The Drug Cabinet

Dr M Rughooputh
Nephrologist, JNH
25 June 2022
Topics covered

• Classes of HBP drugs

• Prescribing strategies
• RAASi use & stoppage
• Hyperkalemia
• Ethnicity, race and hypertension
• Other drugs and substances causing hypertension
 Introduction
• Primary goal: ↓CV morbidity/ mortality risk (proportional to BP control)

• Timing to start drugs: Grade 1 HBP with high risk (CVS, Kidney, DM, HMOD), all Grade 2 HBP

• If patient require more than 2 drugs, encourage bedtime dose

• Goal reached up to 3 months (<65yrs: 120-130/70-80 mmHg; >65yrs: <140/90 mmHg)
• Once BP control: yearly review (HMOD)
• Drug(s) dosage + lifestyle changes

• >80yrs: monotherapy favored

• Combination therapy: Synergistic and improved compliance

• Inter-individual variation in response

• Other drugs to be considered:

• Aspirin: primary prevention in >50 with 10 years CVS risk >20%; Secondary prevention in CV
diseases
• Statins: primary prevention if 10 years CVS risk > 20%; Secondary prevention in CV diseases
(aim total cholesterol <4mmol/L, LDL<2mmol/L)
Classes of anti-hypertensives
Class Mechanism of Compelling Caution Contraindications Remarks
action indications
Alpha blockers Block alpha BPH Post. Hypo, U. Incontinence
(prasozin, receptors, disabling heart failure
terazosin) vasoconstriction of
vessels
ACE Inhibitors Vasodilation HF, LV K esp. Renal Pregnancy, Prevent cardiac
Decrease dysfunction, impairment, renovascular remodeling
Intraglomerular post MI, DN, 2 angioedema, diseases Dysgeusia, cough
pressure prevent stroke PVD
Decrease
aldosterone and
ADH
ARBs Similar to ACE: ACEi Pregnancy, No cough
decrease SVR, SV intolerence renovascular Less angioedema
diseases
Beta- blockers Decrease HR and MI, angina, HF DM, PVD, Asthma, COPD,
SV Acute HF Heart Block
CCB Decrease SVR Elderly, ISH, *combination beta- palpitation, headache,
angina blockers flushing, and dizziness
Thiazide/T like Decrease SV Elderly, HF, 2 Gout
diuretics stroke
prevention
Other antihypertensive drugs
Diuretics
• K wasting
• Thiazide
• loop
• K sparing diuretics
• Epithelial sodium channel blockers: Amiloride, Triamterene
• Aldosterone antagonists: Spironolactone, Eplerenone, Finerenone

• Direct vasodilators: Hydralazine, minoxidil, sodium nitroprusside, diazoxide

• Central alpha 2 agonists: clonidine, methyldopa

• Adrenergic neurone blockers: Guaethidine

• Catecholamine depleters: Reserpine
• Ganglion blockers: Trimethaphan, Mecamylamine
• 5 HT antagonists: Ketanserin
Prescribing strategies

Escalate regime
Feedback from
BP control, side effects, tolerance

2020 International Society of Hypertension Global Hypertension Practice Guidelines

Thomas Unger, Claudio Borghi, Fadi Charchar, Nadia A. Khan, Neil R. Poulter, Dorairaj Prabhakaran, Agustin Ramirez, Markus
Schlaich, George S. Stergiou, Maciej Tomaszewski, Richard D. Wainford, Bryan Williams, Aletta E. Schutte
 2020 International Society of Hypertension Global Hypertension Practice Guidelines
Thomas Unger, Claudio Borghi, Fadi Charchar, Nadia A. Khan, Neil R. Poulter, Dorairaj Prabhakaran, Agustin Ramirez, Markus
Schlaich, George S. Stergiou, Maciej Tomaszewski, Richard D. Wainford, Bryan Williams, Aletta E. Schutte
 Special considerations
• Coronary Artery Disease (CAD): RAS blockers, beta-blockers irrespective of BP levels ± calcium channel blockers
(CCBs)
• Previous Stroke: RAS blockers, CCBs, and diuretics
• Heart Failure (HF): RAS blockers, beta-blockers, and mineralocorticoid receptor antagonists are all effective in
improving clinical outcome in patients with established HFrEF, whereas for diuretics, evidence is limited to symptomatic
improvement. CCBs are indicated on in case of poor BP control. Angiotensin receptor-neprilysin inhibitor (ARNI;
sacubitril-valsartan) is indicated for the treatment of HFrEF as an alternative to ACE inhibitors or ARBs also in
hypertensive populations. The same treatment strategy can be applied to patients with HFpEF
• Chronic Kidney Disease (CKD): RAS-inhibitors, CCBs and diuretics (loop-diuretics if eGFR <30 ml/min/1.73m2) can be
added.
• Chronic Obstructive Pulmonary Disease (COPD): angiotensin AT1-receptor blocker (ARB) and CCB ± diuretic, while
beta blockers (ß1-receptor selective) may be used in selected patients (eg. CAD, HF).
• HIV/AIDS: drug interaction with CCB under most of the antiretroviral therapies.
• Pregnancy: methyldopa, beta-blockers (labetalol), and dihydropyridine-calcium channel blockers (DHP-CCBs)
(nifedipine [not capsular], nicardipine). Contraindicated: RAS blockers (ACE-I, ARB, direct renin inhibitors
• Inflammatory Rheumatic Diseases (IRD): RAS-inhibitors (evidence of an overactive RAAS) and CCBs.
avoiding high doses of NSAIDs.
• Psychiatric Diseases: RAS-inhibitors and diuretics, CCBs and alpha1-blockers orthostatic hypotension (eg, SRIs).
Beta-blockers if drug-induced tachycardia (NOT metoprolol)
Why RAAS Inhibitors? Antiproteinuric effect
When to stop ACEi and ARBs?

K level

Serum creatinine level rise

above 30% over baseline
during the first 2 months
after initiation of therapy

Screen for RA Stenosis

Should Renin-Angiotensin System Blockade Be Avoided in Patients With Declining Kidney Function?
Matthew R. Weir, Debbie C. Chen, Elaine Ku Published: May 12, 2020
DOI:https://doi.org/10.1053/j.ajkd.2020.04.003
Tackling hyperkalemia
• Drugs affecting K: RAASi, Diuretics (thiazides, loop, K sparing), Beta Blocker, lack of insulin

Intracellular migration of K+ such as insulin and β-adrenergic stimulation (mainly a β2-adrenergic

effect)

• Pseudohyperkalemia: Prolonged use of a tourniquet above a venipuncture site or extended fist

clenching produces tissue hypoxia and promotes the escape of K+ from tissues into the plasma
compartment.

• Supplements of potassium with diuretics that block reabsorption of sodium and water upstream from
the distal tubule (thiazides and loop diuretics), because this promotes increased distal tubular
potassium secretion, with resultant increased potassium excretion

Calcium channel blockers increase the cellular uptake of K+ and has an inconsistently effect serum K+
concentrations at usual doses
Ethnicity, Race and Hypertension
Ethnicity (genetic differences), lifestyle and socioeconomic status and health behaviors such as diet

Populations From African Descent

• Develop hypertension and associated organ damage at younger ages, have a higher frequency of
resistant and nighttime hypertension, and a higher risk of kidney disease, stroke, HF, and mortality
• Increased cardiovascular risk: suppressed RAAS, altered renal sodium handling, increased
cardiovascular reactivity, and early vascular aging (large artery stiffness)
• Annual screening; Lifestyle modification (salt restriction, increased intake of vegetables and fruits, weight
management, reducing alcohol intake)
• First-line pharmacological therapy is recommended as a single pill combination including a thiazide-like
diuretic plus CCB or CCB plus ARB (angioedema is about 3 times more likely to occur with ACE
inhibitors)

Populations From Asia

• Hypertensive patients: greater salt-sensitivity accompanied with mild obesity.
• Higher prevalence of stroke (particularly hemorrhagic stroke) and non-ischemic HF
• Morning hypertension and nighttime hypertension are also more common in Asia, compared with
European populations.
• South Asian populations originating from the Indian subcontinent have a particularly high risk for
cardiovascular and metabolic diseases, including CAD and type 2 DM.
Drugs and substances causing hypertension
Recreational drugs
• Intoxication with;
• Amphetamines
• Sympathomimetic
• Cocaine

• Sympathetic hyperactivity: hypertensive emergency

• use of benzodiazepines should be considered prior to specific

antihypertensive treatment.

• Phentolamine, a competitive alpha-receptor blocking agent

• clonidine, a centrally sympatholytic agent with additional sedative
• Nicardipine
• Nitroprusside
Resistant Hypertension
• Resistant hypertension is defined as seated office BP >140/90 mm Hg in a
patient treated with three or more antihypertensive medications at optimal
(or maximally tolerated) doses including a diuretic.

• and after excluding pseudo-resistance (poor BP measurement technique,

white coat effect, non-adherence and suboptimal dose)

• Rework diagnosis: Secondary hypertension

Thank You