Pharmacology Of Antihypertensives Flashcards
AHA and WHO definitions of hypertension
AHA: 140/90
WHO: 160/95
Hypertension diagnostic criteria
Two or more readings greater than normal at least 2-4 weeks apart
Two types of hypertension and their prevalence
Essential/primary = 90%: idiopathic, genetic basis for incidence most often found in middle-aged adults Non-essential/secondary = 10%: clinically identifiable cause
Therapy choices for HTN depend on what kind of factors? (9)
- Age
- Ethnicity (37-40% African American men and women are currently being treated for HTN and 25% of US citizens overall are being treated for HTN)
- Body-type
- Obesity
- Personality type
- Athletic or sedentary lifestyle
- Etiology of HTN
- Rapidity of onset and severity
- Presence of other risk factors for CV disease
Lifestyle modifications for HTN management (8)
- Weight loss
- Limit alcohol intake (less than 1 oz per day)
- Aerobic physical activity (30-45 min per day)
- Reduce Na+ intake to less than 100mmol (6g) per day
- Maintain intake of K+ to 90mmol (7g) per day
- Maintain intake of Ca2+ and Mg2+
- Smoking cessation
- Reduce dietary sugar, saturated fat, and cholesterol intake
HTN considerations for patients (5)
- Once initiated, treatment is usually for life
- Financial cost
- Dosage should be carefully considered due to side effects and drug interactions
- Patient compliance
- Consider the Step-Care Therapy approach
Step Care Therapy (4)
- Lifestyle Modifications
- ACEI/ARB
- higher drug dose/substitute for another drug/add second drug
- second or third agent (at least one should be a diuretic)
For each agent considered for HTN management, you must also consider what?
The baroreceptor reflex!
The baroreceptor reflex does what?
Attemps to lower pressure activates reflex mechanisms that then act to raise the pressure: Na+ and H2O retention by the kidneys, sympathetically-induced increases in peripheral vascular resistance, heart rate, and cardiac output.
Diuretics (General, MOA, Efficacy)
General: Includes thiazides, loop diuretics, K+-sparing diuretics.
MOA: Relatively unknown. Appears to decrease blood volume resulting in a decrease in CO.
Indapamide also has direct vasodilating properties.
Efficacy: Moderate monotherapy, 20/10, but augments antihypertensive effects of other drugs. Greater efficacy in African-Americans and elderly patients.
Diuretics (Pharmacokinetics, ADRs, Contraindications)
PK: Taken PO with onset of action in 2-4 weeks; peak effects in 3-4 months. No additional efficacy from increased dosage, but incidence and severity of ADRs increase.
ADRs:
- Hyperuricemia
- Hypokalemia
Contraindications:
- Diabetes (may induce hyperglycemia)
- Hyperlipidemia (tend to elevate LDL and triglycerides)
Beta-adrenergic antagonists [Beta Blockers] (General, MOA, Efficacy)
General: Propranolol (competitive, non-selective beta receptor antagonist)
MOA: Blocks beta-1 and beta-2 receptors. Decreases HR and contractility to decrease BP. Also decreases renin release and angiotensin II formation.
Efficacy: Moderate in monotherapy, better in combination therapy. Smokers respond poorly to these agents.
Beta-adrenergic antagonists [Beta Blockers] (Pharmacokinetics, ADRs, and Considerations)
PK: PO/IV, lipophilic (wide distribution), extensive first-pass metabolism with production of active metabolites
ADRs: 7-9% of patients discontinue use
- Minor GI and CNS nausea
- Asthma exacerbation
- Hyperlipidemia (increases triglycerides and lowers HDL)
- Male sexual dysfunction
- Diabetes (masks signs and symptoms of hypoglycemia which may lead to increased incidence of coma and death)
- CHF exacerbation
Considerations (labetalol and carvedilol):
- Block beta-1, beta-2, alpha-1
- Very good efficacy in lowering BP especially in presence of HF
- PO for long-term management of CHF and HTN; IV for HTN emergencies
Centrally-acting Sympatholytics [Clonidine] (General, MOA, Efficacy)
General: Clonidine has a number of clinical uses
MOA: Post-synaptic alpha-2 agonist in CNS - inhibits sympathetic outflow at the level of the NTS resulting in decreased HR and TPR. Acts upon presynaptic alpha-2 agonists in the periphery - decreased NE release from postganglionic nerve terminals.
Efficacy: 35/20, monotherapy (combination with a diuretic is common).
Centrally-acting Sympatholytics [Alpha-Methyldopa] (General, MOA, ADRs)
General: Analog of DOPA, converted in CNS neurons to alpha-methylnorepinephrine
MOA: Stimulates inhibitory presynaptic alpha-2 receptors. Acts as “false transmitter” at post-synaptic terminals. Drug choice for treatment of chronic HTN in women during child-bearing years.
ADRs:
- Prominent sexual dysfunction
- Dry mouth
- Sedation
- Positive direct Coombs test producing frank hemolytic anemia