PVD Flashcards
Describe the role of alpha and beta receptors in the CVS system
Alpha receptors:
1- expressed in blood vessels, gut and skin, improves perfusion
2- a dilator, expressed in pre-synaptic terminals of the CNS, mediating NA release in order to ‘prevent an over-reaction’
Beta receptors:
1- expressed in heart, positive chronotropic and inotropic effects, ensures good perfusion
2- a relaxant, dilator, similar effects to alpha2. Located in lungs
Explain the effects of alpha and beta agonists and antagonists on CVS, and the indications for treatment
alpha 1:
- Agonists indicated Hypotension, Nasal congestion (phenylephrine and pseudoephedrine, acting locally), Glaucoma - Agonists mimic the SNS response - (Agonists: Noradrenaline, Oxymetazoline, Phenylephrine, Pseudoephedrine; - Antagonists: Prazosin, Tamsulosin, Phenoxybenzamine, Phentolamine) - Antagonists e.g. prazosin indicated in BPH and HTN
alpha 2:
- In ICU setting: Hypertension, Analgesia, sedation, agitation and others - (Agonists: Clonidine, Dexmedetomidine, Brimonidine aka the "idines") - No clinically relevant antagonists - Note: agonists are not really used clinically - Note 2: glaucoma and eyedrops
beta 1:
- (Agonists: Dobutamine, Adrenaline; Antagonists: Metoprolol, Atenolol)
- Agonists are fairly selective
- Note: dosage of adrenaline is inversely realted to selectivity
- Antagonists are cardioselective, and include metoprolol and atenolol, indicated for heart failure, tachyarrhythmias and hypertension ^[can use for HF when stable]
beta 2:
- (Agonists: Salbutamol (inhaled, Terbutaline)
- Agonists result in bronchoconstriction
- Non-selective antagonists, and vary in their selcectivity e.g. propranolol used in hypertension, tacharrhythmias, and migraines
- Care must be taken in prescribing if patient has asthma and COPD to prevent bronchospasm
Which sympathomimetic agents lead to bronchoconstriction?
- None-selective – some non-selective antagonists (β1 and βs) e.g., propranolol
- Indications: Hypertension, tachyarrhythmias, migraine
Describe the problem associated with sympathomimetic agents
Notwithstanding the advances in the science underpinning our understandings of adrenoreceptors, clinical pharmacology still largely concentrates on α-, and β-receptor agonists/antagonists:
- Still largely a descriptive pharmacology due to unavailability of specific agonists and/or antagonists in clinical practice.
- For clinical use, many different compounds (agonists/antagonists) commercially available, all with slightly different pharmacological profiles and kinetics.
- Lots of cross-over and dose-dependent actions.
Briefly descripe the use of sympathomimetics, vasopressors and inotropes in clinical practice
- Agents used in critical illness (predominantly).
- Using receptor activity and selectivity in clinical practice.
- Note that there is no perfect receptor selectivity so may have mixed results.
- Most are given by infusion due to a short half-life: therefore must be administered by continuous perfusion
Note also: vasopressors are not the same as inotropes
List the classes of medications associated with changes in peripheral vascular resistance
Pharmacologically Important Circulating Vasoconstrictors
Available as pharmacological agents:
- Noradrenaline (norepinephrine)
- Vasopressin
- Adrenaline (epinephrine)
- Dopamine
Available as pharmacological targets:
- Angiotensin II
- Calcium
Pharmacological Targets for Blood Pressure Control
- ACEI (Angiotensin Converting Enzyme Inhibitors)
- Angiotensin II
- Sympathomimetic Agents
- Diuretics, involved in managing tubular sodium/chloride reabsorption
- Aldosterone Antagonists
- Vasopressin: acts on kidneys and blood vessels
Note: location of action of kidney is related to its potency. Furosemides which target loop of Henle are more efficient in reabsorbing salts compared to thiazides
Describe the use of noradrenaline and adrenaline
Noradrenaline
- Mechanism of Action: Naturally occurring chemical that stimulates sympathetic system receptors (alpha).
- Note: cannot be administered peripherally, otherwise constriction of peripheral vessels and death of tissue
- Effect: Vasoconstriction, no effect on heart rate or force of contraction (has very little activity on beta receptors).
- Indications: Used to increase blood pressure.
- Administration: Only to be administered by infusion (i.e., not for bolus dosing) via a CVC.
Adrenaline
- Mechanism of Action: Naturally occurring chemical that stimulates sympathetic receptors (receptor activation is dose dependent).
- Effect:
- Low doses: Increased heart rate (chronotropy) and force (inotropy) via beta receptors.
- Higher doses: Vasoconstriction and has ‘less cardiac actions’ via alpha receptors.
- Indications: Can be given as a bolus dose or infusion (bolus for cardiac arrest and intramuscular for anaphylaxis).
Describe the use of dobutamine
- Mechanism of Action: Activates beta 1 receptors, which increase the force of contraction of the heart, but also peripherally vasodilates (drops BP).
- Effect: Inotropic agent (increases force of contraction), used in heart failure to improve cardiac output.
- Administration: Not for bolus injection, but can be administered continuously; can be used for acute heart failure or palliative management of chronic heart failure, low cardiac output states.
Describe some vasoactive drug classes and provide examples
- Calcium Channel Blockers: Amlodipine, Nifedipine
- Potassium Channel Blockers: Hydralazine (direct-acting), Minoxidil (refractory hypertension, debatable clinical use)
- α1 Antagonist: Prazosin
- Endothelin Antagonist (Pulmonary): Bosentan
- ACEI (Angiotensin Converting Enzyme Inhibitors): Captopril, Ramipril – first line drugs
- ARB (Angiotensin II Receptor Blockers): Irbesartan, Valsartan
- Nitrodilators (Venous): Glyceryl Trinitrate, reducing preload and oxygen requirements
Describe the medications that would be prescribed to 78-year-old patient with decompensated CCF (low ejection fraction)
- Adrenoreceptor to target
- agonists use in acute settings, helps heart contract better- Clinical effects: Reduced heart rate, improved cardiac contractility, and decreased peripheral vascular resistance.
- Chronic medications: Likely on diuretics, ACEI or ARB, possibly beta-blockers.
- Note: if acutely unwell, withhold the ACE and stick with BB
- Influence on acute treatment: Consider interactions with beta-blockers if they were already on chronic treatment.
Describe the medications that would be used to treat a young patient with septic shock
- Adrenoreceptor to target: Agonist (e.g., Noradrenaline, Adrenaline).
- “squeeze from peripheries” - gives time to investigate and treat underlying condition
- Clinical effects: Increased heart rate and force of contraction, vasoconstriction, and improved blood pressure.
- Other treatments: Antibiotics (and necessary checks including cultures and CXRs), fluids, sepsis management.
Describe the medications used to treat a 55 year old patient with new onset bronchospasm
- Beta 2 Adrenoreceptor to target: Agonist (e.g., Salbutamol).
- Clinical effects: Bronchodilation, increased heart rate, and possibly tremors.
- Possible causes: Allergic reaction, respiratory infection, environmental exposure, etc.
- Influence on acute treatment: Targeting bronchospasm with bronchodilators.
What would you use to treat peripheral vasoconstriction?
- use alpha1 agonists e.g. NA for peripheral vasoconstriction
What would you use to dilate bronchioles?
- beta 2 agonists for bronchodilation
and vasodilation
