus activity so decreases HR
What is the advantage of calcium sensitisers over GaS agonist in increasing ionotropy?
GaS agonists are proarrythmyogenic as they increase HR. Also the Ca2+ rise they induce requires more Ca2+ ATPase activity/more 02 consumption
vs
Calcium sensitisers only increases the sensitivity of the contractile apparatus (not pro-arrythmyogenic)
How does the calcium sensitiser Levosimedan act?
Binds to TnC and increases binding of calcium to TnC
How does the calcium sensitiser Omecamtiv act?
Increases actin-myosin interactions in absence of Ca2+ rise
Give 2 reasons of giving a B-blocker in chronic HF.
- prevent overworking by slowing HR and increasing coronary perfusion
- reduce contractility so decrease 02 demand for more efficient functioning
Decreasing BP can increases SV/CO.
Give 2 examples of drug types that do this?
Diuretics-via decrease blood vol, and CVP
AngRB-via blocking v.constriction so v.dilation results hence reduced TPR. Also less aldosterone so less water reabsorption, lower blood vol
ACEi
L-Arginine with endothelium NO Synthase —> NO
NO causes vasodilation.
Give and example of a drug that mimics this process and what is it used for.
The nitrate donor GTN
Used to dilate coronary arteries during cardiac pain
How does Sildenafil act?
- it inhibits phosphodiesterase 5 which means less c.GMP is degraded
- hence more NO release and vasodilation to maintain blood flow
Name 2 pharmacological vasoconstrictor agents and their mechanism of action.
Norad - acts on a1 VSMC to increase TPR and BP and is cardiac protective
Adrenaline - in high conc is given to act at a1 VSMC as well as B1 receptors on heart to increase BP and HR
Pharmacological vasodilator agents block/inhibit -ARB -ACE -a1 -ETA give an example of each
- ARB - Losartan
- ACEi - Enalapril
- a1-antagonist - Prazposin
- ETA antagonist - Bosentan
Where does the pharmacological vasodlilator agent, ‘Nicrorandil’ act?
- at K+ channels opening them
- hyperpolarisation
From what level is the sympathetic outflow?
NT used?
T1-L2 Thoracolumbar
Ach on Nic at pre. NA on a/B at post.
From where is the parasympathetic outflow?
NT used?
CNIII, VII, IX, X and S2, S3, S4 - craniosacral
Ach on Nic at pre and at post-ganglionic fibres
From what amino acid does DA, NA and A originate?
Tyrosine
Dopamine is converted into NA by dopamine hyroxylase. What happens to the NA?
It is released from the nerve
In the adrenal medulla, PNMT can convert it to Adrenaline
What effect does reserpine have on Adrenergic transmission?
- prevents NA storage in vesicles
- NA is broken down by MAO in cytoplasm
- less NA released/decreased symp. activity
What effect does tyramine have on Adrenergic transmission?
- facilitates release by displacing NA from vesicles into cleft
- increased symp. activity
What causes the fusion of Ach vesicles with the pre-membrane?
Ca2+ entering the bouton
Where is Ach broken down and by what?
In the synaptic cleft
By acetylcholinesterase
How does botulism toxin affect cholinergic transmission?
- degrades Ach vesicles so inhibits cholinergic motor activity
- > dry mouth, blurred, muscle paralysis
How does the Nic. Agonist, ‘Suxamethonium’ cause muscle relaxation?
- stays at Nic receptor due to poor dissociation
- sustained EJP leads to Na+ channels inactivating
- prevents APs. This is ‘depolarising block’
How is bradycardia brought about via parasympathetic system?
- Vagus releases Ach, this acts at M2 receptors on SAN
- decreased frequency of pacemaker potentials
How does stimulation of the pre-synaptic a2 receptor by excess NT (e.g. NA) cause decrease NT release?
Gai - PKA decreases, less Ca2+ activity as less channels phosphorylated
So less vesicles fuse
Where does NA preferentially act?
alpha receptors (coronary/skeletal muscle = v.rich in B receptors so get vasodilation here instead)
