Prelim Reviewer Pcol

OLFU College of Pharmacy (Laguna Campus) Prelim Term
PCOL211 - PHARMACOLOGY 1 Second Semester

Professor: Ma’am Marijen Y. Soto S. Y. 2023-2024
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Week 2: Review of Pharmacodynamics
• Pharmacodynamics B. Target protein mediated mechanism

→ A branch of pharmacology that focuses on the study of
the biochemical and physiological effects of drugs and Target protein
the mechanisms by which they produce such effects. → biologic site of action of drugs
→ “what the drug does to the body” a. Structural Proteins

→ constitute “cytoskeleton” (cell framework)
Part 1:
Mechanisms of Drug Action Microtubule (and tubulins)
→ important site of action
A. Non – target protein mediated mechanism Drugs that inhibit microtubule synthesis/ spindle
protein
→ exert effects without binding to proteins.
• Griseofulvin → antifungal (targets fungal mitosis)
1. Colligative mechanism • Vinca alkaloids → antineoplastic/anticancer
• Colchicine → first line agent in the management of gout
→ osmotic effect
• Etoposide
→ Mass effect
b. Regulatory Proteins
* Osmosis → spontaneous passage or diffusion of water or
other solvents through a semipermeable membrane → mediates the transmission of endogenous
chemical signals such as neurotransmitters,
Eg. Mannitol autacoids, and hormones.
.
→ osmotic diuretic (IV) 2.1 Transports/Channels
→ SE: diarrhea (given orally) → Proteins that take part in transmembrane
signaling and regulates ionic composition
2. Chemical reaction
• NEUTRALIZATION
• Local
• Systemic
• CHELATION/COMPLEXATION
• DEFEROXAMINE → used for iron poisoning 2.2 Enzymes
→ protein catalysts (Inhibitors)
• OTHERS
• CN + Sodium thiosulfate Xanthine oxidase - allopurinol
3. Counterfeit incorporation mechanism
Cyclooxygenase - NSAID’s
ACE (angiotensin converting enzyme) ACE inhibitors
MAOI - Phenelzine
(Monoamine Oxidase) - Isocarbozaxid
- Tranylcypromine
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Acetylcholinesterase - Edrophonium GABA receptors control Cl- ions stimulated by:

COMT (catechol-O-methyltransferase) -Entacapone, Tolcapone -Benzodiazepines
-Barbiturates
2.3 Carrier Molecules
Nicotinic receptors
• control the entry of Na+
• inhibited by neuromuscular blocker
2. Type II Receptor
→ G-protein linked
receptor
2.4 Receptors • GTP-binding signal transducer protein is G-Protein

→ Functional macromolecular components of cells • G-protein modulates production of an intracellular
with specific stereochemical configuration and second messenger.
in which a ligand interacts
Examples of G-proteins:
• SPECIFICITY ● Gs-stimulates adenylyl cyclase
• SELECTIVITY ● Gi-inhibits adenylyl cyclase
● Gq-increases IP3 (inositol
Ligand triphosphate) DAG (diacylglycerol)
→ any chemical that has ability to bind
to a receptor cyclic adenosine monophosphate (cAMP)
cyclic guanosine monophosphate (cGMP)
Type of Receptors Inositol triphosphate (IP3)
1. Type I Receptor Examples of Type II receptors

→ (“ionotropic receptor”) 1. Adrenergic receptors (Adrenoceptors)
→ (“ligand-gated ion channels”)
● alpha receptors
→ a receptor protein that forms a part of a ligand-gated ion ● Beta receptors
channel, so that binding of ligand to the receptor causes
the opening of channel, permitting ions to flow through it. 2. Muscarinic receptors
- Controls movement of ions
- Found in cell membranes Type III Receptor
- Stimulated in milliseconds
*Tyrosine kinase → catalyze phosphorylation of tyrosine
residues to modulate a number of biochemical processes.
Examples:
Imatinib → gastrointestinal stromal tumors (GIST)

Gefitinib → epidermal growth factor receptor
Erythropoietin receptor
Receptor for Insulin → utilization of glucose
Platelet → derived growth factor
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4. Type IV Receptor - “gene transcription-linked receptors” Theories of Drug Receptor Interaction
location: nucleus/cytosol (cytoplasm) • Occupancy Theory

onset: hours
→ drug effect is directly proportional to
Central dogma the number of receptors occupied.
• replication (DNA copied into complimentary DNA)
• transcription (DNA template is copied to RNA) • Ariens and Stephenson Theory
• translation (RNA synthesize protein) → occupational theory of response.
Drugs that act on Type IV receptors • Rate Theory

• Corticosteroids → the activation of receptors is directly
• Mineralocorticoids proportional to the total number of
• Sex steroids encounters of the drug with its receptors per
• Vitamin D unit time.
• Thyroid hormone
• Retinoids Pharmacodynamics
Receptor Interactions Types of Receptor Action
2. Lock and Key Theory 1. Down Regulation

→ the drug molecule must “ fit into a receptor” like a “key
fits into a lock”. → is caused by continuous prolonged exposure
of receptors to drugs that disrupt the
homeostatic equilibrium; due to altered levels
of receptors.
2. Desensitization
→ result of down-regulation; effect of

subsequent exposure of the receptors to the
same concentration of the drug is reduced.
3. Induced-Fit Theory 3. Sensitization or Up-regulation

→ as the drug approaches the receptor, it alters the 1. Prolonged/continuous use of receptor blocker
conformation of its binding site to produce a drug-receptor 2. Inhibition of synthesis or release of
complex. hormone/neurotransmitter - Denervation
4. Hyperactivity/Supersensitivity
→ occurs when target cells are subject to long
term exposure to receptor antagonists followed
by abrupt cessation of administration of the
drug.
→ up-regulation through synthesis of
new receptors.
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Part 2:
Dose- Response Relationship A. POTENCY
Drugs A and B are said to be more potent than drugs C
• a.k.a. “ Exposure-Response Relationship” and D because of the relative positions of their dose
→ describes the change in effect on organism caused by response curves along the dose axis.
differing levels of exposure (dose) to a stressor (chemical)
after a certain exposure time. B. Maximal Efficacy
This parameter reflects the limit of the dose-response
• Graded Dose-Response Curve relation on the response axis. Drugs A, C,and D have
➔It is a graph of response versus the logarithm of the equal maximal efficacy, while all have greater maximal
dose yields the efficacy (Emax) and potency (ED50). efficacy than drug B.
➔ It is the magnitude or the intensity of the C. Shape of Dose-Response Curves

pharmacological response that increases as the dose reflects the ability of the drug to produce an effect. The
administered increases. STEEPER the slope, the more readily the drug will bind
with receptors.
It allows comparison for drug efficacies and potencies.
Extremely steep dose-response curves
Efficacy
→ refers to the ability of the drug to elicit a response (eg, curve D) may have important clinical consequences
at the molecular, cellular, tissue or system level. if the upper portion of the curve represents an
undesirable extent of response (eg, coma caused by
→ It is measured by its maximum effect. a sedative-hypnotic)
→ a. k. a. “Intrinsic Activity” Steep dose-response curves in patients could result

from cooperative interactions of several different actions
Potency of a drug
→ refers to the concentration(EC50) or dose (ED50)
of a drug required to produce 50% of the drug's (eg, effects on brain, heart, and peripheral vessels, all
maximal effect contributing to lowering of blood pressure)
→ is a measure of drug activity expressed in terms • Quantal Dose-Response Curve

of the amount required to produce an effect of given ➔ All-or-none response
intensity. ➔ It is a graph of the number of patients that
responds by a specified dose.
Ceiling Dose ➔ The magnitude of drug effect is selected and the
→ is the maximum amount of drug that can induce number of individuals within population of response is
biological effect by a given drug. quantified as the dose is increased.
Quantal dose-effect curves

→ may also be used to generate information regarding
the margin of safety to be expected from a
particular drug used to produce a specified effect.
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Therapeutic Index Hypersensitivity Reactions
→ is a comparison of the amount of a therapeutic
agent that causes drug toxicity.
Type Other Names Examples Mediato
r
→ the dose of a drug required
to produce a desired effect to I Allergy •Atopy IgE
(Immediate) •Anaphylaxis
that which produces an •Asthma
undesired effect
→ a.k.a. “Therapeutic Ratio”.
II Cytotoxic, •Autoimmune IgM or
• Median toxic dose (TD50) Antibody Hemolytic IgG
dependent Anemia
→ the dose required to produce a particular toxic effect •Thrombocytopenia
in 50% of animals. •Erythroblastosis
fetalis
• Median Lethal Dose (LD50)
III Immune •Serum sickness IgG
→ the dose that can produce death in 50% of the Complex •Systemic Lupus
animals. Disease Erythematosus
(SLE)
IV Delayed-Type •Contact Dermatitis T-cells

Hypersensitivity •Mantoux Test
•ChronicTransplant
Rejection
•Multiple Sclerosis
V Autoimmune •Grave‟sDisease IgM or

Disease •Myasthenia Gravis IgG
• Tolerance
Variation in Drug Responsiveness → it refers to a decreased responsiveness to the drug,
a consequence of continued drug administration.
• Idiosyncracy
→ Unusual drug Response caused by genetic • Tachyphylaxis
differences in metabolism of the drug or by → This refers to rapidly acting tolerance
immunologic mechanisms, including allergic reactions.
→ Responsiveness diminishes rapidly after
• Hyporeactivity administration of a drug.
→ the intensity of effect of a given dose of drug is
diminished. Factors Influencing Drug Effects
1.WEIGHT → adipose tissue > toxic
• Hyperreactivity Effects
→ the intensity of effect of a given dose of drug is
increased in comparison to the effect seen in most 2. AGE
individuals. Infants → underdeveloped liver enzyme
system = (inc) toxic effect
• hypersensitivity Chloramphenicol
→ refers to allergic or other immunologic responses to → gray baby syndrome
drugs. Geriatric patients
→ deteriorating body functions
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3. Gender → for IM injection
Male>Female in terms of vascular muscles. 1. PHARMACOLOGIC ANTAGONIST
→ inhibits the activity of an agonist by reacting with the
→ Effects faster in male than female receptor or other part of the effectors mechanism.
4. PATHOLOGICAL FACTORS 1.1 PHARMACODYNAMIC ANTAGONIST

liver disease = (dec) biotransformation of drugs → produce an effect opposite of agonist by
= (inc) toxic effects binding to the same receptor
→ Beta blocker and Beta agonist
5.GENETIC FACTORS (Propranolol) (epinephrine)
ASIANS are fast acetylators
Acetylation (metabolizing INH) = (dec) antitubercular effects
Part 3:
Concepts of Agonism, Antagonism, Allosteric Modulation
Classification of drugs according to receptor interaction
1.2 PHARMACOKINETIC ANTAGONIST

→ Reduce the effect of one drug by
alteration of ADME
→ Eg. Digoxin + Cholestyramine
2. PHYSIOLOGIC ANTAGONIST
→ occurs when the drugs act independently at different
receptor sites, often yielding opposing actions.
e.g. HISTAMINE + EPINEPHRINE

Histamine + Salbutamol
Glucocorticoid + Insulin
Types of Agonist
1. Full Agonist 3. CHEMICAL ANTAGONIST

→ Full response → no receptor is involved
→ Stimulate all different variant of receptors even the new → occurs when two drugs bind with each other to form an
receptors. inactive compound.
2. Partial Agonist
→ partial agonists competitively inhibit the responses Examples:
produced by full agonists. Paracetamol + N-Acetylcysteine
3. Inverse Agonist Warfarin + Vitamin K
→ drug that binds to the agonist same binding for that Examples
receptor constitutive activity site as an
Protamine SO4 + Heparin SO4 → forms
and reverses of receptors.
a complex devoid of action
Protamine- (+) charged at physiologic pH

Types of Antagonism Heparin – (-) charged at physiologic pH
1. Pharmacologic Antagonism Chelating agents

2. Physiologic Antagonism Deferoxamine – Iron (Fe)
3. Chemical Antagonism
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• Nature of Antagonism
→ It depends on whether or not they reversibly compete Pharmacologic Profile Tests
with agonists for binding to receptors
Experimental Method or Target
• COMPETITIVE ANTAGONISM Organ: Systems- Blood pressure
→ Effects of Antagonist can be
overcome/reversed by increasing the Species or Tissue: Dog, cat (anesthetized)
concentration of agonist
Route of Administration: Parenteral
• NON-COMPETITIVE ANTAGONISM Measurement: Systolic-diastolic
→ it is also known as irreversible antagonism changes
Example: Phenoxybenzamine Experimental Method or Target Organ: Respiratory effects

DNA-alkylating agents
Species or Tissue: Dog, guinea pig
• Allosteric Modulation Route of Administration: Parenteral
→ is the regulation of an enzyme or other protein by binding Measurement: Effects on respiratory
an effector molecule at the protein‟s allosteric site. rate and amplitude, bronchial tone
Types of Allosteric Modulation Goals of preclinical studies
1. Positive Allosteric Modulation • identifying all potential human toxicities;

→ occurs when the binding of one ligand enhances the
attraction between substrate molecules and other binding • designing tests to further define the toxic mechanisms;
sites.
→ a.k.a. “allosteric activation”. • and predicting the specific and the most relevant toxicities
to be monitored in clinical trials
Example:
Hemoglobin + Oxygen Quantitative estimates are determined
2. Negative Allosteric Modulation 1. "no-effect" dose → the maximum dose at which a

→ occurs when the binding of one ligand decreases specified toxic effect is not seen
the affinity for substrate at other active sites.
→ a.k.a. “allosteric inhibition”. 2. the minimum lethal dose → the smallest dose that is
Example: observed to kill any animal
Glycine + Strychnine (spinal convulsant)
Note: Strychnine blocks Glycine receptor 3. the median lethal dose (LD50) → the dose that kills
which is numerous in the spinal cord approximately 50% of the animals.
convulsion.
Part 4 :
Basic & Clinical Evaluation of New Drugs
Drug Screening
→ it involves a sequence of experimentation and
characterization of drugs.
Determination of the ff.

1. pharmacologic profile of the drug
Effects on cell function
pharmacologic activity and selectivity of the new compound
in comparison with reference compounds.
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Week 3: AUTACOIDS- HISTAMINE
PART 1
Autacoids - Histamine Distribution of Histamine
• AUTACOIDS • Histamine
→ a.k.a. “Local hormones” → is found in many tissues, including the brain.
→ endogenous substances with biological activity.
→ not released or stored in glands. → it is stored and found in the highest amounts in
→ not circulated in blood. mast cells and basophils.
→ are formed at the site of action.
→ produce localized action.
Two processes by which HISTAMINE IS RELEASED
Classification of Autacoids
1. Energy- and Ca2+
→ dependent degranulation reaction.
1. Biologically active amines
● Histamine 2. Energy- and Ca2+
● Serotonin → independent release (displacement).
2. Lipid derived autacoids ( Eicosanoids)

● Prostaglandins Chemical & Mechanical Release
● Leukotrienes
● Thromboxanes • Occurs following chemical or mechanical injury to mast
cells.
3. Ergot Alkaloids
• Displacement is induced by drugs such morphine,
4. Vasoactive polypeptides tubocurarine, guanethidine, and amine antibiotics.

• does not require energy.
● Vasopressin
● Angiotensin
Types of Histamine Receptors
● Kinins
● Endothelin
● Natriuretic peptide Receptor Distributio Post Partial Partial
Type n Receptor Agonists Antagonist
● substance P Mechani s
sm
5. Endothelium derived autacoids
H1 Smooth IP3, DAG 2-(mFluoro Mepyramine
● Nitric oxide muscle, (Gq) phenyl)- ,
endotheliu histamine Triprolidine
m
brain
H2 Gastric cAMP Dimaprit, Ranitidine,

mucosa, (Gs) Impromidin Tiotidine
cardiac e,
muscle, Amthamine
mast cells,
brain
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H3 Presynaptic cAMP, R-a-Methyl Thioperamid
Adverse effects of HISTAMINE AGONISTS
: Ca2+ Histamine, e, ■ Flushing
brain, (Gi) Imetit, Iodophenpro ■ Hypotension
myenteric Immepip pit,
plexus Clobenpropit ■ Tachycardia
■ Headache
H4 Eosinophils cAMP, Clobenpropi Thioperamid
,neutrophils Ca2+ t, e
■ Wheals
, CD4 (Gi) Imetit, ■ Bronchoconstriction
T-cells Clozapine ■ Gastrointestinal upset
A. Histamine (H1)-receptor antagonists
• Aka: “classical ANTIHISTAMINES”

• competitive inhibitors at the H1-receptor.
CLASSES of Histamine (H1)-receptor antagonists
1. 1st Generation Antihistamines
HISTAMINE AGONISTS a. Ethanolamines: (antiemetics)

■ Histamine Carbonoxamine, Dimenhydrinate,
→ R-alpha methylhistamine is an H3-specific Diphenhydramine, Doxylamine (sleeping aid)
agonist.
b. Ethylaminediamines:
■ Betazole (histalog)
→ tenfold greater activity at H2-receptors than at Pyrilamine, Antazoline, Tripelennamine
H1-receptors → produce moderate sedation
→ can cause gastrointestinal upset
■ Impromidine
→ investigational agent; its ratio of H2:H1 activity c. Piperazine: (Antiemetics, anti-motion sickness)
Hydroxyzine, Cyclizine, Meclizine
is about 10,000
d. Alkylamines:
Brompheniramine, Chlorpheniramine
USES OF HISTAMINE AGONISTS → Agents which produce slight sedation
o used in allergy testing to assess
histamine sensitivity e. Phenothiazines:
Promethazine (antiemetic)
o in the test of gastric secretory function → weak alpha-adrenoceptor antagonist.
Function: they have been largely supplanted for this use f. Miscellaneous:
by pentagastrin. Cyproheptadine antihistamine, anticholinergic,and antiserotonin
activities.
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2. 2nd Generation Antihistamines (marked by sedation, decreased alertness, and
a. Piperidines: decreased appetite)
Fexofenadine (Allegra) - safer antihistamine
Astemizole (Hismanal) • In children and some adults, these agents
Terfenadine (Seldane) stimulate the CNS.
b. Miscellaneous:
Loratidine, Cetirizine (Zyrtec)
Therapeutic Uses
✓Poor CNS penetration, less sedating
H1-receptor antagonists
Pharmacokinetic Properties of H1 Blocking Drugs
• Treatment of allergic rhinitis and
A. well absorbed after oral administration. o Normal
conjunctivitis.
effects seen in 30 minutes (with maximal effects at
1-2 hours)
✓ treat the common cold based on their
anticholinergic properties
o The duration of action is :
❑ 1ST generation compounds: 3-6 hours
✓ Diphenydramine also has an antitussive
❑ 2ND generation compounds: 3-24 hours
effect not mediated by H1→ receptor
antagonism.
B. lipid-soluble → cross the blood-brain
barrier • Treatment of urticaria and atopic dermatitis,
including hives
C. metabolized in the liver
→ many induce microsomal enzymes • Sedatives
and alter their own metabolism
✓Several (doxylamine, diphenhydramine)
Pharmacologic Actions: are marketed as over-the-counter (OTC)
sleep aids.
• ethanolamine, phenothiazines, and
ethylenediamines • Prevention of motion sickness
→ have ANTICHOLINERGIC activity. • Appetite suppressants
• block mucus secretion and sensory nerve Adverse Effects

stimulation. (significantly reduced with second-generation agents)
• effective local anesthetics • sedation (synergistic w/ alcohol, other

→ Eg. Dimenhydrinate and promethazine depressants, dizziness, and loss of appetite.
• relax histamine-induced contraction of bronchial • gastrointestinal upset, nausea, constipation

smooth muscle and have some use in allergic and diarrhea.
bronchospasm.
• anticholinergic effects (dry mouth, blurred
• block the vasodilator action of histamine. vision, and urine retention).
• inhibit histamine-induced increases in capillary
permeability. H2-receptor Antagonists
• frequently cause CNS depression (1) Histamine (H2) → receptor antagonists
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include
✓ Cimetidine (Tagamet) PART 2
✓ Ranitidine (Zantac) Agents used in Peptic Ulcer Disease
✓ Famotidine (Pepcid AC)
✓ Nizatidine (Axid) • Peptic Ulcer
(2) competitive antagonists at the H2- receptor, → A circumscribed loss of the mucous membrane of
which predominates in the gastric parietal cell. the GIT system exposed to gastric juices containing
acid and pepsin.
USE/S:
◼ treatment of gastrointestinal disorders: → Characterized by gnawing, burning or aching pain
(worsen at night), N/V, belching and weight loss
✓ heartburn and acid → induced indigestion
✓promote the healing of gastric and duodenal • Excessive secretion of gastric acid
ulcers – Gastric Ulcer (Stomach)
✓ hypersecretory states such as Zollinger Ellison – Duodenal Ulcer (Duodenum)
syndrome – Esophageal Ulcer (Esophagus)
Inhibitors of histamine release: Duodenal Ulcers vs Gastric Ulcers

- other term for mast cell stabilizers
• Duodenal Ulcers
✓cromolyn (Intal) → Age 25-75 yrs
✓nedocromil sodium (Tilade) → Gnawing or burning upper abdomen pain
relieved by food but reappears 1-3 hrs after
meals.
1. poorly absorbed salts;
→ Worse pain when stomach is empty
ROUTE of admin: inhalation
→ Bleeding occurs with deep erosion
2. They inhibit the release of histamine and other

❖ Hematemesis
autacoids from the mast cell. ***increase influx of
❖ Melena
Chloride ions
• Gastric Ulcers
3. Prophylactic agents in asthma. – Age 55-65 yrs
– Relieved by food but pain may persist even after
4. Nedocromil sodium eating
→ appears to be more effective in reducing – Anorexia, wt loss, vomiting
bronchospasm caused by exercise or cold air. – Infrequent or absent remissions
– Small % become cancerous
5. adverse effects: sore throat and dry mouth. – Severe ulcers may erode through stomach wall
*Additional notes
What may continue imbalance?
1st Gen 2nd Gen
sedation No sedation • Helicobacter pylori

• NSAID’s
Greather Lipid soluble Less lipid • Ethanol
• Tobacco
increase ADR decrease ADR • Severe physiologic stress (Burns, CNS trauma, surgery)
*EIB- Exercise Induced Bronchospams • Steriods
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Goal Therapy
H. pylori
1. Reduce Gastric acid production
- H2 antihistamines, PPIs, Anticholinergics, PG
• Gram (-) rod with flagella . analogs
• H pylori is most common cause of 2. Neutralize gastric pH
PUD - Antacids
• Transmission route fecal-oral 3. Protect the walls of the stomach from the acid and
• Secretes urease → convert urea to ammonia pepsin released by the stomach
• Produces alkaline environment enabling survival in - Ulcer protectives
stomach. 4. Treat peptic ulcer and reflux esophagitis
• Almost all duodenal and 2/3 gastric ulcer pt's
infected with HP Classification
• Considered class 1 carcinogen → gastric cancer 1. Acid Neutralizing agents: (ANTACIDS)
• Systemic: Sodium Bicarbonate and Sod. Citrate
• Nonsystemic: Magnesium hydroxide, Mag.
Differentiating between H. Pylori and NSAID-induced ulcer Treisilicate, Aluminium hydroxide gel, Magaldrate and
calcium carbonate.
• Ulcers associated with H. Pylori
– More often in duodenum 2. Reduction in Gastric acid secretion:
– Often superficial • H2 antihistamines: Cimetidine, Ranitidine,
– Less severe GI bleeding Famotidine, Nizatidine and Roxatidine
• Ulcers associated with NSAIDs (Mefenamic acid, aspirin) • Proton pump inhibitors: Lansoprazole Omeprazole,
– More often in stomach Pantoprazole, Rabeprazole and Esomeprazole (Lopre)
– Often deep
– More severe GI bleeding • Anticholinergics: Pirenzepine, Propantheline and
– Sometimes asymptomatic Oxyphenonium (Pop)
Complications of PUD • Prostaglandin analogue: Misoprostol

1. Bleeding
- occurs in 25-33%of patients
- most frequent complication and maybe life-threatening - 3. Ulcer protectives: Sucralfate, Colloidal Bismuth
account for 25% of ulcer deaths subcitrate
- may be the first indication of an ulcer
4. Anti-H. pylori Drugs: Amoxicillin, Clarithromycin,
2. Perforation metronidazole, tinidazole and tetracycline
– occurs in about 5% of the patients
- accounts for 2/3 of ulcer deaths H2 receptor antagonists (“tidine”)
3. Obstruction from edema or scarring A. Cimetidine (Tagamet®) (bumababa pag mayroong antacid)
– often due to pyloric channel ulcers ■ reduces acid secretion by 70% for 4-5
- occur with duodenal ulcer hours (300mg qid)
- causes incapacitating, crampy abdominal pain ■ bioavailability is reduced by antacids
- may lead to total obstruction with intractable vomiting ■ decreases the absorption of ketoconazole
4. Intractable pain
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major adverse effects include : gastritis
■ thrombocytopenia - prevent aspiration pneumonia
■ gynecomastia (spironolactone) and impotence - Hypersecretory states
(androgen receptor antagonist)
■ mental confusion in the elderly
■ low incidence of mild gastrointestinal A. Inhibitors of Gastric Acid Production
upset, headache 2. Proton pump inhibitors (PPI’s) “prazole”
■ Potent inhibitor of CYP450
■ IV : dementation and bradycardia (elderly) *LOPRE - Lansoprazole, Omeprazole
Rabeprazole Pantoprazole, Esomeprazole
B. Ranitidine (Zantac ®)
■ 5-10x more potent than cimetidine 2. Proton pump inhibitors (PPI’s)
- does not bind to androgen receptor
USES:
- secreted in milk therefore it should not be given in
- GERD
lactating mothers
- low incidence of headache and cutaneous rash - Duodenal and gastric ulcer. H.pylori ulcer,
- hepatotoxic NSAID-induced ulcer
C. Famotidine (H2-bloc ®) - Prevention of rebleeding from peptic ulcer
■ Most potent H2 blocker - non-ulcer dyspepsia
-approximately twice as potent as ranitidine - Prevention of stress-related mucosal bleeding
- tachyphylaxis compromise its long term use - Gastrinoma and Hypersecretory states
- has a longer duration of action
- produces fewer side effects similar to those • Lansoprazole
of ranitidine - acid labile and administered as an enteric coated tablet
- mild cardiotoxic - prodrug that requires protonation for activation
- most effective when given 30 to 60 mins before meals
- its acid inhibitory effects is greater than 24 hours
D. Nizatidine (Accid ®)
- adverse effects include abdominal pain, nausea
– as effective as ranitidine and may be administered and diarrhea
once daily - it can increase theophylline clearance
- may produce hepatotoxicity but it does not inhibit drug - it is contraindicated in asthma
metabolism in the absence of liver damage
- does not bind to androgen receptors
• Omeprazole
-given as delayed release capsule due of acid lability
*CRFN - Cimetidine, Ranitidine, Famotidine, Nizatidine
-antisecretory effects occurs within 1 hour with the maximum
effects occurring within 2 hours
Mechanism of action: -it may produce abdominal pain, nausea, diarrhea, vomiting,
rash, constipation, headache, asthenia and back pain
→ decrease gastric acid secretion through competitive -may inhibit the metabolism of warfarin, diazepam, and
inhibition of H 2 receptors. phenytoin
-it inhibits the absorption of ketoconazole
-contraindicated in pregnancy.
A. Inhibitors of Gastric Acid Production
PPI - Dosage Schedule
1. H2 receptor antagonists
USES:
- GERD Generic Name Brand Name mg o.d.
- Duodenal and gastric ulcer
Lansoprazole Omepron 30mg o.d.
- non-ulcer dyspepsia
- prophylaxis for recurrent ulcers in patients Omeprazole Prevacid 20mg o.d.
- control of reflux esophagitis and bile reflux
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occuring prostaglandin
Pantoprazole Pariet 40mg o.d.
– Inhibits gastric acid secretion and increases mucosal
Rabeprazole Pantoloc 20mg o.d. resistance
– FOR NSAID INDUCED ULCER
Esomeprazole Nexium 20 - 40mg o.d.
4. Cytoprotective agents
MOA → increases mucus and bicarbonate secretion by the
3. Anticholinergics
gastric epithelium by increasing epithelial regeneration and
by enhancing mucosal blood flow, thus enhancing mucosal
• Includes propantheline, isopropamide and
protection.
scopolamine
• Decrease ACh-stimulated secretion and motility in the
Colloidal Bismuth Compounds
GIT
■ bismuth subsalicylate
• Required doses produce systemic anticholinergic fx
■ bismuth subcitrate
• They are rarely used alone but they are useful as
■ bismuth dinitrate
adjuncts in patients resistant to H2 blockers
MOA:
■ coats ulcers and erosions, creating a protective layer
against acid and pepsin.
B. Cytoprotective agents ■ It may also stimulate prostaglandin, mucus, and
bicarbonate secretion
• Sucralfate (Iselpin®) (aluminum sucrose sulfate) Bismuth

■ has direct antimicrobial effects and binds enterotoxins,
→ A complex polysaccharide complexed with aluminum accounting for its benefit in preventing and treating traveler's
hydroxide diarrhea.
→ Has affinity for exposed proteins in the crater of
peptic ulcer (coats the ulcer bed) ■ direct antimicrobial activity against H pylori.
→ Protects ulcerated areas from further damage and
promotes healing Clinical Uses
■ nonspecific treatment of dyspepsia and acute diarrhea
MOA: stimulates mucosal production of PG and inh ■ prevention of traveler's diarrhea (30 mL or 2 tablets four
pepsin. times daily)
■ for the eradication of H pylori infection.
- it may produce constipation and nausea, gastric discomfort,
indigestion, dry mouth, rash, pruritus, back pain, dizziness, Adverse Effects
sleepiness and vertigo, hypophosphatemia ■ causes blackening of the stool
■ Liquid formulations may cause harmless darkening of the
Sucralfate tongue.
• Taken on empty stomach 1 hr. before meals ■ Bismuth agents should be used for only
• Concurrent antacids, H2 antagonist avoided (as it needs short periods and should be avoided in patients with renal
acid for activation) insufficiency.
• Uses: ■ bismuth toxicity resulting in encephalopathy
(ataxia, headaches, confusion, seizures).
- NSAID induced ulcers
- Patients with continued smoking
CARBENOXOLONE
- ICU
■ synthetic derivative of glycyrrhizic acid
- Topically-burn, bedsore ulcers, excoriated skins
■ heals both gastric and duodenal ulcers
• Dose: 1 gm 1 Hr before meals
MOA: increases production, secretion and viscosity of
• Misoprostol (Cytotec®) intestinal mucus
– A PGE1 analog A/E: Aldosterone effect
– More water soluble and it has a t1/2 than naturally
Carisma II 14
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• Can cause electrolyte disturbance and alkalosis
Antacids
ANC= Antacid Neutralized Capacity ■ Non- systemic antacids: Al, Ca, Mg
• Form insol compounds in the GIT
■ Types of antacids
➢ Systemic antacids The patient
➢ Sodium bicarbonate ■ Patients with increase risk of antacid
➢ Calcium carbonate toxicity
• Heart failure = excess sodium intake (inc. toxicity)
■ Nonsystemic antacids
• Renal failure = should not use magnesium containing
➢ Aluminum hydroxide (Amphojel)
antacids ( can cause hypermagnesemia) or sodium
➢ Dihyroxyalumium sodium (Rolaids)
bicarbonate (systemic alkalosis)
➢ Calcium carbonate (Tums)
= given with aluminum containing antacids for
➢ Magaldrate (Riopan)
their phosphate lowering effect.
➢ Magnesium hydroxide and aluminum hydroxide
(Maalox, Mylanta, Gelusil)
Differences in the types of Antacids C. Antacids

■ Cation content ■ Sodium bicarbonate
■ Neutralizing capacity → absorbed systemically and should not be used for
■ Duration of action long-term treatment contraindicated to hypertension due
■ Side effects to its high sodium content.
■ Cost → Potent neutralize capacity and acts instantly
Neutralizing capacity NOT USED ANYMORE FOR ITS DEMERITS

■ ANC = number of mEq of HCl required to maintain
1 mL of an antacid suspension at pH 3 for 2 hr in → Sustemic alkaloids
vitro. → Distension,discomfort and belching - Co2
■ Factors that can cause variation in the rate of → Rebound acidity
neutralization → Sodium overload
➢ Degree of comminution
➢ Crystal form
■ Calcium carbonate
➢ Precipitants used
→ partially absorbed from the gastrointestinal tract and
➢ Presence of reactive suspending agents
have some systemic effects should not be used for long
term use may stimulate gastrin release and thereby
Dosing interval
cause rebound acid production contraindicated in renal
• Ideal antacid should be rapid in onset and provide a disease.
continuous buffering action
• Rapid onset: Mg(OH)2, MgO, CaCO 3 • ADR:
• Slow onset: Mg trisilicate and aluminum compounds Hypercalcemia, Alkalosis Renal failure (milk-alkali
syndrome)
Duration of buffering action
• determined by the administration of antacid ■ Magnesium hydroxide
• With food: action will last for 2 hr not absorbed in the GIT therefore produces no systemic
• An additional 3 hr meals will extend the buffering time by 1 effects can be used for long term therapy
hr may produce diarrhea
• Ideal dosing interval: 1 and 3 hr after meals and at bedtime
• Magnesium containing preparation
Side effects Diarrhea
■ Systemic antacid: Sodium bicarbonate Hypermagnesemia
• Soluble and readily absorbed
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■ Aluminum hydroxide ■ 2. It reduces intestinal fluid secretion and pancreatic
→ has no systemic effects and causes constipation secretion.
→ Also hypophosphatemia and osteomalacia
■ 3. It slows gastrointestinal motility and inhibits gallbladder
contraction.
• Prolonged Aluminum use
Phosphate depletion, Osteoporosis, osteomalacia,
■ 4. It induces direct contraction of vascular smooth muscle,
neurotoxicity
leading to a reduction of portal and splanchnic blood flow.
■ Combination products ■ 5. It inhibits secretion of some anterior pituitary hormones.

→ various preparations that combine magnesium Octreotide
hydroxide and aluminum hydroxide • is a synthetic octapeptide with actions similar to
■ to achieve a balance between agents adverse somatostatin.
effects on the bowel. • When administered intravenously, it has a serum half-life of
1.5 hours.
• Examples of which are Maalox, Mylanta and • It also may be administered by subcutaneous injection,
Gelusil. resulting in a 6- to 12-hour duration of action.
• A longer-acting formulation is available for
Combination products once-monthly depot intramuscular injection.
1. Combine fast and slow reacting antacids to

obtain a product with a rapid onset and
relative even, sustained action.
2. Lower the dose of each component and

minimize the possibility of certain ADR
3. Use one component to antagonize one or

more side effects of another component.
Simethicone
■ Not an antacid
■ Used to defoam gastric juice to decrease
the incidence of gastroesophageal refluxCombination
products
Somatostatin
• is a 14 amino acid peptide that is released in the
gastrointestinal tract and pancreas from paracrine cells,
D-cells, and enteric nerves as well as from the Nonpharmacologic Measures
hypothalamus.
• Avoid tobacco
• short half-life in the circulation (3 minutes) when it is • Avoid alcohol
administered by intravenous injection. • Weight loss
• Avoid hot, spicy, and greasy foods
It is a key regulatory peptide that has myriad
physiologic effects:
• Take any NSAIDs including aspirin and oral
■ 1. It inhibits the secretion of numerous hormones, glucocorticoids with food or in deceased dosage
including gastrin, cholecystokinin, glucagon, growth • Sit upright
hormone, insulin, secretin, pancreatic polypeptide, • Do not eat before bed
vasoactive intestinal peptide, and 5- HT3. • Wear loose-fitting clothing
Carisma II 16
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Week 4(A): Pharmacology of Serotonin

• Perception of pain
Serotonin • Regulation of blood pressure
(5-Hydroxytryptamine) • Vomiting
Melatonin (Sedation)
• An important neurotransmitter
→ Regulates mood, sleep, appetite, and temperature N-acetyl-5-methoxytryptamine
regulation, as well as the methoxylated and N-acetylated
perception of pain, the regulation of blood pressure, and product of serotonin found in
vomiting the pineal gland.
Regulate sleep-wake behavior
of human
• A local hormone (Autacoid) in the gut
• It is a component of the platelet clotting process Platelets component of the platelet
clotting process.
Tryptophan → amino acid precursor of Serotonin
also known as thrombocyte
for them undergo blood clot.
Small intestine • Approximately 90% of

serotonin is found in the
(Enterochromaffin enterochromaffin cells of the
cells) gastrointestinal tract.
• Increases GIT motility
.Carcinoid tumor- excess of serotonin level Additional Notes:

Low 5-HT- depression, anxiety
High 5-HT- psychosis
Excess high- carcinoid tumor
Receptors of Serotonin
Serotonin
(5-Hydroxytryptamine)
DISTRIBUTION Pharmacological effects
Brain • Regulates mood, sleep, Most of serotonin receptors are Type II (G-protein linked)
(Neurotransmitter) appetite (low levels result to except 5HT3 are coupled to a Na+-K+ ion channel, Type I
anxiety, depression and sleep
(Ionotropic receptor)
trouble)
• temperature regulation
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Serotonin Agonists Tegaserod ⏤ 5HT4 partial Withdrawn due

agonist to
cardiovascular
Serotonin Details Brands ⏤ used for toxicity.
Agonists irritable bowel
syndrome with
Buspirone - ⏤ is a relatively constipation.
generic specific 5HT1a receptor
(Buspar) - agonist. Ergot alkaloids ⏤5HT1D
branded (Claviceps
⏤ Is useful for the purpurea) ⏤ERGOTAMINE:
management of anxiety Used for
Sedative disorders. prevention and
drugs/induce treatment of
calmness (panic attack) migraine.
⏤ERGONOVINE
Dexfenflurami ⏤ 5HT2c - Used in the
ne (increases serotonin) management
agonist of post-partum
⏤ Used as appetite hemmorhage
suppressant
⏤ Withdrawn: Ergot
cardiac valve toxicity
Triptans ⏤ a 5HT Serotonin Details

• Sumatriptan 1B/1D-receptor agonist. Agonists
(Imitrex,
Imigran) ⏤ promotes the contraction → Powerful hallucinogen
of vessels in → behavioral effects are mediated by
• Naratriptan
carotid circulation. agonist effects at prejunctional or
• Zolmitriptan This reduces the rebound postjunctional 5-HT2 receptors in the
(migraine) vasodilation associated central nervous system
Dilated with migraine headaches.
constrict
• Rizatriptan ⏤ used for the treatment of -→ affect the following receptors:
acute migraine. ● Adrenoceptors
Bawal sa ● dopamine receptors
⏤ A/E: ● 5-HT receptors
highblood dahil Hypertension
it will cause Ergotism → accidental ingestion of ergot
increases migraine- vasodilated in brain alkaloids in contaminated grain
Vasoconstricted- inc blood
Effect:
pressure
Vascular smooth muscle = Contraction
Cisapride ⏤ 5HT4 agonist
Uterus = contraction
(Propulsid)
Endocrine = suppress prolactin secretion from
⏤ speeds gastric pituitary cells
increase emptying and increases
movement lower esophageal
intestine pressure.
clinical Uses:
1. For Migraine
→ (Ergotamine, Cafeine)
⏤ Use: Treat nocturnal
heartburn due to reflux,
Methysergide → Its therapeutic effect in
constipation, and anorexia
migraine prophylaxis has been associated
nervosa.
with its antagonism at the 5-HT2B receptor
(PARTIAL AGONIST)
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→ It has a known side effect, retroperitoneal

fibrosis, which is severe although
uncommon.
• For Postpartum hemorrhage
-Ergonovine maleate
• Hyperprolactinemia
-Bromocriptine- trade names Parlodel,
Cycloset), an ergoline derivative
- Pergolide
1. OXYTOCIC
Selective serotonin reuptake inhibitors (SSRI) Serotonin Agonists

The most common antidepressant in clinical use.
MOA: Serotonin Details Brands
Inhibition of the serotonin transporter (SERT) Antagonists
Examples:
Trazodone ⏤ 5HT2 antagonists
(Desyrel) (peripheral)
1. Fluoxetine (Prozac) Nefazodone ⏤ Serotonin antagonist
2. Sertraline (Zoloft) (Serzone) and reuptake inhibitor
3. Citalopram (Celexa) (SARI) (central)
4. Paroxetine (Paxil)
⏤ Use: Antidepressant
5. Fluvoxamine (Luvox, Faverin)
6. Escitalopram (Lexapro) A/E: Priapism,
7. Dexfenfluramine (Redux) Hepatotoxicty
NOTES:
Cyproheptadine ⏤ a potent H1-receptor
Fluoxetine à norfluoxetine (Periactin) antagonist of the
Fluoxetine and paroxetine are potent inhibitors of phenothiazine class; it
CYP2D6 blocks
both 5HT1- and 5HT2-
Fluvoxamine is an inhibitor of CYP3A4 receptors.
ADVERSE EFFECTS: ⏤ Use: diarrhea and

1. Gastrointestinal effects (nausea, gastrointestinal intestinal spasms
(serotonin-secreting
upset, diarrhea) carcinoid tumors and
2. Sexual effects- dec. loss of libido, delayed orgasm, postgastrectomy
or diminished arousal dumping
syndrome)
3. Increase in headaches and insomnia or
hypersomnia Ketanserin ⏤ 5HT2-receptor
4. Discontinuation syndrome (dizziness, paresthesias) (Sufrexal) antagonist
5. paroxetine is a category D agent.
⏤ it also antagonizes
alpha- adrenergic, H1-,
Serotonin syndrome and
● diagnosed on the basis of a history of dopamine receptors.
administration of a serotonergic drug within
⏤ Use: Antihypertensive
recent weeks and physical findings (Europe),
● It has some characteristics in common with Antihypertensive
neuroleptic malignant syndrome (NMS) and and for vasospastic
cond (USA)
malignant hyperthermia (MH)
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Clozapine ⏤ 5HT2A- and 5HT2C
(Clozaril) → receptor antagonist.
Risperidone
(Risperdal, ⏤ Clozapine → also
Risdin) block D4 receptor
⏤ Risperidone → also
block D2
receptor
Use: Antipsychotic
agents
SETRONS ⏤ 5-HT3 antagonists
This includes ⏤ Clinical use: mgt. of

chemotherapy induced
• Ondansetron nausea & vomiting
(Zofran)
• Granisetron
(Kytril)
• Palonosetron
• Alosetron
Vomiting
= the expulsion of gastric contents
Causes:
motion sickness, viral & bacterial infection, food intolerance,
surgery, PG, pain, shock, effects of some drugs, radiation, &
Anti-emetics
disturbances of the middle ear affecting equilibrium.
They are useful in the treatment of vomiting associated
with motion sickness (OTC) and chemotherapy (Rx)
Antiemetics can mask the cause & should not be used until
cause is determined, unless vomiting is severe enough to
cause dehydration & electrolyte imbalance. Anti-emetics Details Brands
Anticholinergic Scopolamine (Hyoscine)=

(came from the Hyoscyamus niger
Emesis or henbane
plants)
Triggered by “vomiting center” at the medulla
MOA:
Antagonize receptor of
Four important sources of afferent input (neurons that
acetylcholine receptor
carry sensory stimuli) to the vomiting center: they reduce the excitability Buscopan
of labyrinth in muscarinic (OTC)
1. chemoreceptor trigger zone receptors and depress the
conduction from the
2. vestibular system (important in motion sickness) vestibular apparatus to
3. Irritation of the gastrointestinal mucosa by the vomiting center
chemotherapy, radiation therapy, distention, or acute
infectious gastroenteritis USE:
treat motion sickness
4. central nervous system
and in preoperative
operation
A/E: Drowsiness, dry

mouth, and blurred
vision
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Antihistamines •Diphenhydramine Cannabinoids ⏤ Dronabinol (Marinol)
• Meclizine ⏤ Nabilone (synthetic
• Cyclizine (Synthetic THC derivative)
•Dimenhydrina te Analog)
•Promethazine THC-psychoacti MOA: may act by
ve inhibiting the vomiting
component of center
MOA: Marijuana
act by inhibiting USE: chemotherapy
cholinergic pathways of induced nausea
the vestibular apparatus administered either as
by receptor crossover an oral preparation
or smoked as a cigarette
USES: motion sickness, (if other drug is
true vertigo and nausea ineffective only)
in pregnancy
A/E:
A/E: sedation and dry sedation, psychoactive
mouth effects, dry mouth
and orthostatic
Dopamine Dopamine receptor hypotension
Antagonists (D2) blockade
Glucocorticoids Example:
→ blocks the dopamine Dexamethasone and
receptors in the CTZ Betamethasone
Metoclopramide Methylprednisolone
(Plasil) USE: (Solu-medrol)
→ Used to treat nausea
Domperidone due to chemotherapy
(Motilium) (use of cisplatin and Use: can be effective as
doxorubicin) and a treatment for
narcotic induced vomiting caused by
vomiting highly emetic agents.
high doses are given as
(Metoclopramide) an intravenous bolus or
→ Motion sickness orally for delayed
(Domperidone) nausea often combined
with other anti-emetics
A/E: A/E:
⏤ Sedation may cause adrenal
⏤ Diarrhea suppression and
⏤ extrapyramidal effects metabolic disturbances
⏤ elevated prolactin
secretion Benzodiazepine Lorazepam (Ativan)
Diazepam (Valium)
This includes Granisetron
• Ondansetron ⏤ has a greater affinity MOA: GABA Agonist
(Zofran) for 5-HT3 receptors than
• Granisetron ondansetron Uses:
(Kytril) → Acts as anxiolytic
• Palonosetron ⏤ longer acting and agents to reduce
• Alosetron more potent than anticipatory emesis
ondansetron or → diazepam is useful as
metoclopramide a treatment for vertigo
and it controls symptoms
⏤ most common adverse of Meniere’s disease
effect is headache
A/E:
Carisma II 21
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ipecac is noted in abusers such as bulimics
anterograde amnesia
which lasts for 4-6 hrs ⏤ Persistent vomiting (eg, acetylcysteine)
⏤ hemorrhagic gastritis or Mallory-Weiss tear.
Aprepitant MOA:
Neurokinin receptor
antagonist 2. APOMORPHINE
Central blocker of area The only opioid derivative not classified as
postrema narcotic analgesic.
It also inhibits substance
P
USE: MOA:
→ combination with ⏤ Dopamine agonist
5HT3 blocker and ⏤ directly stimulates the CTZ
corticosteroids for acute Administered parenterally (SQ)
and delayed N & V
associated with
chemotherapeutic More toxic than ipecac
agents → it causes CNS and respiratory depression., therefore it
Enzyme inhibitor is not widely used.
(CYP3A4)
Emetics
→ Used for antidote
Agents that induce reflex vomiting
1. IPECAC
mixture of alkaloids including
emetine andcephaeline derived
from the ipecacuanha plant.
MOA:
induces vomiting by stimulating the
CTZ and bycausing GIT irritation
and afferent input to the vomiting
center
administered orallyfast acting, causing

vomiting in 85% of the patients within 20
minutes useful in removing unabsorbed toxins from the
stomach.
CONTRAINDICATIONS:
⏤ Coma
⏤ Absence of the gag reflex
⏤ ingestion of caustic agents and
petroleum
distillates
Adverse Effects:
⏤ cardiac toxicity caused by emetine in
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Week 4(B): Pharmacology of Motility Disorder
Physiology of Defecation Constipation

→ accumulation of hard fecal
→ It is also known as a bowel movement, the process in material
which weight are usually removed once or twice daily. in the large intestine
→ It is controlled by neurological reflexes and sphincters

It is a major problem of among the
found in our large intestine; thus, it ordinarily occurs only
elderly (reduce muscle tone and
in appropriate circumstances and times.
weaker peristalsis)
Filling of meal triggers
gastrocolic reflex.
Pathophysiology:
When you wake after sleep, • Constipation commonly results
stretching and,sitting and from a diet low in fiber or from use of constipating
then standing- orthocolic drugs such as opiates.
reflex This reflexes results
to muscle contraction in
• Constipation may sometimes be psychogenic in
the colon.
origin
Muscle contraction also
results to stretch of rectum CAUSES :
called defecation reflex- account to urge to defecate ● poor H2O intake & poor dietary habits
(advisable to take plenty of water and also eat
2 types: food that are reach of fiber)
Internal defecation reflex- controlled by Enteric ● ignoring the urge
Nervous System (myenteric plexus)
● fecal impaction
● bowel obstruction
Parasympathetic defecation reflex controlled by
Parasympathetic Nervous System (transmitted to the
● chronic laxative use
spinal cord). ● neurologic disorders (paraplegia)
The Large Intestine Drugs Causing Constipation

• aka Colon
• 3-5 ft long • Analgesics
• Muscle contraction → cause motility, helping the Inhibitors of prostaglandin synthesis
stool move through and out the body. Opiates (Narcotics analgesic)
• Anticholinergics (Drugs that inhibit the parasympathetic
Functions:
nervous system → it is important to have a defecation
1. Absorbs salt
reflex)
and water from
Antihistamines
waste
2. Moving
Antiparkinsonian agents (e.g., benztropine or
waste/feces trihexyphenidyl)
3. Storing waste Pheothhiazines
4. Evacuating the Tricyclic antidepressants
waste through • Antacids containing calcium carbonate or
defecation aluminum hydroxide
• Barium sulfate ( Radiographic contrast media)
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Calcium channel blockers Laxatives
Clonidine
Diuretics (non potassium-sparing) Promote and facilitate bowel evacuation by:
Ganglionic blockers • Acting locally to stimulate intestinal peristalsis
Iron preparations • To soften bowel contents or both
Muscle blockers (D-tubocurarine, succinylcholine) - They are not only use for constipation but also use for the following
Nonsteroidal antiinflammatory agents condition or situation
Polystyrene sodium sulfonate

Uses:
1. Ease defecation in patients with painful hemorrhoids or
Signs and Symptoms:
other rectal disorder.
1. Infrequent bowel movements
2. Avoid potentially hazardous rises in blood pressure during
2. Stool of insufficient size defecation in patients with hypertension, cerebral arterial
3. Hard, small dry stools diseases.
4. Feeling of fullness(bloated stomach) 3. Relieve acute constipation.
5. Abdominal pain and discomfort 4. Remove solid material from the intestinal tract
6. Difficulty and pain on passing stool prior to certain roentgenographic studies.
7. Fatigue and headache
8. Nausea and vomiting Bulk-forming Laxatives
• Insoluble and non-absorbable substances that expand on

taking up water in the bowel
• Consist of polysaccharides and cellulose
derivatives that are undigestible. Because they absorb water,
they increase the bulk of stool and, in so doing, provide a
physiological stimulus to defecation.
Examples and Uses:

A. Dietary fiber (10-15g/day) Bran, linseed
Diagnosis: B. Hydrophilic colloids Psyllium (C-lium), karaya gum
• Proctoscopy, sigmoidoscopy, colonoscopy C. Synthetic fiber polycarbophil
• Barium enema- necessary to determine presence of D. Cellulose derivatives methylcellulose (Citrucel)
colorectal pathology USE: management of chronic constipation. Produce
• Thyroid function test → determine presence of laxation after 2-4 days and adequate hydration is
metabolic disorder that may cause constipation. required.
Non-Pharmacologic treatment Osmotic Laxatives

Soluble but non-absorbable particles that retain
Diet that contains fiber (whole grains, vegetable such water in the bowel by virtue of their osmotic action
as broccoli, carrots and sweetcorn and fruits such as and cause a reflex increase in peristalsis.
berries, pears, orange and pineapple)
Water A. Salt containing
Exercise → Also known as saline purgatives
Routine bowel habits (normal can be 1- • Magnesium sulfate- Epsom salt
3/day or 3/wk – varies from person to person) The • Magnesium citrate- Citrate of Magnesia
freq. is secondary to consistency – feces hard & dry. • Sodium phosphate- Fleet Enema
Stretching after waking up Eating breakfast (30-45 • Sodium sulfate- Glauber’s salt
mins after waking up) • Potassium sodium tartrate- Rochelle’s salt elicit a
watery bowel discharge 1–3 hrs after administration.
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General Uses:
Osmotic Laxative Details
1. for acute evacuation of the bowel before surgery
Magnesium The laxative action probably results or diagnostic procedures.
sulfate from two factors: 2. for elimination of parasites after antihelmhintic
Bitter salt; Epsom (1) SO4 ion administration.
salt → Not absorbed from the GI
tract and, thus, draws water into the
lumen of the bowel to make an Side effects:
isotonic solution and Magnesium containing → Hypermagnesemia
Caution: renally impaired patient
(2) Magnesium ion
Sodium containing → Hypernatremia
→ Release of cholecystokinin-pancre
Caution: Patients with CVD
ozymin, which causes an
accumulation of fluid and electrolytes
within the small intestine. Dehydration → adequate water intake is required
Oral → dissolve in iced water or B. Salt-free osmotic agents

orange juice to mask nauseous taste
• Lactulose
-laxatives
- bitter salt • Mannitol
• Sorbitol
IV →(125/500mg/ml) not as laxative, • Polyethylene glycol-electrolyte solutions
used to manage preeclampsia.
These agents maybe administered rectally
Sodium ⏤ One of the most palatable of the (glycerin) or orally (lactulose).
biphosphate saline laxatives
(NaH2PO4. H2O) ⏤ Its major use, however,
Laxative DETAILS
is for diagnostic procedures such
as proctoscopy, colonoscopy, or
Mannitol ❑ Osmotic laxative in oral doses
barium enema
larger than 20 g.
⏤ It also is used in the form of the
oral solution as an
❑ Mannitol I.V. (mannitol injection) is
antihypercalcemic.
a diuretic used to increase urine
production, and to treat or prevent
⏤ Used also in cystitis
(inflammation in the urinary bladder)
medical conditions that are caused
(combined with Methenamine) by an increase in body fluids/water
(e.g., cerebral edema, glaucoma,
Rectal solution → also known as kidney failure)
Fleet Enema
Oral solution → Fleet Mannitol: Injection - 5 %( 5mg/100ml), 10

Phospho-Soda %( 10mg/100ml), 15 %(15 mg/100ml),
20 % ( 20mg/100ml), 25 %( 12.5mg/50ml
Sodium sulfate ⏤ Used also as laxative to evacuate
Glauber’s salt bowel prior to surgery. Lactulose ⏤ cannot be hydrolyzed by digestive
Cholac®, enzymes
⏤ Used also electrolyte replenisher Lilac® ⏤ Fermentation of lactulose by colon
and is used in isosmotic solutions
so that administration does not
bacteria to lactic acid leads to
disturb normal electrolyte balance acidification of bowel contents and a
and does not lead to reduced number of bacteria.
absorption or excretion of water and ⏤ Depends on its breakdown by
ions colonic bacteria to carbon dioxide,
Carisma II 25
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prevention of straining at stool following surgery,
lactic acid, and small amounts of myocardial infarction, or stroke; and
acetic and formic acids, which acidify
provision of relief in painful diseases of the anus, e.g.,
the contents of the colon.
fissure, hemorrhoids.
⏤ The acidic environment converts
ammonia to ammonium
ion (NH4+), which cannot be
absorbed.
used in liver failure to forestall

hepatic coma by preventing
bacterial production of ammonia and
its subsequent absorption
(absorbable NH3 + - nonabsorbable NH4+).
Adverse Effect:
Flatus & cramps → gas generated in the Diphenylmethanes
stomach or bowels. due to fermentation
in the gut producing CO 2
Limitation to use:
Reabsorbed via enterohepatic circulation (biliary
Drug Interaction:
recycling) and have:
- If mataas ang enterohepatic circulation that means there is
▪ Neomycin → eliminate colonic
increase absorption and if tumatataas yung absorption tumataas
bacteria reducing the fermentation of rin yung effect nila into our body.
lactulose to lactic acid thus
decreasing the acidification of colon 1. increased risk of abuse and overdose
2. Cardiotoxic
Contraindication:
▪ Used with caution to patients with
diabetes (it contains monosaccharide 1 Bisacodyl converted by gut bacteria into the
molecule of galactose and 1 molecule of (Dulcolax) active colon-irritant principle.
fructose)
Given by the enteral route, bisacodyl
is subject to hydrolysis of acetyl
Stimulant Laxatives residues, absorption, conjugation in
liver to glucuronic acid (or also to
sulfate), and biliary secretion into the
→ Also known as Irritant Laxatives duodenum.
A. DIPHENYL METHANES Oral administration: 6–8 hours by

→ Phenolphthalein, bisacodyl Sodium picosulfate discharge of soft formed
B. ANTHRAQUINONES stool.
Suppository: bisacodyl effect (one
→ aloe, cascara sagrada and senna
hour)
C. CASTOR OIL
Phenolphthalein It tends to act longer than other
Mechanism of action: laxatives because it enters the
• Direct stimulation of the enteric nervous system and enterohepatic circulation and is
colonic electrolyte and fluid secretion. re-excreted in bile into the
• Have multiple actions on the intestine: Decreases intestine.
water absorption from the bowel lumen and stimulates
In susceptible individuals,
intestinal secretions. phenolphthalein may cause allergic
reactions, including SJS and lupus
USES: erythematosus.
Carisma II 26
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MOA:
It also may cause a Bartter’s-like Hydrolyzed to ricinoleic acid (upper GIT)à which
syndrome. stimulates water secretion the intestine while decreasing
The drug has been discontinued glucose absorption
Ricin
Chronic intake:
→ toxic component of castor bean can cause
• Disrupts the water and electrolyte balance of the
cardio toxic effect
body and can thus cause symptoms of illness (e. g.,
cardiac arrhythmias secondary to hypokalemia).
Oral administration: 10–30 ml of castor oil is followed
within 0.5–3 hours by discharge of a watery stool
• May also result in cathartic colon (melanosis coli)
Topical → emollient, stimulate hair growth
→ They are not advisable to be given for long term
Melanosis coli
→ is a condition usually associated with chronic laxative Stool Softener
use in which dark pigment is deposited in the lamina
propria (one of the lining layers) of the large intestine → Nonspecific stimulants or irritants
(colon).
The pigment deposition results in a characteristic dark • Also known as Emollient Laxatives
brown to black discoloration of the lining of the large
intestine. • Substances included in this category are surface-acting
or wetting agents, which are non absorbable and relatively
nontoxic
Anthraquinones
• Have a detergent action that facilitates the mixing
of watery and fatty substances to increase luminal mass
Laxative DETAILS
Mechanism of action: Their action is attributed to
Cascara sagrada From dried bark of Rhamnus purshiana their surface-active property:
Nature’s Remedy; Sacred Bark; Chittem;
Dogwood;Bearberry; Bitter Bark lowering surface tension permits the intestinal fluids to penetrate
the fecal mass more readily and produce soft, easily passed
• Widely used cathartic. stools.
• It is used for relief of transient
constipation. Examples Details
• It has very little action on the small
intestine but promotes peristalsis Docusate used to produce
in the large intestine (Colace, Surfak) short-term laxation and
Glycerin to reduce straining at
Sennosides Example: defecation.
Calcium sennosides (Senokot)
they are used to prevent
A natural complex of anthraquinone constipation.
glycosides found in senna, isolated
from Cassia angustifolia as calcium ⏤ almost non-absorbable
salts, contains 55% to 65% of the and makes feces softer
calcium salts. and passed easier and
coats fecal contents and
thereby inhibits
Castor Oil absorption of water
● obtained from the seed of Ricinus communis Linné (Fam ⏤ USE: prevent and treat
Euphorbiaceae) fecal impaction in
● Brand: Emulsoil; Neoloid; Purge children and debiliated
adults
Carisma II 27
__________________________________________________________________________________________________
⏤ Decreases the
absorption of fat soluble Clinical Presentation of Diarrhea
vitamins (long-term use)
and causes lipid General: Usually acute diarrheal episodes within 72
pneumonitis can develop hours of onset, whereas chronic diarrhea involves
if aspirated
frequent attacks over extended time periods.
Signs and Symptoms

Serotonin Agonist Abrupt onset of nausea, vomiting, abdominal pain,
headache, fever, chills, and malaise.
→ Prokinetic agents Bowel movements are frequent and never bloody,
and diarrhea lasts 12-60 hours.
MOA:
⏤ Stimulation of 5HT4 also activates cAMP
dependent chloride secretion from the colon, leading
to increased stool liquidity
⏤ Promotes gastric emptying and enhances
small and large bowel transit
Taken before meals

NOT be given to patients with severe hepatic or renal
impairment
USES:
For chronic constipation
Irritable bowel syndrome with constipation
Diarrhea
Excessive fluid weight, with 200 g/day representing Can cause minor or severe dehydration & electrolyte
the upper limit of normal stool water weight for imbalance
healthy adults Nonpharm treatment:
1. Clear liquids & oral soln’s (gatorade, pedialyte)
Manifested by:
• frequent liquid stool discharge • intended as soon as intake of usual foods and
• Increase frequency and decreased consistency of fluids is discontinued and before serious fluid looses
fecal discharge. or deficit occurs.
• Decrease transit time for Gastric emptying
• avoid non-clear liquids such as milk, juices, and
It can be life threatening to the young & elderly sodas, because these can actually make the diarrhea
Can be mild to severe - Identify underlying causes first. worse.
Causes: 2. IV electrolyte soln’s.

1. Foods Ringers Injection USP: (NaCl, KCl and CaCl2)
2. Bacteria & virus Lactated Ringers Injection USP: (NaCl, KCl, CaCl2 and
3. Drug reaction (antacids containing magnesium, Na lactate)
antibiotics, cholinergic drugs)
4. Laxative abuse, malabsorption syndrome, stress, Oral rehydration salts
bowel tumor, inflammatory bowel disease.
1. Balanced salt solutions containing glucose,
sucrose or rice powder
Carisma II 28
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2. Increase water absorption from the bowel lumen by
electrolyte movement
increasing sodium substrate transport across intestinal through the bowel.
epithelial cells.
Essentially free of CNS
3. Can remedy 99% of acute cases of childhood diarrhea. effects
Caution should
Antidiarrheal be used in patients with:
⏤ ulcerative colitis
⏤ Decrease fecal water content by increasing solute ⏤ Crohn’s colitis
absorption and decreasing intestinal secretion. ⏤ pseudomembranous
colitis who are at
⏤ Decrease motility and increased transit time increased risk for toxic
megacolon.
facilitates water reabsorption.
⏤ Also, loperamide may
prolong the course of
Opiates & Opioids infectious diarrhea
1. Opium tinctures
2. camphorated opium tincture Anticholinergics Examples:
3. Codeine 1. Atropine
2. Scopolamine
3. Methantheline
MOA:
4. Propantheline
→ Acts directly on opiate μ receptors
- decrease transit rate • Agents that inhibit colonic
-stimulate segmental contraction peristalsis by blocking the
- inhibit longitudinal contraction receptors of intestinal Smooth
They also stimulate electrolyte absorption muscle to cholinergic stimulation.
• Antispasmodics → Used to
A/E:
reduce colonic cramping
• nausea, sedation, vomiting (abdominal cramps)
• high doses may control refractory diarrhea,
resulting in a potential for dependence. • They have little effect on
diarrhea.
A. NON SPECIFIC ANTIDIARRHEALS
Adsorbents ⏤ kaolin and pectin and dietary
fiber
Diphenoxylate
⏤ Act by adsorbing toxic
• A synthetic analog of morphine compounds from intestinal water
• Combined with atropine to reduce the potential for ⏤ They are non-toxic but they are
abuse and to further reduce motility (Lomotil) less effective than other
agents.
Opiates & Opioids
⏤ Caution should be used in patients with ulcerative KAOLIN
Light Kaolin; White Bole;
colitis and pseudomembranous colitis who are at
Kaolin-Pectin Suspension
increased risk of developing toxic megacolon. A native hydrated aluminum
⏤ Also, it may prolong infectious diarrhea silicate.
S/E: nausea, sedation, vertigo, vomiting, pruritus, PECTIN

skin eruption, insomnia, and abdominal cramps. • A purified carbohydrate product
obtained from the dilute
acid extract of the inner portion of
Loperamide (Lomotil, MOA: binds to the the rind of citrus fruits or
Imodium, Diatabs) opiate receptor in the from apple pomace.
gut wall. acts by slowing • Metals, particularly the heavy
intestinal motility and metals, form insoluble
by affecting water and derivatives
Carisma II 29
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Bismuth • Binds to toxins produced by Irritable Bowel Syndrome (IBS)
subsalicylate Vibrio cholerae and E. coli
• Can be absorbed across the Idiopathic (unknown cause), chronic,
intestine relapsing disorder (reoccurring) characterized by:
• Inhibits the production of • Abdominal discomfort (pain, bloating, distention, or
prostaglandins in the intestine
cramps)
and reduces secretion
Use: Effective for both treatment • Alterations in bowel habit (diarrhea, constipation or both)
and prophylaxis of traveler’s
diarrhea Types:
1. Crohn’s disease
Adverse effect: Tinnitus ❑ inflammatory bowel disease that causes
chronic inflammation of the
gastrointestinal tract
B. ANTIDIARRHEALS FOR SPECIFIC CASES ❑ most commonly affects the colon and the last part of
the small intestine (ileum).
Octreotide • a synthetic 8-amino acid analog
of somatostatin
• used in cases of severe 2. Ulcerative colitis
diarrhea caused by excessive ❑ an inflammatory bowel disease (IBD) that causes
release of gastrointestinal tract inflammation and ulcers (sores) in your digestive
hormones including gastrin, tract.
motilin, vasoactive intestinal ❑ Affects the innermost lining of your large
polypeptide, glucagons and intestine (colon) and rectum. Symptoms usually
others
develop over time, rather than suddenly.
Tegaserod Serotonin (5HT4) Agonist
3. Pseudomembranous colitis
USE: short term tx of IBS with ❑ swelling or inflammation of the
constipation large intestine (colon) due to an overgrowth of
Clostridium difficile (C difficile) bacteria
Mesalamine & • Acts within the colon to limit
Olsalazine prostaglandin and leukotriene ❑ Clindamycin
production
→ antibiotic that causes the overgrowth
Use: ❑ Vancomycin and Metronidazole
• For the treatment of mild to → used in the management
moderate ulcerative colitis
Treatment for
• Olsalazine is approved for
maintenance of remission but not Irritable Bowel Syndrome (IBS)
treatment of this disorder
1. Antispasmodics → Relieve abdominal pain
Glucocorticoid Prednisone 2. Diarrhea: antidiarrheal agents
• Stimulates sodium absorption in • Mesalamine & Olsalazine→ ulcerative colitis
the jejunum, ileum and colon • Glucocorticoids → Chron’s disease
3. Constipation
• Used to treat refractory diarrhea
unresponsive to other agents and • fibers, milk of magnesia
chronic inflammatory bowel • Tegasaerod- Serotonin (5HT4) Agonist
disease (Crohn’s • SSRIs → Selective Serotonin Reuptake Inhibitors
disease
4. Chronic abdominal pain:
TCA (amitriptyline, desipramine 10-50mg/d)
Doses typically begin low and can gradually increase if
needed. These low doses are usually not at a therapeutic
dose to manage depression or anxiety.
Carisma II 30
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Week 5: Pharmacology of Eicosanoids -vasopeptidase
Eicosanoids
→ are a large group of autacoids with potent effects on

virtually every tissue in the body.
→ These agents are derived from metabolism of

20-carbon, unsaturated fatty acids (eicosanoic acids).
The eicosanoids
include:
1. Prostaglandins
2. Thromboxanes
3. Leukotrienes
4. Hydroperoxyeicosatetraenoic acids (HPETEs)
5. Hydroxyeicosatetraenoic acids (HETEs).
Biosynthesis of Eicosanoids
Prostaglandin–H–synthase Pathway
Arachidonic acid, (5,8,11,14-eicosatetraenoic acid) the
most common precursor of the eicosanoids, is This pathway make use of COX
formed by two pathways This produces:
1. Thromboxane
● Phospholipase A2 → mediated production from 2. Primary prostaglandins (PGE, PGF, PGD, PGI2)
membrane phospholipids.
● Phospholipase C in concert with diglyceride COX-1 enzyme COX-2 enzyme
lipase can also produce free arachidonate
Distribution This is located in Found in great
endothelial cells, abundance in
kidney,gastrointestinal Connective
tract, and many other tissues.
Expression Expressed at fairly It is highly

constant levels inducible by
numerous
Following irritation or injury Arachidonic acid is released PGH synthase-1 factors associated
(COX-1) is expressed with inflammation.
from cell membranes. constitutively in most
cells.
Pathways of Arachidonic Acid
→ Prostaglandin H synthase (COX) pathway Function Generates prostanoids Current theories
for “housekeeping” suggest that
→ Lipoxygenase pathway (LOX) such as gastric the type 2 isoforms
epithelial cytoprotection is predominantly
Various eicosanoids are synthesized throughout the associated with
eicosanoids
body. Synthesis can be very tissue-specific.
production in
inflammation.
Carisma II 31
__________________________________________________________________________________________________
COX-1 enzyme is also known as PGH synthase-1.
While COX-2 enzyme is also known as PGH synthase-2.
COX-1 is constitutive and it is always present in the body.

On the other hand, COX-2 is an inducible enzyme that can only be
produced in situations where inflammation occurs in the body.
Pharmacologic Action of Eicosanoids
The eicosanoids all have short plasma half-lives

(typically 0.5-5 minutes). Most catabolism occurs in
the lung.
● Prostaglandins are metabolized by PDGH to
15-keto metabolites.
● Thromboxane A2 (TXA2) is rapidly hydrated to
the less active TXB2.
● PGI2 is hydrolyzed to 6-keto-PGF.
Lipoxygenase Pathway
● This produces the HPETEs, HETEs, and the

leukotrienes.
● Additional metabolites of the HPETEs,
hepoxillinsm and lipoxins, have been identified, but
their biological roles is unclear.
This pathway is of great interest since it is associated

with asthma, anaphylactic shock, and cardiovascular
disease
LTC 4 and LTD 4 > primary components of the

slow-reacting substance of anaphylaxis (SRS-A)
Carisma II 32
__________________________________________________________________________________________________
Synthetic Analogs
Most common Adverse Effect:
Synthetic Analogs Details Brand NSAIDs (Non-steroidal Anti-inflammatory Drugs)
Misoprostol ⏤ PGE1 analogue

(Cytotec) ⏤ Used as
cryoprotectant
⏤ approved for use in

patients taking high COX-2-Selective Inhibitors “Coxibs”
doses of nonsteroidal
anti-inflammatory
drugs (NSAIDs) to
reduce gastric
ulceration.
A/E: Uterine
contraction Dietary Manipulation
(Abortifacient) of Arachidonic acid
Dinoprostone ⏤ PGE2 analogue Changing the phospholipid composition of cell

(Prepidil, ⏤ Used for abortion membranes by replacing arachidonic acid with
Cervidil) and cervical ripening
the dietary fatty acids:
combined with
mifepristone Linoleic acid → corn, safflower, and sunflower oils
(RU486) to induce
first-trimester abortion Eicosapentaenoic (C20:5)
Latanoprost ⏤ PGF2α analogue Docosahexaenoic acid (C22:6)

(Xalatan) ⏤ Used in the
management of ● called omega-3 fatty acids
glaucoma
A/E: irreversible ● from cold-water fish.

brown pigmentation
of the iris and
eyelashes
Dietary uses:
1. Reduction in the incidence of myocardial

infarction and sudden cardiac death
2. Protect against experimentally induced

arrhythmogenesis, platelet aggregation, vasomotor
spasm, and dyslipidemias.
Carisma II 33
__________________________________________________________________________________________________
catalyzes the cleavage of dipeptides from the
Vasoactive Peptides carboxyl terminal of certain peptides.
→ Vasoactive peptides are autacoids with significant
a.k.a. “Peptidyl Dipeptidase” or “Kininase II”
actions on vascular smooth muscle as well as other
tissues. They include vasoconstrictors, vasodilators, Angiotensin II
and peptides with mixed effects.
→ is an octapeptide that is converted from
Vasoactive Peptides Angiotensin Angiotensin I (AI) through removal of two
→ a peptide, causes blood vessels to constrict, and C-terminal residues by the enzyme
drives blood pressure up. angiotensin-converting enzyme (ACE), primarily
through ACE within the lung.
→ it is part of the renin-angiotensin system, which is a
major target for drugs that lower blood pressure. Actions of Angiotensin II
→ It stimulates aldosterone from cortex. Aldosteroneπ 1.Blood Pressure

promotes release the adrenal sodium retention in the
distal nephron, in the kidney, which also drives blood → Increase the release of epinephrine and
pressure up. norepinephrine.
2.Adrenal Cortex
Angiotensinogen
→ it is synthesized in the liver. → Acts directly on the zona glomerulosa to
stimulate aldosterone biosynthesis.
→ a serum α2-globulin secreted in the liver which, on
hydrolysis by renin, gives rise to angiotensin. 3.Kidney
→production is increased by corticosteroids,estrogens, → cause renal vasoconstriction, increase proximal

tubular inhibit sodium reninreabsorption, and
thyroid.
secretion.
Renin 4. Central Nervous System

→ is an aspartyl protease catalyzes the hydrolytic
release of the decapeptide angiotensin I from → Stimulate drinking (dispogenic effect) and
angiotensinogen, increase the secretion of vasopressin, and
adrenocorticotropic hormone (ACTH).
→ it is synthesized as a preprohormone that is
5. Cell Growth
processed to prorenin, which is inactive, and then
to active renin, a glycoprotein, consisting of → a mitogenic for vascular and cardiac muscle
340 amino acids. cells and may contribute to the development of
cardiovascular hypertrophy
Angiotensin I
Drugs that block Renin Secretion
→ It acted on the plasma or tissue
aminopeptidases to form angiotensin I; this in turn ● Clonidine
is converted to angiotensin II by converting ● Propranolol
enzyme.
Renin Inhibitors
Converting Enzyme
● Remikiren
→Is a dipeptidyl carboxypeptidase that ● Enalkiren
● Aliskiren
Carisma II 34
__________________________________________________________________________________________________
Forms of Kininogens
Angiotensin Converting Enzyme
1. Low-Molecular Weight Kininogen
(ACE) Inhibitors
→ Crosses capillary walls
→ Captopril & Enalapril are the prototype agents. 2. High-Molecular Weight Kininogen
→ Confined to the bloodstream and serve
• Lisinopril as the substrate for plasma kallikrein.
• Benazapril
• Fosinopril Actions of Kinins
• Perindopril 1. Effects on the Cardiovascular System
• Ramipril → produce marked vasodilation in several beds,
• Moexipril including the heart, kidney, intestine, skeletal
• Quinapril muscle, and liver.
• Trandolapr
2. Effects on Endocrine and Exocrine
Angiotensin Receptor Blocking Glands
Agents
→ Losartan & Valsartan were the first marketed blockers of → Modulate the tone of pancreatic ducts and
angiotensin II type 1 (AT1) receptor. salivary and help regulate gastrointestinal.
• Candesartan 3. Role in Inflammation

• Eprosartan
→ Kallikreins and redness (rubor), kinins
• Irbesartan
local can produce heat (calor),swelling (tumor), and
• Telmisartan pain (dolor), and the production of kinins is
increased in inflammatory lesions.
• Kinins
4. Effects on Sensory Nerves
→ Formed enzymatically by the action of enzymes → Are potent pain-producing substances when
known as kallikreins or kininogenases acting on applied to a blister base or injected intradermally.
protein substrates called kininogens.
Metabolism of Kinins
1. Kinnase I
→ Potent vasodilator peptides. → Synthesized in carboxypeptidase the liver,is
a that releases the carboxyl terminal arginine
• Kallikreins residue.
→ produced in the liver as pre kallikreins and
present in plasma and in several tissues, including 2. Kinnase II
the kidneys, pancreas, intestine, sweat glands, and → Present in plasma and vascular endothelial cells
salivary glands. throughout the body.
→ They are serine proteases with active sites and Drugs Affecting the Kallikrein-Kinin System
catalytic properties similar to those of enzymes such
trypsin, chymotrypsin, elastase, thrombin, plasmin, 1. Icatibant
and other serine proteases. → second generation B2 receptor antagonist.
→ Used to evaluate the role of kinins in pain,
• Kallikreins hyperalgesia, and inflammation.
→ The precursor of kinins and substrates of
kallikreins which are present in plasma, lymph, and 2. 3rd Generation B2 Receptor Antagonist
interstitial fluid. FR 173657
FR 172357
NPC 18884
→ Inhibit bradykinin-induced bronchoconstriction
Carisma II 35
__________________________________________________________________________________________________
• Vasopressins
→ a.k.a. “Antidiuretic Hormone”. Endothelins
Its two primary functions are to retain water in the body → are proteins that constrict blood vessels and
and to constrict blood vessels. raise blood pressure.
• Terlipressin (triglycyl lysine vasopressin)

→ more selective for V 1 receptors and has a longer Physiologic and Pathologic Roles of
half-life. Endothelins
• Essential Hypertension
Vasopressin Antagonist • Cardiac Hypertrophy
• Heart Failure
V1a receptor antagonists • Atherosclerosis
• relcovaptan • Coronary Artery Disease
• conivaptan • Myocardial Infarction
→ approved for treatment of hyponatremia • Pulmonary
• Hypertension
Others: • Asthma
Lithium
Demeclocyline
Vasoactive Intestinal Peptides (VIP)
Natriuretic Peptides → a peptide hormone.
→ It produces marked vasodilation in most
→ one of the peptides that causes natriuresis, the vascular beds Causes exerts coronary
excretion of an excessively large amount of positive vasodilation and inotropic and
sodium in the urine. The natriuretic peptides are chronotropic effect.
produced by the heart and vasculature:
Substance P
• A-type natriuretic peptide → is a neuropeptide: an undecapeptide that
→ is secreted largely by the atrial myocardium in response functions as a neurotransmitter and as a
to dilatation. neuromodulator.
• B-type natriuretic peptide → It belongs to the tachykinin neuropeptide family.

→ is manufactured mainly by the ventricular myocardium.
It useful in thediagnosis of heart failure. The finding of a • Substance P is an important element in
low level of B-type natriuretic peptide tends to exclude pain perception.
heart failure.
• Substance P also has effects as a potent
• C-type natriuretic peptide vasodilator.
→ is produced by endothelial cells that line the blood
vessels. Tachykinin receptors
NK 1
Vasopeptidase Inhibitors NK 2
→ are new class of cardiovascular drugs that inhibit two NK 3
metalloprotease enzymes, NEP 24.11 and ACE. aprepitant
• Omapatrilat • first antagonist approved for the prevention of
• Sampatrilat chemotherapy-induced nausea and vomiting.
• Fasidotrilat
Carisma II 36
__________________________________________________________________________________________________
• Neurotensin
→ is a tridecapeptide that was first isolated from the The main effect is increased food intake and
central nervous system but subsequently found to be decreased physical activity.
present in the gastrointestinal tract and in the circulation.
• Urotensin
→ It is synthesized as part of a larger precursor that also → Was originally identified in fish, but isoforms are
contains neuromedin N, a six-amino-acid neurotensin-like now known to be present in mammalian species
peptide. including mouse, rat, pig, and human.
Modulates neurotransmission → In vitro, it is a potent constrictor of vascular

agonist and used for smooth muscle.
Parkinson’ s Disease.
→Occurs primarily in arterial vessels, where
Neurotensin urotensin II can be more potent than
schizophrenia endothelin 1.
Increase levels in patients with
• Calcitonin Gene-Related Peptide

→ Is a member of the calcitonin family of peptides which
also includes calcitonin, adrenomedullin and amylin.
→ Causes hypotension and tachycardia (inj. In systemic
circulation)
→ Play a role in pathophysiology of migraine.
• Adrenomedullin
→ discovered in human adrenal medullary
pheochromocytoma tissue.
→ Presents in several organs including adrenals, lungs,

heart, vascular tissue, and kidneys.
→ Elevated in patients with hypertension, as well as in

patients with renal failure, heart failure, and septic
shock.
•Neuropeptide Y [NPY]
→ Is a member of the family that also includes
peptide YY and pancreatic polypeptide.
→ Each peptide contains of 36 amino acids.
→ One of the most abundant neuropeptides in both the

central and nervous peripheral system.
NPY has been associated with a number of physiologic

processes in the brain, including the regulation of energy
balance, memory and learning, and epilepsy.
Carisma II 37

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OLFU College of Pharmacy (Laguna Campus) Prelim Term

PCOL211 - PHARMACOLOGY 1 Second Semester

Week 2: Review of Pharmacodynamics

• Pharmacodynamics B. Target protein mediated mechanism

→ “what the drug does to the body” a. Structural Proteins

Acetylcholinesterase - Edrophonium GABA receptors control Cl- ions stimulated by:

2.4 Receptors • GTP-binding signal transducer protein is G-Protein

1. Type I Receptor Examples of Type II receptors

Imatinib → gastrointestinal stromal tumors (GIST)

4. Type IV Receptor - “gene transcription-linked receptors” Theories of Drug Receptor Interaction

location: nucleus/cytosol (cytoplasm) • Occupancy Theory

Drugs that act on Type IV receptors • Rate Theory

Receptor Interactions Types of Receptor Action

2. Lock and Key Theory 1. Down Regulation

→ result of down-regulation; effect of

3. Induced-Fit Theory 3. Sensitization or Up-regulation

➔ It is the magnitude or the intensity of the C. Shape of Dose-Response Curves

→ a. k. a. “Intrinsic Activity” Steep dose-response curves in patients could result

→ is a measure of drug activity expressed in terms • Quantal Dose-Response Curve

Quantal dose-effect curves

IV Delayed-Type •Contact Dermatitis T-cells

V Autoimmune •Grave‟sDisease IgM or

4. PATHOLOGICAL FACTORS 1.1 PHARMACODYNAMIC ANTAGONIST

Classification of drugs according to receptor interaction

1.2 PHARMACOKINETIC ANTAGONIST

→ Eg. Digoxin + Cholestyramine

e.g. HISTAMINE + EPINEPHRINE

1. Full Agonist 3. CHEMICAL ANTAGONIST

Protamine- (+) charged at physiologic pH

1. Pharmacologic Antagonism Chelating agents

Example: Phenoxybenzamine Experimental Method or Target Organ: Respiratory effects

Types of Allosteric Modulation Goals of preclinical studies

1. Positive Allosteric Modulation • identifying all potential human toxicities;

2. Negative Allosteric Modulation 1. "no-effect" dose → the maximum dose at which a

Determination of the ff.

Week 3: AUTACOIDS- HISTAMINE

2. Lipid derived autacoids ( Eicosanoids)

4. Vasoactive polypeptides tubocurarine, guanethidine, and amine antibiotics.

H2 Gastric cAMP Dimaprit, Ranitidine,

A. Histamine (H1)-receptor antagonists

• Aka: “classical ANTIHISTAMINES”

CLASSES of Histamine (H1)-receptor antagonists

1. 1st Generation Antihistamines

HISTAMINE AGONISTS a. Ethanolamines: (antiemetics)

• block mucus secretion and sensory nerve Adverse Effects

• effective local anesthetics • sedation (synergistic w/ alcohol, other

• relax histamine-induced contraction of bronchial • gastrointestinal upset, nausea, constipation

• frequently cause CNS depression (1) Histamine (H2) → receptor antagonists

Inhibitors of histamine release: Duodenal Ulcers vs Gastric Ulcers

2. They inhibit the release of histamine and other

sedation No sedation • Helicobacter pylori

Complications of PUD • Prostaglandin analogue: Misoprostol

• Sucralfate (Iselpin®) (aluminum sucrose sulfate) Bismuth

Differences in the types of Antacids C. Antacids

Neutralizing capacity NOT USED ANYMORE FOR ITS DEMERITS

■ Combination products ■ 5. It inhibits secretion of some anterior pituitary hormones.

1. Combine fast and slow reacting antacids to

2. Lower the dose of each component and