Drug MOA Effects Pharmacodynamics/ Clinical Application Toxicity/Toxicity Management
Pharmacokinetics
DIURETICS (lowers BP by depleting the body of Na+, and reducing Blood volume)
• After 6-8 weeks, CO returns toward normal while peripheral resistance declines
• Effective in lowering BP by 10-15 mmHg
• Severe cases of HPN, used in combination with sympathoplegic and vasodilator drugs to control the tendency toward Na retention First choice and cost effective
Thiazides Inhibit Na/Cl transporter in DCT Normal CO, but Peripheral Use in patients with mild to moderate • Hypokalemic Metabolic
HYDROCHOLOROTHIAZIDE resistance decreases hypertension with normal renal and Alkalosis
cardiac function • Hyperuricemia
• Impaired CHO tolerance
• Hyperlipidemia
• Hyponatremia
• Hypercalcemia
• Allergic reaction (sulfonamide
hypersensitivity) Photosensitivity
• Haemolytic anemia
• Thrombocytopenia
Loop Diuretics Inhibits NK2Cl Transporter in the thick -reduces blood volume without • Commonly used in patients with fluid • Hypokalemic metabolic alkalosis
FUROSEMIDE ascending loop inhibiting Na Cl decreasing peripheral vascular overload • Ototoxicity
- MOST POTENT reabsorption resistance. • Used in severe hypertension • Hyperuricemia
DIURETICS -loop diuretics increases urinary • Multiple drugs with Na-retaining • Hypomagnesemia
AVAILABLE water, Na+, K+, Calcium and propertiens are used • Skin rash, eosinophilia, interstitial
Magnesium excretion • Cardiac failure /cirrhosis nephritis
• Hypersensitivity
Potassium sparing Inhibit Na reabsorption (K+ & H+ - Limited natriuretic activity. • Useful both to avoid excessive potassium • Hyperkalemia
Diuretics Excretion in distal and Collecting depletion and to enhance natriuretic • Hyperchloremic Metabolic Acidosis
tubules) effects of other diuretics
• Hyperkalemia
DRUGS ALTERING SYMPATHETIC FUNCTION
- Moderate to severe hypertension: most effective drug includes an agent that inhibits function of the sympathetic nervous system
- Common adverse effects: sedation, mental depression, disturbances of sleep including nightmares. Lowering blood pressure by altering sympa function can have compensatory mechanism which is retention of sodium by the kidney and
expansion of blood volume
Are most efficient when taken concomitantly with a diuretic
CENTRALLY ACTING SYMPATHOPLEGIC DRUGS
(Lowers BP by reducing PERIPHERAL TOTAL VASCULAR RESISTANCE, (-) cardiac function, (-) increasing venous pooling in capacitance vessels)
- Reduces sympathetic outflow from vasomotor center in the brainstem but allowing these centers to retain sensitivity with the baroreceptor activity
Drug MOA Effects Pharmacodynamics/Pharma Clinical Uses Toxicity/Toxicity Management
cokinetics
1
, - Analog of L-Dopa and is converted - Lowers bp by reducing - Maximal MOST COMMON ADVERSE EFFECT:
METHYLDOPA to alpha-methyldopamine and peripheral vascular resistance antihypertensive effect: 4-6 INDICATIONS: Sedation at the onset of treatment Other
alpha-methylnorepinephrine with a variable reduction in hours -drug of choice for HYPERTENSION during adverse effects:
- Antihypertensive action due to heart rate and cardiac output - effects: persist pregnancy • REBOUND HYPERTENSION:
stimulation of central alpha - Cardiovascular reflexes up to 24 hours - Patients with renal insufficiency sudden cessation due to
adrenoreceptors by remain intact - highly CONTRAINDICATIONS: increased outflow-> increased
alphamethylnorepinephrine or - Decreases renal vascular dependent on accumulation 1.) LIVER DISEASE intensity
Alpha-adrenoreceptor
resistance and storage of metabolite
agonist alpha methyldopamine 2.) DIALYSIS PATIENTS • GI Symptoms: nausea,
alpha methylnorepinephrine
REVIEW! 3.) BLOOD DYSCRIASIS vomiting, diarrhea
in the vesicles of nerve
Alpha2 receptors-> 4.) OLDER ADULTS Long-term therapy: patients may complain
endings, its action diminish
decreases release of NTA after the parent drug has persistent
disappeared from the • mental lassitude and impaired
DRUG INTERACTIONS circulation mental concentration.
1.) LEVODOPA - half-life: 3-7 • Nightmares, mental depression,
2.) LITHIUM hours vertigo & extrapyramidal signs may
3.) NSAIDs, TRICYCLICS, - Bioavailability: exist.
25%
SYMPATOMIMETICS • Lactation for both man and woman
Increased BP probably mediated by inhibition of
dopaminergic mechanism
• Developing a positive COOMBS
TEST:
makes cross-matching blood for
transfusion difficult and rarely
associated with haemolytic anemia,
hepatitis and drug fever
CLONIDINE (CATAPRES) • Bind more tightly to α2 receptors -decreased NTA release-> - Lipid soluble INDICATIONS: -rarely causes postural hypotension -
• Derivative of than α1 decreased - Rapidly enters the • HPN severe hypotension can complicate
2imidazoline • Decreased sympathetic effects catecholamines>decreased brain from the • Nicotine/opiate withdrawal overdose.
• EMERGENCY DRUG in and increases parasympathetic sympa effects circulation • Vascular headaches Abrupt withdrawal can cause
tone-> low blood pressure and - lowers BP by - Short half life lifethreatening hypertensive crisis:
HTN CRISIS. As • Glaucoma
bradycardia decreasing heart rate and relaxation - Oral clonidine must be REBOUND HPN.
needed medication • Ulcerative colitis
(impeding stroke, • Binds to a non-adrenoreceptor site of capacitance vessels and (nervousness, tachycardia, headache and
given 2x a day • Tourette’s syndrome
chest pain) we need decreased in PVR - reduction in sweating)
(IMIDAZOLINE RECEPTOR)-> • Severe pain in CA patients
arterial BP-> decreased renal - Withdrawal should be done gradually
to lower it gradually Mediate antihypertensive effects
vascular resistance and with other antihypertensive agents
maintenance of renal blood flow substituted
- More effective in - Treatment:
decreasing heart rate and cardiac Administration of alpha and beta
output than methyldopa adrenoreceptor blocking agents TOXIC
Guanabenz, Gunfacine are alpha EFFECTS:
adrenoreceptor agonist
• Dry mouth
• Sedation
CONTRAINDICATIONS:
• Px who are at risk for developing
mental depression
• Concomitant treatment with
tricyclic antidepressants
2
Pharmacokinetics
DIURETICS (lowers BP by depleting the body of Na+, and reducing Blood volume)
• After 6-8 weeks, CO returns toward normal while peripheral resistance declines
• Effective in lowering BP by 10-15 mmHg
• Severe cases of HPN, used in combination with sympathoplegic and vasodilator drugs to control the tendency toward Na retention First choice and cost effective
Thiazides Inhibit Na/Cl transporter in DCT Normal CO, but Peripheral Use in patients with mild to moderate • Hypokalemic Metabolic
HYDROCHOLOROTHIAZIDE resistance decreases hypertension with normal renal and Alkalosis
cardiac function • Hyperuricemia
• Impaired CHO tolerance
• Hyperlipidemia
• Hyponatremia
• Hypercalcemia
• Allergic reaction (sulfonamide
hypersensitivity) Photosensitivity
• Haemolytic anemia
• Thrombocytopenia
Loop Diuretics Inhibits NK2Cl Transporter in the thick -reduces blood volume without • Commonly used in patients with fluid • Hypokalemic metabolic alkalosis
FUROSEMIDE ascending loop inhibiting Na Cl decreasing peripheral vascular overload • Ototoxicity
- MOST POTENT reabsorption resistance. • Used in severe hypertension • Hyperuricemia
DIURETICS -loop diuretics increases urinary • Multiple drugs with Na-retaining • Hypomagnesemia
AVAILABLE water, Na+, K+, Calcium and propertiens are used • Skin rash, eosinophilia, interstitial
Magnesium excretion • Cardiac failure /cirrhosis nephritis
• Hypersensitivity
Potassium sparing Inhibit Na reabsorption (K+ & H+ - Limited natriuretic activity. • Useful both to avoid excessive potassium • Hyperkalemia
Diuretics Excretion in distal and Collecting depletion and to enhance natriuretic • Hyperchloremic Metabolic Acidosis
tubules) effects of other diuretics
• Hyperkalemia
DRUGS ALTERING SYMPATHETIC FUNCTION
- Moderate to severe hypertension: most effective drug includes an agent that inhibits function of the sympathetic nervous system
- Common adverse effects: sedation, mental depression, disturbances of sleep including nightmares. Lowering blood pressure by altering sympa function can have compensatory mechanism which is retention of sodium by the kidney and
expansion of blood volume
Are most efficient when taken concomitantly with a diuretic
CENTRALLY ACTING SYMPATHOPLEGIC DRUGS
(Lowers BP by reducing PERIPHERAL TOTAL VASCULAR RESISTANCE, (-) cardiac function, (-) increasing venous pooling in capacitance vessels)
- Reduces sympathetic outflow from vasomotor center in the brainstem but allowing these centers to retain sensitivity with the baroreceptor activity
Drug MOA Effects Pharmacodynamics/Pharma Clinical Uses Toxicity/Toxicity Management
cokinetics
1
, - Analog of L-Dopa and is converted - Lowers bp by reducing - Maximal MOST COMMON ADVERSE EFFECT:
METHYLDOPA to alpha-methyldopamine and peripheral vascular resistance antihypertensive effect: 4-6 INDICATIONS: Sedation at the onset of treatment Other
alpha-methylnorepinephrine with a variable reduction in hours -drug of choice for HYPERTENSION during adverse effects:
- Antihypertensive action due to heart rate and cardiac output - effects: persist pregnancy • REBOUND HYPERTENSION:
stimulation of central alpha - Cardiovascular reflexes up to 24 hours - Patients with renal insufficiency sudden cessation due to
adrenoreceptors by remain intact - highly CONTRAINDICATIONS: increased outflow-> increased
alphamethylnorepinephrine or - Decreases renal vascular dependent on accumulation 1.) LIVER DISEASE intensity
Alpha-adrenoreceptor
resistance and storage of metabolite
agonist alpha methyldopamine 2.) DIALYSIS PATIENTS • GI Symptoms: nausea,
alpha methylnorepinephrine
REVIEW! 3.) BLOOD DYSCRIASIS vomiting, diarrhea
in the vesicles of nerve
Alpha2 receptors-> 4.) OLDER ADULTS Long-term therapy: patients may complain
endings, its action diminish
decreases release of NTA after the parent drug has persistent
disappeared from the • mental lassitude and impaired
DRUG INTERACTIONS circulation mental concentration.
1.) LEVODOPA - half-life: 3-7 • Nightmares, mental depression,
2.) LITHIUM hours vertigo & extrapyramidal signs may
3.) NSAIDs, TRICYCLICS, - Bioavailability: exist.
25%
SYMPATOMIMETICS • Lactation for both man and woman
Increased BP probably mediated by inhibition of
dopaminergic mechanism
• Developing a positive COOMBS
TEST:
makes cross-matching blood for
transfusion difficult and rarely
associated with haemolytic anemia,
hepatitis and drug fever
CLONIDINE (CATAPRES) • Bind more tightly to α2 receptors -decreased NTA release-> - Lipid soluble INDICATIONS: -rarely causes postural hypotension -
• Derivative of than α1 decreased - Rapidly enters the • HPN severe hypotension can complicate
2imidazoline • Decreased sympathetic effects catecholamines>decreased brain from the • Nicotine/opiate withdrawal overdose.
• EMERGENCY DRUG in and increases parasympathetic sympa effects circulation • Vascular headaches Abrupt withdrawal can cause
tone-> low blood pressure and - lowers BP by - Short half life lifethreatening hypertensive crisis:
HTN CRISIS. As • Glaucoma
bradycardia decreasing heart rate and relaxation - Oral clonidine must be REBOUND HPN.
needed medication • Ulcerative colitis
(impeding stroke, • Binds to a non-adrenoreceptor site of capacitance vessels and (nervousness, tachycardia, headache and
given 2x a day • Tourette’s syndrome
chest pain) we need decreased in PVR - reduction in sweating)
(IMIDAZOLINE RECEPTOR)-> • Severe pain in CA patients
arterial BP-> decreased renal - Withdrawal should be done gradually
to lower it gradually Mediate antihypertensive effects
vascular resistance and with other antihypertensive agents
maintenance of renal blood flow substituted
- More effective in - Treatment:
decreasing heart rate and cardiac Administration of alpha and beta
output than methyldopa adrenoreceptor blocking agents TOXIC
Guanabenz, Gunfacine are alpha EFFECTS:
adrenoreceptor agonist
• Dry mouth
• Sedation
CONTRAINDICATIONS:
• Px who are at risk for developing
mental depression
• Concomitant treatment with
tricyclic antidepressants
2
