PHARM - Introduction to Cardiovascular Pharmacology - Week 4 Flashcards
What forms the high and low pressure components of the cardiovascular system? What percentage volume of blood can be found in each?
High pressure - arteries/arterioles, has ~17% of blood
Low pressure - veins/venules, has ~70% of blood
Do capillaries have smooth muscle?
No
What is the formula for blood pressure?
BP = cardiac output x total peripheral resistance
What is the formula for cardiac output?
CO = heart rate x stroke volume
What three components control total peripheral resistance?
Humoral control
Sympathetic control
Local control
Define preload.
Filling pressure of the right atrium/ventricle
What is defined as the resistance to outflow from the left ventricle?
Afterload - total peripheral resistance
Do the sympathetic and parasympathetic systems control both heart rate and contractility?
Sympathetic - controls heart rate and contractility
Parasympathetic - controls heart rate only
Define total peripheral resistance.
It is the sum of all vascular resistances in the systemic circulation
In what manner do arteries supply tissue/organs?
Parallel circuits
Describe Poiseuille’s Law, the equation, and what it means.
TPR ∝ 1 / ri^4
TPR = total peripheral resistance
ri = vessel radius
Arteriolar diameter determines resistance to local blood flow in a particular vascular bed
Are arteriolar walls thicker in relation to lumen diameter? How does this affect the effect of contraction on resistance?
Arteriolar walls are thicker than lumen diameter, and so changing contraction affects resistance significantly.
Name an example of a sympathetic factor that controls arteriolar diameter.
Noradrenaline
Name two passive factors that control arteriolar diameter.
Pressure
Architecture
Consider elevated blood pressure. What 2 structural changes happen to blood vessels.
Why do these changes occur?
Hypertrophy of smooth muscle
Decreased vessel lumen
This decreases wall stress with increasing pressure
Keeping Poiseuille’s Law in mind, describe the impact on blood pressure a constrictor stimulus will have on blood pressure.
If TPR ∝ 1 / ri^4, and BP = CO x TPR, then as ri increases, BP will increase more for hypertensive patients for any given constrictor stimulus.
Describe the optimal, normal, and normal high values for blood pressure (systolic and diastolic).
Optimal
Systolic - <120
Diastolic - <80
Normal
Systolic - 120 - 129
Diastolic - 80 - 84
Normal High
Systolic - 130 - 139
Diastolic - 85 - 89
Describe the grade 1, 2, and 3 values for hypertension (systolic and diastolic).
Grade 1
Systolic - 140 - 159
Diastolic - 90 - 99
Grade 2
Systolic - 160 - 179
Diastolic - 100 - 109
Grade 3
Systolic - ≥180
Diastolic - ≥110
Describe the value for isolated systolic hypertension (systolic and diastolic).
Systolic - ≥140
Diastolic - <90
Describe primary/essential hypertension, the percentage of patients that fall under this category, and the cause (7). What age group typically falls under this category?
Primary/essential hypertension has no apparent cause. 90-95% fall under this category.
Typically occurs in patients >40 years
Possible causes are:
-genetic predisposition
-diet (high Na+)
-Obesity
-EtOH
-physical inactivity
-psychological factors
Describe secondary hypertension, the percentage of patients that fall under this category, and 3 possible causes.
Secondary hypertension has an identifiable cause. 5-10% fall under this category.
Possible causes are:
-renal disease
-endocrine disorders
-pre-eclampsia in pregnancy
What is the first choice therapy for hypertension treatment, what mmHg goal, and 5 factors that can lower pressure?
Lifestyle modifications, with a goal of diastolic blood pressure ≤80mmHg
Choices include weight loss, healthy diet, exercise, no smoking, and no coffee.
Do all antihypertensives have adverse effects?
Yes
Keeping in mind the formula for blood pressure, how can it be lowered (4)?
BP = CO x TPR
Reducing CO involves:
-decreasing sympathetic effects on the heart
Reducing TPR involves:
-decreasing plasma volume
-decreasing sympathetic effects on arteries
-deother mechanisms
Do a1 adrenoceptors increase or decrease TPR?
Increase
Do catecholamines increase or decrease TPR?
Increase
Does angiotensin II increase or decrease TPR?
Increase
Does NO increase or decrease TPR?
Decrease
What does angiotensin II act as an antagonist to?
B1 adrenoceptors
Name the three things that control heart rate, their effector molecule, the receptor it acts on, and where in the heart. Note the effect on heart rate.
Sympathetic system - using noradrenaline, acting on B1 receptors, increasing heart rate.
Adrenal gland - releases circulating adrenaline, acting on B1 receptors, increasing heart rate.
Parasympathetic system - using acetylcholine, acting on M2 recetors, decreasing heart rate.
They affect the SA node of the heart.
What two thing control stroke volume, their effector molecule, the receptor, the effect on stroke volume, and where in the heart.
Why is stroke volume affected?
Sympathetic system - using noradrenaline, acting on B1 receptors, increasing stroke volume.
Adrenal gland - releases circulating adrenaline, acting on B1 receptors, increasing stroke volume.
The receptors are on cardiac muscles.
These two systems increase force and contractility, thus increasing stroke volume.
Describe inotropic effect.
A change in the force of contraction.
Describe chronotropic effect.
A change in the rate of contraction.
Keeping in mind the formula for BP, describe the mechanisms of B1 antagonism.
BP = CO x TPR and CO = HR x SV
Antagonising B1 will decrease HR at the SA node, and decrease SV at cardiac muscles, decreasing cardiac output, and thus BP.
Describe the effects of B1 inhibition at the kidney, and the effect on blood volume, and thus BP.
Decreases renin secretion, decreasing volume, and therefore BP.
Give two examples of non selective B antagonists.
Propranolol
Oxprenolol
Give two examples of B1 selective antagonists.
Atenolol
Metoprolol
Are B antagonists typically lipid soluble?
Yes
Name 6 common adverse effects of B antagonists, and the mechanism if possible.
Cold extremities - peripheral vasoconstriction/loss of B mediated dilation
Fatigue - decreased cardiac output
Dreams and insomnia - CNS effects due to lipid solubility
Cardiac depression - elderly
Bradychardia
Bronchoconstriction - B2 inhibiton
Why are B antagonists contraindicated for patients with bronchoconstriction?
Its life threatening to them
What molecule is released in response to adrenaline, and how does this relate to the use of B blockers in diabetics? What does it increase the likelihood of, and why?
Glucose is released.
In diabetics, the use of B blockers increases the likelihood of hypoglycaemia as adrenaline-induced release of glucose from the liver is diminished.
Is diabetes a contraindication for B blockers?
Only poorly controlled diabetus.
Name 5 contraindications for B antagonists.
Athsma
Sinoatrial or atrioventricular dysfunction
Hypertensives with heart failure
Peripheral vascular disease
Patients with poorly controlled diabetus
Describe B antagonist drug withdrawal syndrome, and what can happen as a result. What is done to avoid this?
An upregulation of B receptors occurs during the blockade, resulting in increased sensitivity to endogenous catecholamines.
It can result in a rebound hypertension to higher levels.
Dosage must be tapered over eeks to months.
What is the drug of choice for B antagonism (which receptor, not drug name), hydrophilic or lipophilic, and why.
B1 is preferred, and hydrophilic.
This limits side effects.
