8/23/20

Introduction to Pharmacology is the study of drugs.

Pharmacology
Manuelito P. Talaue Jr., RPh. MSc. ©

1 2

Functional Classes Of
Drugs
1. Functional modifies
Drugs
- after of modify activity of body cells
Any article used in the DMTCP of disease in man and animals
Modifies the body structure and function
Examples:
Analgesics – modify pain perception

3 4

Functional Classes Of Drugs Functional Classes Of

Replenishers Drugs
- Supplements endogenous compounds that are insufficient of
looking Chemotherapeutic Agents
- Agents that inhibit the growth or kill
cells/nucleic acids that are foreign to the
Examples: body
Insulin
Vitamin Deficiency
Examples:
Anti-neoplastic agents
Anti-infectives

5 6

1
Functional Classes Of Drugs
Diagnostic Agents
Edrophonium (Tensilon)
Radiopharmaceuticals

Radiopharmaceutica Functions
ls
Technetium 99m-Phytate Liver imaging
Technetium 99m- Renal function/ kidney
Heptagluconate
Technetium 99m-HIDA Hepatobiliary function
Technetium 99m-Etidronate Bone imaging
Technetium 99m-Na Brain, thyroid and
perthechnetate gastrointestinal imaging
7 8

Radiopharmaceuticals Functions Radiopharmaceuticals Functions

I-131 Human Serum Determines Blood plasma Sodium phosphate
Albumin volume Sodium chromate Cr51
Sodium Iodide I1-25 Thyroid functions injection
Sodium Iododppurate 1131 Renal function Cyanocobalamine Co57
Selenomethionine Se 75 For diagnosis of pancreatic injection
cancer Chlormerodrin Hg 197

9 10

Divisions of Pharmacokinetic
Pharmacology
1. Pharmacokinetics
Pathways
2.
Pharmacodynamics

11 12
Pathways Absorption
Absorption Distribution Metabolism Excretion It is the transfer of a drug from its site of
administration to the systemic circulation

13 14

Factors Affecting Absorption

Gastric Emptying Time
Chemical structure
Longer
Gastric Emptying Time
Shorter
Variation in particle size (VS SA)
Nature of the crystal form
Blood flow to the absorption site
Total surface area available for absorption surface
Contact time at the absorption site

15 16

Transport Mechanisms Passive Diffusion

It is the process by which molecules spontaneously diffuse
A. Passive Diffusion from a region of higher concentration to a region of lower
concentration
B. Convective Pore Transport
Examples:
C. Active Transport
Weak Organic Acids
D. Facilitated Diffusion
Weak Organic Bases
E. Ion-pair
Cardiac Glycosides
F. Vesicular Transport

17 18
Active Transport Facilitated Diffusion
The movement of drug molecule is from lower concentration A carrier-mediated transport system
to higher concentration
It moves along the concentration gradient

Examples
Minerals
Sugars
Amino acids

19 20

Convective Pore Transport Vesicular Transport

Movement of a compound across membranes by way of passages It is the process of engulfing particles or dissolved materials
between the cells by the cell
Drug transport across tight (narrow) junctions between cells or trans Endocytosis
endothelial channels of cells
Phagocytosis
Examples: Pinocytosis (ADEK, fats, glycerin, insulin)
Inorganic and Organic electrolytes up to 150-400 MW
Ions of opposite charge of pore lining
Ionized sulfonamides

21 22

Bioavailability Distribution
It is the fraction of administered drug that It is the process by which a drug reversible leaves the blood
stream and enters the interstitium (extracellular fluid) and/or
reaches the systemic circulation in a chemically
the cell of the tissues
unchanged form

23 24
Protein Binding Site Metabolism
Albumin
To supply energy for body functions and
Alpha-acid glycoprotein maintenance
Globulin Plays central role in the elimination of the drugs
Lipoproteins and xenobiotics(foreign compounds)
RBC Converts drug into polar, water soluble, ionized
form that are readily
excreted

25 26

Factors
Age
Race
Gender
Individual variations
Enterohepatic circulation
Nutrition
Intestinal flora

27 28

Prodrugs Prodrugs
These are compounds that are inactive in their native The term prodrug was first coined by Albert in
form, but are easily metabolized to the active agent 1958.
Harper (1959) defines this as the chemical
modifications of a biologically activity compound
to form a new chemical entity.

29 30
 Example: Clindamycin Example: Barbiturates
There is poor patient compliance for Clindamycin Increase affinity to adipose tissue compound to
have sedative hypnotic effect.

31 32

Drugs that are

First-Pass Effect metabolized
Drugs may be metabolized by hepatic enzyme to extensively by 1st pass
inactive chemicals (drug is metabolized prior to effect:
absorption)
Isoproterenol
Morphine
Propoxyphene
Lidocaine
Nitroglycerin
Propranolol
Meperidine
Pentazocine
Salicylamide
33 34

Extrahepatic Metabolism
Isoproterenol and Levodopa Phase 1
Esterase and Lipases Metabolism
Bacterial Flora
Intestinal B-glucoronidase

35 36
 Phase I Metabolism Phase II Metabolism
It is also known as /

3 Processes
1.
2.
3.

37 38

Phase II Metabolism Conjugation Reactions

It is also known as Reactions involved:
Glucoronic Acid Conjugation
/ Sulfate Conjugation
Acetylation
Methylation
Glutathione or Mercaptupuric Conjugation

39 40

Elimination Renal
Routes: Glomerular Filtration
Ionized and non-ionized forms of drugs are filtered, but
Kidney Bile Intestine Lung protein-bound drug molecules are not.
Milk of nursing mother
Proximal Tubular Secretion Carrier mediated, active
transport Distal Tubular Reaqtion Passive diffusion
Non-ionized and lipophilic are reabsorbed

41 42
 Key Terms
Drug
Pharmacodynamics An agent intended for use in the diagnosis, mitigation,
treatment or prevention of disease in humans or in
animals
Receptor
A substance to which a drug needs to interact with the
drug molecule

43 44

Receptor
Affinity
Relatively small region of a macromolecule May be Ability of a drug to bind
a/an: with a receptor
Enzyme
Structural functional group Intrinsic
Specific intracellular substance such as proteins Activity
and nucleic acids Ability of a drug
to exert a
pharmacologic
action
45 46

Antagonist
Agonist Drug with affinity but does not have
intrinsic property
Drug with affinity and intrinsic
They bind to regions of the receptor
activity that are not involved in binding the
natural ligand
Antagonist
Drug with affinity but no intrinsic
activity

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Sensitization Desensitization
Occur when an antagonists is bound to a receptor for This condition may occur when an agonist is bound to its
a long period of time. receptor for a long period of time
The cell synthesizes more receptor for a long period of Tolerance
time It is a situation where increase doses of a drug are required
over time to achieve the same effect
Dependence
It refers to the body’s ability to adapt to the presence of the
drug

49 50

Efficacy
It is determined by measuring the maximum
possible effect resulting from receptor ligand
binding
Potency
Relates how effective a drug is in producing a
cellular effect

51 52

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Autonomic Nervous
System
Prepared by: Manuelito P. Talaue Jr.

1 2

Differences Between the Somatic and

Autonomic Nervous System

Somatic Nervous System Autonomic Nervous System

Anatomy 1 neuron set-up 2 neuron set-up
Ganglion  collection of neuron’s
cell bodies located
outside the CNS (an exclusive
feature of ANS)
Functional Voluntary Movement Involuntary Movement Ex.
Ex. Contraction of the Skeletal Heartbeat, Contraction of
Muscle the e blood vessels, sweat
glands

3 4

Synaptic Neurotransmission
• Transmission of neural impulses
Pre-synapse  synaptic cleft  post-synapse

5 6

2
 Sympathetic VS Parasympathetic Nervous
System

Origin Receptors Neurotransmitter

Parts of
the
Spine
Cranial (Cervical) Parasympathetic N, M Acetylcholine

Sacral Parasympathetic N, M Acetylcholine

Thoracic Sympathetic A, B, D Catecholamines

7 8

9 10

Sympathetic Nervous Parasympathetic Nervous

System System
Eye
Pupils Dilation Constricts (Near
Ciliary Muscles (Far Vision) Vision)
Bronchial Smooth Muscles Bronchodilation Bronchoconstriction

Heart (+) Inotropic (-) Inotropic

(+) Chronotropic (-) Chronotropic
GIT
Sphincters Closed Opened
Intestinal Wall Muscles ↓ Motility ↑ Motility
Secretions ↓ ↑
Bladder
Sphincter Wall Closed Opened
Muscles Relaxed Contraction

11 12
 Sympathetic Nervous Parasympathetic Nervous
System System
Male Genitalia Ejaculation Erection
Uterus Relaxation Contraction
Salivary Glands Thick, viscid secretion Copious, watery secretion
Lacrimal Glands Secretion
Skin A. Sympathetic Nervous System
Pilimotor Smooth Muscles Contraction Prepared by: Manuelito P. Talaue Jr.
Sweat Glands ↑ Sweating
Skeletal Muscles Relaxation Contraction
Metabolic Functions
Liver Gluconeogenesis Glycogenolysis

Fat Cells Lipolysis

Kidneys Renin Release

13 14

15 16

Receptors Alpha-1 Receptors

• Alpha-1 Location: Blood
Vessels Eyes
• Alpha-2
Piloerector Muscles
• Beta-1
Urinary Bladder
• Beta-2
• Beta-3

• Dopamine (1, 2, 3, 4)

17 18
 Alpha-2 Receptors Beta-1 Receptors
Location: Location:
Presynaptic Heart Kidney
Post-synaptic

19 20

Beta-2 Receptors Dopamine Receptors

Location: Location:
Lungs D1  Increased Urination

Uterus D2-D4  Nausea, Vomiting due to loss of

peristalsis Stomach Distention

Potassium Level

21 22

A. Sympathetic Agonist
Sympathetic Nervous System
A.A. Direct Acting
Selective
• Agonist Non-selective

• Antagonist
A.B. Indirect Acting

A.C. Centrally Acting

23 24
 A.A.1. Non-selective direct-acting agonist A.A.2. Selective direct-acting agonist
• Epinephrine (a1=a2, B1=B2) • Selective to a1 receptors
• Phenylephrine
• Norepinephrine (a1 > a2, B1 > B2) • Oxymetazoline
• Tetrahydrozoline
• Dopamine • Propylhexedrine
• Methoxamine
• Isoproterenol (Partially)

25 26

A.A.2. Selective direct-acting agonist A.A.2. Selective direct-acting agonist

• Selective to a2 receptors • Selective to B1 receptors
• Clonidine • Dobutamine

• Methyldopa

27 28

A.A.2. Selective direct-acting agonist

• Selective to B2 receptors
A.B.1. Indirect-acting
• LABA
• Formoterol MOA
• Bambuterol
• Salmeterol Release norepinephrine
• SABA
• Salbutamol Inhibit re-uptake of norepinephrine
• Terbutaline

29 30
 B. Sympathetic Antagonist
A.C.1. Centrally Acting
B.A. Alpha Blockers
Non-selective
Phenylpropanolamin Selective

e Methylphenidate
B.B. Beta Blockers
Amphetamine Non-Selective
Selective
ISA
Phentermine MSA
Mixed

Phenmetrazine

31 32

B.A.1. Non-selective alpha blockers

B.A.2. Selective Alpha blockers
• Phenoxybenzamine - Irreversible
• Phentolamine • Alpha-1 Blockers
• Prazosin, Doxazosin, Terazosin, Alfuzosin, Tamsulosin

• Alpha-2 Blockers
• Yohimbine and Rauwolscine

33 34

ALPHA BLOCKERS USES Beta Blockers

Non-Selective Selective
• Pheochromocytoma Nadolol Nebivolol
Sotalol Bisoprolol
• Reynaud’s Syndrome Timolol Betaxolol
Propranolol Esmolol

• Hypertension and Urinary Retention in BPH Pindolol Acebutolol

Atenolol

• Erectile Dysfunction Metoprolol

• Carcinoid Syndrome

35 36
 Beta Blockers BETA BLOCKERS USES
• Hypertension
• Angina Pectoris
Membrane Stabilizing Activity
• Stable Heart Failure
Intrinsic • Arrhythmia
Sympathomim
• Glaucoma
etic Activity
Carteolol
Labetalol
Propranolol
Pindolol
• Sympathetic Symptoms of Hyperthyroidism
Acebutolol Acebutolol
• Stage Fright
37 38

B. Parasympathetic Nervous System

Prepared by: Manuelito P. Talaue Jr.

39 40

Receptors Muscarinic 1 (M-1)

• M-1 • Parietal Cells in the Stomach
• M-2
• M-3
• Nicotinic

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 Muscarinic 2 (M-2) Muscarinic 3 (M-3)
• Heart • Eyes
• Lungs
• Stomach Muscles
• Penis
• Sweat Glands
• Urinary Bladder

43 44

A. Parasympathetic Agonist
Nicotinic Receptors
A.A.Direct-acting
Choline Esters
• Nn Alkaloids
• Nm
A.B. Indirect Acting
Reversible
Irreversible

45 46

A.A.1. Choline Esters (Direct Acting)

A.A.2. Alkaloids (Direct Acting)
• Carbachol
• Nicotinic
• Acetylcholine
• Nicotine
• Metacholine • Lobeline
• Varenicline
• Betanechol • Muscarinic
• Muscarine
• Pilocarpine

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 9/26/20

A.B.1. Reversible A.B.2. Irreversible

• Physostigmine • Organophospahtes
• Neostigmine • Parathion and Malathion
• Edrophonium • Tabun, Sarin, Soman
• Demecarium
• Rivastigmine
• Tacrine
• Donepezil
49 50

Parasympathetic Antagonist
B.A.1. Muscarinic Blockers
Muscarinic Blockers
• Atropine
• Scopolamine
• Biperiden
Nicotinic Receptor Blockers • Benztropine
Non-depolarizing • Trihexyphenidyl
Depolarizing • Cyclopentolate
• Homatropine
• Tropicamide
• Ipratropium
• Tiotropium
• Oxytropium

51 52

1
 9/26/20

Hypertension
Hypertension uHypertension is the most common cardiovascular disease. In a survey carried out in
2007/2008, hypertension was found in 29%of American adults.
Manuelito P. Talaue Jr., RPh. u The prevalence varies with age, race, education, and many other variables. According
to some studies,60–80% of both men and women will develop hypertension by age 80.
u Sustained arterial hypertension damages blood vessels in kidney, heart, and brain and
leads to an increased incidence of renal failure, coronary disease, heart failure, stroke,
and dementia.

1 2

Hypertension HypertensionandRegulation of Blood

Pressure
u Hypertension is defined conventionally as a sustained increase in blood
pressure 140/90 mm Hg, a criterion that characterizes a group of patients
whose risk of hypertension-related cardiovascular disease is high enough to
merit medical attention.
u Persistently elevated arterial blood pressure.

3 4

TABLE 1: JNC 8’S BLOOD PRESSURE GOALS Blood Pressure SYSTOLIC mmHg DIASTOLIC mmHg (lower
Category (upper number) number)
Population Start antihypertensive drugs when Target BP

HypertensionandRegulation of Blood
this parameter meets or exceeds
HypertensionandRegulation of Blood
NORMAL LESS THAN 120 And LESS THAN 90

ELEVATED 120 – 129 And LESS THAN 80

Pressure
SBP (mm Hg) DPB (mm Hg) SBP/DPB Pressure HIGH BLOOD
PRESSURE 130 – 139 Or 80 – 90
General population 60 years and older* 150 90 <15090 (HYPERTENSION)
STAGE1
General population 60 years and younger* 140 90 <14090 HIGH BLOOD
PRESSURE 140 or HIGHER Or 90 OR HIGHER
Adult with diabetes* or CKD* 140 90 <14090 (HYPERTENSION)
STAGE2

5 6

2
Etiology Primary Hypertension

uPrimaryHypertension u There is no identifiable cause

u Majority of the cases
uSecondary Hypertension
uHypertension in Pregnancy
uHypertensive Urgency
uHypertensive Emergency

7 8

Secondary Hypertension Hypertension in Pregnancy

u With an identifiable cause u Hypertension at the beginning of pregnancy

u Pre-eclampsia
u Eclampsia

9 10

Hypertensive Urgency Hypertensive Emergency

u DBP <- 120mmHg u Symptomatic and with Organ Damage

11 12
Predisposing Factors in Primary Normal Regulation of Blood Pressure
Hypertension
u Smoking
u Hyperlipidemia
BP= CO x PVR
u Diabetes Mellitus
u Family History of Cardiovascular Disease
u Age
u Obesity

u Stress
u Sedentary Lifestyle

13 14

Cardiac Output Systemic Vascular Resistance or SVR

Also known as the Total Peripheral Resistance/Peripheral Vascular Resistance/
Afterload
Formula: SV x HR Defined as the pressure required by the blood to be ejected by the heart

Factors that affect SV (Stroke Volume) Factor: Tone of the Arteries

Inotropism Arteriolar Vasoconstriction:
Preload

15 16

Mechanisms of Blood Pressure Regulation

Sympathetic Nervous System
-Baroreceptor Reflex Arc
RAAS
Fluid Retention
Mosaic Theory

17 18
Cardiac Effects Renal Effects
COMPLICATIONS

COMPLICATIONS
Angina Pain Polyuria
Left Ventricular Hypertrophy Nocturia
Edema of Extremeties Diminished ability to concentrate urine
Presence of RBC in the urine
Elevated Serum Creatinine

19 20

Cerebral Effects Retinal Effects

COMPLICATIONS

COMPLICATIONS

Transient Ischemic Attacks Visual Defects

Cerebral Thromboses Spots
Aneurysms with Hemorrhage
Blindness

21 22

Antihypertensive Agents
DIURETICS
VASODILATORS
PERIPHERAL SYMPATHOLYTICS
ANGIOTENSIN MODIFIERS
SYMPATHOPLEGIC AGENTS

23 24
DIURETICS
1. THIAZIDE DIURETICS
2. CARBONIC ANHYDRASE INHIBITORS First agent tried for mild hypertension and affect
3. LOOP DIURETICS blood sodium level

DIURETICS
4. POTASSIUM SPARING DIURETICS Lowers blood pressure
5. OSMOTIC DIURETICS

25 26

27 28
Thiazide Diuretics
DIURETICS

DIURETICS

Thiazide-Like Diuretics

Major Site of Action: Distal Convulated Tubules

DIURETICS

29 30
 Thiazide Diuretics
DIURETICS

Pharmacokinetics
1.Chlorthiazide 2.Hydrochlorothiazide 3.Chlorthalidone

DIURETICS
31 32

Thiazide Diuretics Thiazide Diuretics

1. Increase excretion USES:
Water, Sodium, Chloride, Potassium and Bicarbonate Mild to moderate hypertension with normal renal and cardiac
function
DIURETICS

DIURETICS

1. Decrease excretion
Calcium and Uric Acid CHF
Nephrolithiasis due to hypercalciuria
Nephrogenic Diabetes Insipidus

33 34

Thiazide Diuretics Thiazide Diuretics

ADVERSE EFFECTS: DRUG INTERACTIONS:
1. Hypokalemic Metabolic Alkalosis 1. Cholestyramine and Colestipol
2. Hyponatremia
DIURETICS

DIURETICS

3. Hypercalcemia
4. Hyperuricemia
5. Hyperglycemia
6. Hyperlipidemia
7. Allergic Reactions

35 36
Loop Diuretics Loop Diuretics
Major Site of Action
1.Thick Ascending Loop of Henle
DIURETICS

DIURETICS
37 38

Loop Diuretics
DIURETICS

USES:
Drug of choice when rapid and extensive diuresis is needed
DIURETICS

Reservedrugsforhypertensive emergencies and crisis

It is also a diuretic for patients with CHF

39 40

Loop Diuretics Loop Diuretics

USES: ADVERSE EFFECTS:
1. Hypokalemic Metabolic Alkalosis
1.Acute Pulmonary Edema 2.Acute hypercalcemia 3.For
2. Ototoxicity
DIURETICS

DIURETICS

hyperkalemia 4.Acute Renal Failure 5.Anion Overdose 3. Hyperuricemia

4. Hypomagnesemia
5. Allergic Reactions

41 42
Loop Diuretics Potassium-Sparing Diuretics
DRUG INTERACTIONS:
Aminoglycosides
Cisplatin
DIURETICS

DIURETICS
43 44

Potassium-Sparing Diuretics Mechanism of Action:

1.It prevents K+ secretion by antagonizing the effects of aldosterone at
the late distal and cortical collecting tubules
Major Site of Action
1.Late Distal and Cortical Collecting Tubules
DIURETICS

45 46

Potassium-Sparing Diuretics Potassium-Sparing Diuretics

2 Categories A. Spironolactone
Direct pharmacologic antagonism of mineralocorticoid receptor Adjunct drug in the management of CHF
DIURETICS

DIURETICS

By inhibition of Na+ influx through ion channels in the luminal Used in Conn’s Syndrome
membrane Structural analog of Aldosterone
Metabolized in the Liver and Absorbed in the GIT

47 48
 Potassium-Sparing Diuretics Potassium-Sparing Diuretics

Spironolactone Spironolactone’s ADVERSE EFFECTS

Specifically, it induces diuresis; Hyperkalemia
DIURETICS

DIURETICS
In patients with, hyperaldosteronism Hyperchloremic metabolic acidosis
Aldosterone producing adenomas Menstrual abnormalities in women
Gynecomastia,impotence,benign prostatic hyperplasia

49 50

Potassium-Sparing Diuretics
DIURETICS

DIURETICS

Potassium-Sparing Diuretics
B. Amiloride and Triamterene
B. Eplerenone
Onset of Action  2-4 hours
Spironolactone analog
MOA:
Decrease membrane permeability and inhibit
51 52 enic absorption of sodium and excretion of
electrog
potassium in the collecting tubule which is independent
of the presence of mineralocoticoid

Mechanism of Action:
OSMOTIC Diuretics 1. They are easily filtered and poorly reabsorbable solutes that alter the
diffusion of water relative to sodium by binding with water
Mannitol
2. They pull water into the renal tubules without sodium loss
Glycerin
DIURETICS

Isosorbide
Urea

53 54
Osmotic Diuretics Osmotic Diuretics
Major Site of Action USES
1.Proximal tubules and descending limn of loop of henle’s Increase urine volume
DIURETICS

DIURETICS
To reduce intracranial and intraocular pressure

55 56

Osmotic Diuretics Osmotic Diuretics

A. Mannitol Mannitol’s Adverse Effects
Given intravenously for prophylaxis of acute renal failure Expansion of the extracellular volume
resulting from trauma or surgery
DIURETICS

DIURETICS

Dehydration and hypernatremia

It increases blood volume and causes N/V

57 58

Carbonic Anhydrase Inhibitors (CAI) Diuretics

Osmotic Diuretics
Isosorbide and Glycerin
They are used in ophthalmic procedures
DIURETICS

DIURETICS
59 60
Carbonic Anhydrase Inhibitors (CAI) Diuretics Mechanism of Action:
Major Site of Action: 1.Slows down the movement of hydrogen ions thereby blocking the
effects of carbonic anhydrase resulting to more sodium and bicarbonate
Proximal Convulated Tubules loss
DIURETICS

61 62

CAI Diuretics CAI Diuretics

USES: ADVERSE EFFECTS:
Relatively mild diuretics GI Upset
DIURETICS

DIURETICS

Used in glaucoma Urinary infrequency 3.Metabolic Acidosis 4.Renal Calculi

Used in urinary alkalization Formation
Used in metabolic alkalosis 5.Prophylaxis for Acute Mountain Drowsiness and Paresthesia
Sickness 6.Adjuvants in the treatment of epilepsy Potassium wasting

63 64

VASODILATORS

65 66
 Direct Vasodilators
Vasodilators Oral Direct Vasodilators
Direct Vasodilators Hydralazine (Apresoline)

Vasodilators
Calcium Channel Blockers Minoxidil (Loniten)
Angiotensin Converting Enzyme
Inhibitors
Angiotensin II Receptor Blockers

67 68

Direct Vasodilators Mechanism of Action 1

Parenteral Direct Vasodilators u Increasing cGMP: cGMP facilitates the dephosphorylation of
myosin light chains, preventing the interaction of myosin with actin.
Vasodilators

Nitroprusside (Nitropress) Nitric oxide is an effective activator of soluble guanylyl cyclase and
acts mainly through this mechanism.
Diazoxide (Hyperstat IV)
Fenoldopam (Corlopam)

69 70

Mechanism of Action 2
u Decreasing intracellular Ca2+: Calcium channel blockers
predictably cause vasodilation because they reduce intracellular
Ca2+, a major modulator of the activation of myosin light chain
kinase.
71 72
 Mechanism of Action 3
u Stabilizing or preventing depolarization of the vascular
smooth muscle cell membrane: The membrane potential of
excitable cells is stabilized near the resting potential by increasing
potassium permeability. Potassium channel openers, such as
minoxidil sulfate, increase the permeability of K+ channels,
probably ATP-dependent K+ channels. Certain newer agents under
investigation for use in angina (eg, nicorandil) may act, in part, by
this
mechanism.

73 74

Mechanism of Action 4
u Increasing cAMP in vascular smooth muscle cells: An
increase in cAMP increases the rate of inactivation of myosin light
chain kinase, the enzyme responsible for triggering the interaction
of actin with myosin in these cells. This appears to be the
mechanism of vasodilation caused by b2 agonists, drugs that are
not used in angina.

75 76

Hydralazine Hydralazine
Oral Direct Vasodilators

Oral Direct Vasodilators

Absorption: well absorbed in the GIT USE

Metabolism: Acetylation 1. Used in chronic hypertension and in hypertensive crisis
T1/2: 2-4 hours accompanyingacute glomerular nephritis or eclampsia

77 78
Hydralazine Minoxidil
Oral Direct Vasodilators

Oral Direct Vasodilators

ADVERSE EFFECTS Description:
SLE-like syndrome Arteriolar vasodilator
Tachyphylaxis Oral treatment for sever to malignant hypertension
HA, N/V, Sweating, Arrhythmia, Angina, Palpitation,
Anorexia, Flushing

79 80

Minoxidil Minoxidil
Oral Direct Vasodilators

Oral Direct Vasodilators

Absorption: well absorbed in the GIT Metabolism: ADVERSE EFFECTS

Conjugation Distribution: Not protein bound T1/2: 2-4 HA, sweating, and hirsutism
hours Sodium and water retention, volume overload, edema

81 82

Nitroprusside Nitroprusside
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

Description: Description:
1. Complex of Iron, Cyanide and Nitroso moiety Aqueous solution sensitive to light
Mixed vasodilator
Powerful parenterally
83 84
Nitroprusside Nitroprusside
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

MOA
MOA
1. Dilatesbotharterialand venous vessels
Dilates
1. both arterial and
venous vessels

85 86

Nitroprusside
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

USES
Drug of Choice for all Hypertensive Emergencies and
Crises
Used in severe cardiac failure
Maintaincontrolled hypotension during surgery
Nitroprussid
e1. Accumulation of Cyanid
results to
Adverse Effects e
87 88
Metabolic
Acidosive
Excessi s
Arrhythmsion
Hypoten ia
Methemoglobinemia

Nitroprusside Diazoxide
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

Adverse Effects Description

1. Accumulation of Thiocyanate results to Weakness Chemically related to thiazide diuretic
Disorientation Psychosis Muscle Spasms Convulsions
It can cause fluid overload
Delayed Hypothyroidism
Longactingarteriolar vasodilator
Given with Beta blocker

89 90
Diazoxide Diazoxide
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

USES
IV fop HTN emergency
Hypertensive encephalopathy
Eclampsia

91 92

DIAZOXIDE FENOLDOPAM
Parenteral Direct Vasodilators

Parenteral Direct Vasodilators

Adverse Effects
Hypotension
Hyperglycemia
Renal and Salt Retention
Caution: Renal Impairment

93 94

FENOLDOPAM Calcium Channel Blockers

Parenteral Direct Vasodilators

1.Phenylalkylamines 2.Benzothiazepines 3.1,4-

dihydropyridines
Classes
95 96
Calcium Channel Blockers Description

Calcium Channel Blockers

It blocks the L-type calcium channel in heart and in blood
vessels
Prolongs depolarization
SA and AV node block

97 98

Non-Dihydropyridines
Calcium Channel Blockers

1. Vascular smooth muscles & cardiac muscles

o Vasidilation - ↓ TPR
o(-) inotropic / chronotropic effect -
↓ CO

99 100
Non-Dihydropyridines
Calcium Channel Blockers

Dihydropyridines:
o Amlodipine, Felodipine, Isradipine,
Nicardipine, Nifedipine, Nisoldipine
Block Ca + 2 channel in vascular smooth
muscles
Vasodilation - ↓ TPR
101 102
ACE Inhibitors ARBS
1. Captopril,Enalapril, Lidinopril, Benazepril, Fosinopril, Moexipril, uCandesartan cilexetil, Eprosartan, Irbesartan,
Perindopril, Quinapril, Ramipril,
Trandolapril
Losartan, Olmesartan, Telmisartan, Valsartan
↓ Angiotensin II →↓ Vasoconstriction →↓
TPR
↓ Angiotensin II →↓ Aldonesterone →↓
Ns, H2O retention →↓ BV →↓ CO
Classes

ARBS
103 104

Centrally-acting or Alpha 2 Agonist

Methyldopa
uDecrease sympathetic outflow from the brain
↓NE release uAgonist at presynaptic a2 receptors in the brainstem
Centrally-acting

Methyldopa uDue to stimulation od central a adrenoceptors by a -

Clonidine methyldopamine & a- methyINE
Guanabenz
guanfacine

105 106

Clonidine
Alpha-1 Blockers
uAgonist at alpha-2 receptors
Centrally-acting

uMild and moderate hypertension that has not

Prazosin, Terazosin, Doxazosin
responded adequately to treatment with a diuretic or
Primary hypertension
a β – blocker
Benign Prostatic Hyperplasia
uParticularly valuable in hypertension complicated by
renal disease.

107 108
 “First-Dose Phenomenon”

uSyncope in 1% with prazosin 2mg or above

uCommon in patients taking diuretics or beta-blocker
uBest started on a low dose and taken at hs

Β-Blockers
↓HR, contracility →↓ CO
Block stimulation of renin secretion
Primary hypertension
Bisoprolol, Carvedilol, Metoprolol

109 110

Nonselective Selective
Propranolol Betaxolol Mixed ¤- & β- blockers Intrinsic Sympathomimetic Activity (ISA)
Nadolol Bisoprolol
Labetalol Acebutolol
Timolol Esmolol
Carvedilol Pindolol
Pindolol Acebutolol
Sotalol Atenolol Penbutolol

βBlockers
Metoprolol
βBlocker
s

111 112

Peripheral-acting or Alpha 2 Agonist

uTrimethaphan
Membrane Stabilizing Activity Chronic open – angle glaucoma uReserpine
Pindolol Timolol
Propranolol Betaxolol uGuanethidine uGuanadrel
Acebutolol
Metoprolol

βBlockers
113 114