Lecture - Pharmacology (Adrenergic Modulators) Flashcards
Factors controlling BP:
- What three things is cardiac output controlled by and what oragns/system controls those three?
- What is peripheral resistance controlled by? (3) And is each rapid or slow?
- So the ANS innervates the heart - what part of that speeds up the heart, what slows it down? What nerves are the parasym/symp and where do they terminate?
- How does the brain know whether to speed up or slow down the heart?
- Does the symp or parasym lead to renin release?
- Have a careful look at diagram - the cardiac accelerator nerve is the sym and the vagus is the parasym
- It receives sensory information from baroreceptors
- Symp
Control of cardiac output and vascular tone:
- Sympathetic innervation of heart: what neurotransmitter at end and on what receptor (primarily what type?)
- Sympathetic innervation of the BV: what neurotransmitter at end and acts on what receptor?
- Parasympathetic innervation of heart: what neurotransmitter at end and at what receptor? Where are these receptors?
- Endocrine - what does circulating a_____ affect? At high concentrations, it also affects what? What organ releases this neurotransmitter?
ANS in control:
- So what do the alpha adrenoreceptors do (adrenergic receptors) when (I think) the NE (noradrenalin/norepinephrine) lands on them?
- What two things are mediated by the beta-1 adrenoreceptors (Sym)? What nerve releases what neurotransmitter on these receptors? Where will you find these receptors?
- What’s mediated by the M2 receptor (parasym)? What nerve releases what neurotransmitter on these receptors? Where will you find these receptors?
NeuroEndocrine system:
- Sym or Parasym to act on kidney to release renin?
- Increased renin in kidney is mediated by what receptors?
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Age and your BP:
- Incidence of _______ (______ BP) increases progressively with age
- What is the pattern of systolic blood pressure in terms of increasing/decresing throughout life?
- What about diastolic blood pressure?
- Until the age of 50, which of the SBP or DBP is a more potent risk factor for coronary heart disease? When after 50, which one is more important?
- Increased arterial stiffness is the vascular phenotye of _____ _______ especially of the ______ _______
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- Why should we treat hypertension (HTN)?
- What’s the goal of therapy?
- Bc it damages organs (kidneys, heart, eyes, brain etc) and carries a risk fo CV disease eg MI
- Goal of therapy = maintain BP at near normal limits with minimal ADRs so like use drugs appropriately, dont ovredose and if you use more than one drug - make sure no adverse interactions
HTN treatment:
- What first thing do you do for treating HTN? What if they don’t work?
- What is now the first line of drug to use supported by BPAC? This is particularly in the presence of what?
- If you can’t tolerate ACE inhibitors, then what do you use? What are they preferred in the absense of?
- What are compelling indications - give some examples too
If there are no contraindications, current hypertension guidelines recommend to start the treatment with what?
- What is not suitable for ISH control (predominantly in elderly)? Why elderly?
- A single agent will control BP in how many patients?
- If a single agent doesn’t control BP, then what to do?
-Elderly: using drug to impact heart but actual problem is in arteries stiffening
Beta-adrenergic receptor antagonists (B-blockers)
- Thinking back - what does adrenalin bind to?
- What does the sympathetic nervous system release its NE/NA on?
- So, what do B-blockers inhibit the binding of to B-receptors? They’re a large family of drugs with varying properties
- Degree of response is proportional to the level of what? (eg during….)
- Main therapeutic use on CVS is through inhibition of what kind of B receptors?
- B2 receptors are found where? What does this mean for B-blockers and asthma?
- What is the 1st generation and 2nd generation B-blocker and what receptors do they work on? So which one given to the asthmatic patient? …….buuuuut?
- NA/NE on the B2 receptors in the resp airways leads to relaxation so open them up. With these drugs, they won’t let that happen and in asthma, small airways already so bad combination.
- Still, metoprolol can still somehow get higher dose and yeah
Pharmacological actions of B-blockers
- Primary antagonise what?
- Decrease CO and BP by 2 negative actions; what are they and what do they decrease (rate/force of contraction)?
- They also decrease what output in the kidney’s juxtaglomerular cells?
- Their anti-hypertensive effect is mainly due to adrenergic block - by what 3 things happen? (last one is to do with chronic use)
- Although primary action is on cardiac output, what does long term treatment with B-blockers ulimately decrease?
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Pharmacological value of B-blockers
- So they have rate control - what is this effect called (negative c_____). What do they inhibit that leads to this decreased rate of contraction? Why is this important in arrythmia?
- They also decrease wrok of heart - what two actions are these (negative _____ and _____). This will consequently reduce what? Why is this important in angina?
Prinicpal therapeutic uses of B-blockers:
What is carvedidol? What receptors does it work on? (slide 28)
What 4 main things are b-blockers used for and why? What last two things is it used for?
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What are adverse effects of B-blockers:
- What 6 things do they provoke? Know these
Lol they’re used for heart failure but can also provoke it……
What are other adverse effects of B-blockers? (2)
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Why are B-blockers not considered for first line HTN treatment?
What can you say about newer 3rd generation B-blockers like carvediol and nebivolol?
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Pharmacokinetics:
- What does hydrophilicity generally tend to confer in terms of metabolism, half life and CNS?
- What does lipophilicity tend to confer in terms of oral, metabolism, first pass effect, half life, volume of dist, CNS?
- Metaprolol/propranolol - are they lipophilic or hydrophilic? So what can you say about BBB, oral and bioavailability for them?
- Atenolol - is it higher or lower lipid solubility? So what can you say about BBB, renal and half life?
- Betablocker plasma concentrations can aslo vary as a consequence of varying what?
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Centrally acting alpha2 antagonists - mainly presynaptic actions:
This just means they act in CNS
- What are the 2 drugs used?
- What will these a2 agonists produce?
- They’ll produce initial hypersensitive response due to vascular effects
Central action of clonidine:
- What type of alpha-2 receptor is this an agonist for?
- How does it work?
- Can initial or higher doses affect vasculature? WHat receptor do they affect?
Clonidine is a a2 agonist. It gets into synaptic cleft centrally and impacts on a2 receptors (not a1) - predominantly found presynaptically
NE is stored in vesicles - released in response to depolarisation and across synaptic cleft and acts on the post-synaptic cleft’s beta or alpha receptors etc. There is a feedback pathway: when sufficient stimulation, NE stimulates the pre-synaptic alpha receptors and tells system to sto realeasing NE (negative feedback) so sufficient NE stops excessive NE output.
Clonidine gets into synaptic cleft - binds onto alpha-2 receptors and does the same thing. It tells the pre-synaptic terminal to stop releasing NE.
Now you’ve stopped all downstream affects of the sympathethic nervous system - no more (nor?)adrenalinin output onto the vasculature or heart or any other significant organs
A2 receptors also in vasuclarture so if you give this drug for the first time, you can impact this and cause vasocontriciton - BP can increase very quickly with acute doses of clonidine so need to start off small (build up slowly) doses (so it gets into brain without heaps of effects on vasculature) and then build up so you get the effect in brain more than vasculature
