L1 Cardio/vascu (fadil)

Question 1

The general scheme of the Adrenergic or Flight/Fight system
(idk y I made this)

Answer 1

• Activating factors which work on the HPA
• Then activate adrenergic system
• Followed by release of NE or EPI to act on receptors to illicit a response/function

Question 2

Describe the receptor actions for:
1) A1 in smooth muscle
2) A2 in smooth muscle
3) A2 Centrally/CNS (when does this occur)

*What is the difference between A1 and A2 GPCR

Answer 2

1) A1 Smooth : NE/EPI stim GQ -> GQ stimulates PLC-> IP3 increases =
Ca+ increase and more contraction

2) A2 Smooth: GI stim -> cAMP decrease -> MLC activated -> Contraction

3) A2 CNS: GI -> cAMP decrease -> NE release inhibited

-A1 uses the GQ coupled G protein while A2 uses GI or G inhibitor protein
-A2 in the CNS (pathway #3) works as a counter regulatory negative inhibition pathway to decrease vascular tone and blood pressure. This is when “you have gotten away from the lion” as in you don’t need an increase in bp or vascular tone so you are inhibiting sympathetic pathway.

Question 3

PrazOSIN and TerazOSIN
1) what type of blocker/inhib (receptor) / Selective or non
2) type of inhibition/ Indication of use

Answer 3

*“OSIN” so immediately think A1 blocker

1) selective A1 blockers
2) primarily used in hypertension management (COMPETITIVE)

How? —> by inhibiting A1 we stop Ca+ release so no contraction of VSM

Question 4

Phenoxybenzamine and Phentolamine

1) type of blocker (receptor/selective or non)
2) MOA (both same)
3) Net outcome
4) Adverse effects and compared to Prazosin and Terazosin
(Hint B1 receptor)

Answer 4

1) both are non selective A1 A2 blockers but have 2 diff mech and act on 2 diff tissue

2) MOA - drugs nonselectively block A1 and A2 in peripheral smooth muscle and cause relaxation

3) Net outcome = reduced vascular pressure and controller hypertension via blocking A1 A2

4) *** Phenoxy and Phento cause blocking of A2 in sympathetic terminal which disrupts negative feed back for NE release. So even though you have a reduction in hypertension/ afterload Heart Rate will increase because NE works on B1 receptors and the drug has no involvement in blocking Beta receptors. Compared to Prazosin and terazosin although they do not have as great of an effect on reducing peripheral muscle constriction they won’t have this adverse effect of disrupting NE regulation.

Question 5

Clonidine, Guanfacine, Methyldopa
1) what kind of drug and which receptor
2) clinical indication

Answer 5

1) these are Alpha-2. Adrenergic Agonist
- remember these will activate the NE negative feedback loop so less or more regulated NE will be released
- Compared to Phentolamine (Alpha blockers/ “antagonist”) which block A2 receptors disrupting the NE feedback loop

2) severe vasoconstriction and hypertensive crisis because we activating negative feed back loop enhancing suppression of NE

Question 6

Give a general scheme for Beta Receptors and the Heart (cardio pharm)
3 steps

Answer 6

1) B1 stimulated by a ligand (NE)
2) Gs protein stimulates release of Ca+ from Sr
3) more contraction via ventricular mycoytes

Question 7

Beta receptors and Kidneys

Answer 7

1) B1 stimulated
2) Gs stimulated -> Ca+ release -> Renin release
3) RAAS and hypertension

Question 8

B2 receptors gen scheme

Answer 8

1) B2 stim
2) Gs-> cAMP increase
3) MLC Kinase inhibited = relaxation

Question 9

Propranolol
1) kind of drug
2) Random question he gave:
Why should you not give Propranolol to an asthmatic patient

Answer 9

1) non selective Beta blocker
2) You wouldnt give an asthmatic patient a non specific Beta blocker because they can cause bronchial spasm (example he gave was propranolol)

Question 10

When to use Beta blockers

Answer 10

Heart failure
Hypertension
Arrhythmia
Ischemia
etc…

Question 11

The major channels targeted in cardiovascular pharmacology and cardio diseases are:
(2 but 1 is most important)

Answer 11

** L type Ca+ channels are the most important target for drugs
T type is the other ca channel

Question 12

1) A patient has either of the following issues:
Coronary Artery disease
Angina
Cardiac Arrhythmia
Blood Vessel Complications

• Which drugs can you administer, what type of drugs are they and what are they inhibiting

Answer 12

1) drugs to be administered are calcium channel blockers:
Verapamil, Diltiazem, Amlodopine
and they inhibit L type Ca+ channels in vascular system and heart leading to a decrease in heart rate and hypertension

Question 13

Name the 2 B1 selective drugs

Answer 13

** This all he wanted us to know, he didn’t expand on these**
Atenolol and Metoprolol

Question 14

Name the 2 Non-Selective Alpha and Beta drugs

Answer 14

** This all he wanted us to know, he didn’t expand on these**
Carvedilol and Labetalol