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Shannon Hobson 242425

BIOP211 Pharmacology

Abbreviated Drug Monograph

By: Shannon Hobson

Student Number: 242425

Word count: 1100

Drug Monographs:

OCP, Warfarin, Paracetamol, and Beta-blockers

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Abstract:

A drug monograph as a document that outlines the class, indications, limitations, efficacy,

mechanism of action, cautions, contradictions, interactions, safety, as well as, the health

effects of a pharmaceutical drug. This report outlines 4 drug monographs, focusing on oral

contraceptive pills (specifically Triphasic formulation), Warfarin, Paracetamol, and beta-

blockers (specifically Carvedilol).

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Table of Contents:

Introduction, p.4

Drug Monographs

Oral Contraceptive Pill: Triphasic formulation, pp. 5-7

Warfarin, pp. 8-10

Paracetamol, pp. 11-13

Beta-blocker: Carvedilol, pp. 14-15

Conclusion, p.16

References, pp. 17-20

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Introduction:

The turnover for pharmaceutical companies here in Australia is estimated at a staggering

$23.4 billion (Australian Government 2014), and the one issue surrounding the heavy

reliance on pharmaceuticals is their risks versus rewards. This report outlines 4 drug

monographs; oral contraceptive pills (Triphasic formulation), Warfarin, Paracetamol, and

beta-blockers (Carvedilol). These monographs outline indications, mechanism of action,

efficacy and limitations, cautions/contradictions, as well as, adverse health effects that could

occur upon use. It’s important to note that there are alternatives to pharmaceutical drug use,

and that these drugs should not be considered a ‘cure-all’ solution.

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Drug Monographs:

1) Oral Contraception Pill: Triphasic formulation

Class: Combined oral contraceptive pill (MIMS Australia 2015)

Table 1.1: Examples and Active ingredients of Triphasic Formulations

Example Active Ingredients

Triphasil® Levonorgestrel, Ethinyl Estradiol

Ortho Tri-Cyclen® Norgestimate, Ethinyl Estradiol

Ortho Tri-Cyclen® Lo Norgestimate, Ethinyl Estradiol

*table information from The American Society of Health-System Pharmacists (2015)

Indications: Oral contraceptive or birth control pills are used to prevent pregnancy

(triphasic’s), and some are used to treat acne and reduce symptoms of premenstrual

dysphoric disorders (The American Society of Health-System Pharmacists 2015). A

randomised control trial by Byamugisha et al. (2010, p.670) outlined that the active

ingredients Levonorgestrel and Ethinyl Estradiol are used for emergency

contraception (EC).

Mechanism of Action: Oestrogens and progestin’s inhibit the release of follicle

stimulating and luteinizing hormones, thus not enabling the follicle to grow (West

Virginia University 2013). Progestin’s also alter the uterine lining, making it

inhospitable for implantation, as well, they increase cervical mucus which reduces

sperm motility (West Virginia University 2013).

Efficacy and limitations: A review by Grimes et al. (2009, p.13) determined that

triphasic formulations of oral contraceptive pills did have a slightly better outcome in

reducing pregnancies, as well as, having less break-through bleeding then

monophasics pill formulations. Although, WHO (2015) determined that triphasic

formulations did not have a significant advantage over monophasic formulations.

Also, a systematic review by Mansour et al. (2010, p.9) points out that triphasic

failure rates depend greatly on compliance with dosing regime and fecundity.

Cautions/contradictions: Use caution when combining triphastic oral contraceptive

with hepatic enzyme inducers, protease inhibitors, St. John’s Wort, CYP3A4

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inhibitors, beta-adrenergic antagonists, caffeine, competitive inhibitors of gastro-

intestinal sulfation, drugs that decrease gastro-intestinal transit time, anti-

hypertensive’s, anti-convulsant’s, anti-coagulants, and hypoglycaemic’s (MIMS

Australia 2015). The American Society of Health-System Pharmacists (2015) also

state to exercise caution if overweight, have a family history of breast cancer, may be

pregnant, or having surgery.

Table 1.2: Adverse effects

Source Adverse Health Effects

The American Society of Health-System Pharmacists (2015)

Outline that the oral contraception pill can

cause nausea, breast tenderness, mood

changes, break-through bleeding,

headaches, skin changes, change in

libido, and potential weight gain. Also,

possible serious adverse effects include

thrombosis and potential increased risk of

developing breast cancer.

Battaglia et al. (2014, p.478) This randomized control trial determined

that the active ingredient Ethinyl Estradiol

in birth control formulations caused a

reduction in female sexual libido,

specifically decreasing clitoral

vascularization and increasing vaginal

dryness, as well as, decreasing

testosterone levels.

Klipping et al. (2011, p.165) This open-label, randomized, crossover

study determined that an intake of a

ethinylestradiol/levonorgestrel formulation

showed adverse effects like headache

and nasopharyngitis among some

participants. Also,

ethinylestradiol/levonorgestrel formulation

showed an increase in D-dimer levels

and a more pronounced increase in

levels of prothrombin and fibrinogen, thus

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a slight increase to coagulation.

Ziller et al. (2014, p.417) Determined that there is a higher risk of

deep vein thrombosis when using

combined oral contraceptive pills. Also,

the use of pills containing Norgestimate

over Levonorgestrel did slightly increase

this risk.

2) Warfarin:

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Class: Anti-thrombotics, anticoagulants (MIMS Australia 2015)

Table 2.1: Examples and Active ingredients of Warfarin

Example Active Ingredients

Coumadin Warfarin sodium

Marevan Warfarin sodium

*table information from MIMS Australia 2015

Indications: Warfarin is used as a prophylactic and treatment for deep vein

thrombosis and pulmonary thromboembolism, associated with myocardial infraction,

atrial fibrillation or person’s with prosthetic heart valves (Bryant & Knights 2015,

p.580).

Mechanism of Action: Warfarin inhibits the synthesis of clotting factors, as well as,

C1 subunit of vitamin K (epoxide reductase enzyme complex), and thus reduces the

regeneration of vitamin K1 epoxide (MIMS Australia 2015). Warfarin also decreases

the amount of active form vitamin K dependent clotting factors by 30-50%, which are

made in the liver (MIMS Australia 2015).

Efficacy and limitations: Yuh-Jer Shen et al. (2008, p.818) outlines Warfarin’s lack

of efficacy in relation to use for noncardioembolic stroke in differing ethnic

populations. Schulman (2014, p.2) outlines that warfarin needs to be taken for longer

(5 days) to see maximum effects, as well it has a longer half-life (36-48 hours) in

comparison to new anti-coagulants, thus it takes longer for warfarin to reach a steady

state in the body, this could lead to adverse health effects if dosing is not correct.

Cautions/contradictions: Warfarin is known to have many drug and food

interactions; table 2.2 outlines these. MIMS (2015) states that Marevan and

Coumadin should not be interchanged. The Mayo Foundation for Medical Education

and Research (2015) states that person’s on warfarin need to have regular blood

tests to determine viscosity of blood for proper dosing. The Mayo Foundation for

Medical Education and Research (2015) also states that using warfarin during

pregnancy and lactation is not recommended, also that there is an increased risk of

bleeding if injury should occur. Table 2.3 outlines more of Warfarin’s cautions and

contradictions.

Table 2.2: Drug and Food Interactions with Warfarin

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Interactions with:

Antimicrobials, cardiovascular drugs, anti-inflammatories, immunodulators,

analgesic drugs, drugs for the gastrointestinal system, anti-neoplastic drugs

(Bryant & Knights 2015, p.580)

Food interactions: -Increased anti-coagulating effect seen with dong quai, St. John’s Wort,

garlic and papaya

-Decreased anti-coagulating effect seen with ginseng

(Bryant & Knights 2015, p.580)

Leafy green vegetables reduce warfarin’s anti-coagulating effects, thus

increasing the chances of clotting if eaten in high doses (Palo Alto Medical

Foundation 2009)

Ingestion of large amounts of cranberry juice and mangoes increases

warfarin’s effects and thus increases chance of bleeding (Palo Alto Medical

Foundation 2009)

Alcohol consumption over moderate intakes (over 2 drinks/day) increases

the risk of bleeding when on warfarin (Palo Alto Medical Foundation 2009)

Table 2.3: Other cautions and contradictions when using Warfarin

Other cautions/contradictions:

Use with caution in people with a history of allergic reactions (severe) or

anaphylaxis, oedema, high cholesterol, hypothyroidism, the elderly,

alcoholics, person’s on psychotics or the mentally unstable, blood

disorders, pericarditis, visceral cancer, liver and kidney impairment, vitamin

C deficiency, vitamin K deficiency, or endocarditis (Bryant & Knights 2015,

p.580)


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Yuh-Jer Shen et al. (2008, p.819) Outlines that warfarin is associated with a

greater bleeding risk then aspirin. As

well, this review determined that there

was a 2-fold increase to the risk of stroke

when on warfarin for people of colour.

Reddy et al. (2014, p.1991-1993) Adverse effects seen in this randomized

clinical trial were major bleeding, serious

pericardial effluence, stroke, and

cardiovascular or unexplained death.

Guidoni, Obreli-Neto & Leira Pereira (2014, p.547)

This study found that there was a high

incidence of excessive anticoagulation

and risk of bleeding in patients taking

warfarin.

Verret et al. (2012, p.876) Adverse effects seen, in this randomized

control trial, were ocular hematoma from

taking the wrong dosage amount, some

major bleeding events, gastrointestinal

bleeding associated with chronic

ulcerative colitis, and haematuria in post-

urologic surgery.

3) Paracetamol:

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Other name: Acetaminophen (The Mayo Foundation for Medical Education and

Research 2015)

Class: Analgesic and antipyretic (MIMS Australia 2015)

Dosage forms: Paracetamol dosage forms include capsules, oral powder, oral

liquid or suspension, soluble tablets and tablets (uncoated, film coated, effervescent

and gelatine coated) (Australian Government TGA 2014).

Indications: Paracetamol is used readily to relieve fevers, as well as, mild to

moderate pain, including use for headaches, period pain, otitis media (earache),

migraine, muscular pain/aches, postoperative pain and osteoarthritis (first-line

treatment) (Bryant & Knights 2015, p.67). Paracetamol can also be used for

toothache, sinus pain, back pain, arthritis, tennis elbow, colds, and flu (Australian

Government TGA 2014).

Mechanism of Action: Paracetamol’s mechanism of action is still not completely

understood (Marzuillo, Guarino & Barbi 2014, p.418). It is thought that paracetamol

has an inhibiting effect on prostaglandin synthesis in the brain, but it has been further

hypothesised that paracetamol activates the serotonergic inhibitory descending pain

pathway (central serotonergic mechanism). Also, it has been hypothesised that

paracetamol has an effect on cannabinoid receptors creating a paracetamol

metabolite fatty acid amide N-arachidonoylphenolamine, giving this drug the ability to

depolarize afferent neurons, causing the synthesis of nitric oxide within the spine and

having an inhibiting effect on nociceptive conduction (Marzuillo, Guarino & Barbi

2014, p.418).

Efficacy and limitations: A randomized comparative study by Vyas et al. (2014)

determined that paracetamol did have an antipyretic action, seen over a 4 hour

period, and having a 1.48% decrease in the temperature. Also, a randomized control

trial by Williams et al. (2014) showed that paracetamol did not show any

improvement to varying degrees of back pain versus the placebo treatment. As well,

a randomised noninferiority trail by Ghosh et al. (2013, p.440) determined that

differing dosages (1000mg/2 a day vs 500mg/4 times a day) of paracetamol did have

an analgesic and antipyretic effect.

Cautions/contradictions: Caution should be taken when giving paracetamol, as

person’s with renal or liver dysfunction could be adversely affected (Bryant & Knights

2015, p.67). The Mayo Foundation for Medical Education and Research (2015)

outlines that paracetamol should not be given to children under the age of 2, that

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paracetamol is considered safe for use during pregnancy, and has minimal risk

during breastfeeding. Paracetamol should be taken as per instructions as over-dose

can occur (The Mayo Foundation for Medical Education and Research 2015).

Paracetamol does interact with other medicines and other, which is outlined in table

2.1.

Table 3.1: Paracetamol drug and other interactions

Drug and Other Interactions:

Drugs/medicines: Imatinib

Isoniazid

Pixantrone

Pneumococcal 13-Valent Vaccine, Diphtheria Conjugate

Acenocoumarol

Carbamazepine

Fosphenytoin

Lixisenatide

Phenytoin

Warfarin

Zidovudine

Other: Ethanol

Tobacco

Cabbage

*table information from The Mayo Foundation for Medical Education and Research

(2015)



Marzuillo, Guarino & Barbi 2014, p.418

This study outlines that paracetamol can

potentially cause a rash or allergic

reaction in some people, but this rash

can become serious and could be

accompanied by mucosal lesions and

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fever. This study also states that

paracetamol can cause flushing,

hypotension, tachycardia, and is

potentially linked to the development of

childhood asthma if mother’s are

exposed during pregnancy. As well,

acute liver failure is considered a major

adverse effect with the use of

paracetamol, being seen in both adults

and children.

Vyas et al. (2014) This randomized comparative study did

see vomiting and abdominal pain as

adverse effects of taking paracetamol,

although these reactions were not seen

in all patients.

The Mayo Foundation for Medical Education and Research (2015)

Outlines that paracetamol can cause rare

side effects like blood in stools,

haematuria or cloudy urine, sharp lower

back pain, pinpoint red spots, rash, hives,

ulcers or sores, decrease in urine output,

tiredness, and yellow of the skin and

eyes. Also if dosing is not followed as

per instructions over-dose can occur.

4) Beta-blocker: Carvedilol

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Class: Beta-adrenergic blocking agent, alpha1, nonselective beta-blocker (MIMS

Australia 2015)

Indications: Carvedilol is used for hypertension (MIMS Australia 2015) and

congestive heart failure (mild to severe) (Bryant & Knights 2015, p.247).

Mechanism of Action: Carvedilol has haemodynamic effects on β₁, β₂ and α-

adrenoceptors, and blocks their activation. A study by Jing Duan et al. (2010, p.996)

outlines that carvedilol is a β-adrenorector antagonist, but has other non-beta-

blocking actions like causing vasodilation, antioxidant and neuroprotective actions

(Inhibition of potassium channels), reduction of mitochondrial damage, and protection

against apoptosis.

Efficacy and limitations: A randomised, controlled, double-blind study done by

Hori, Izumi & Matsuzak (2014, p.245) determined that carvedilol did have an effect

on lowering heart rate in patients with chronic heart failure, but did not have an effect

on systolic or diastolic blood pressure. A prospective, randomized, open, blinded-

end point, multi-centre study by Kim et al. (2014, p.53-57) saw that using carvedilol

reduced brachial blood pressure significantly (systolic and diastolic), decreased

central pulse pressure, saw no significant difference to cfPWV, and saw a significant

increase to triglyceride levels, while lowering HDL cholesterol levels.

Cautions/contradictions: MIMS (2015) outlines carvedilol can cause

decompensated heart failure, asthma, allergic reactions, sick sinus syndrome,

cardiogenic shock, worsening heart failure, withdrawal symptoms, and hepatic

dysfunction. Also, carvedilol should be taken with caution by patients taking CYP450

inducers and inhibitors (ex: grapefruit juice), and in people with worsening heart

failure, severe hypertension, diabetes, and hypersensitivities (MIMS 2015). Caution

should also be taken in children under age 18, pregnancy and lactation (MIMS 2015).



Hori, Izumi & Matsuzak (2014, p.245) This study outlined that a rare adverse

effect in patients with chronic heart failure

taking carvedilol were the development of

diabetes mellitus and gastrointestinal

bleeding.

Kim et al. (2014, p.54) This study saw some adverse effects like

back pain due to acute transverse

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myelitis, chronic sinusitis, and 1 case of

facial oedema, dizziness and nausea.

The Mayo Foundation for Medical Education and Research (2015)

The Mayo Clinic outlines a large list of

adverse reactions that may occur when

using carvedilol. The more commonly

seen effects are allergic reaction, chest

discomfort or tightness, dizziness,

fainting, oedema of the feet/ankles/legs,

shortness of breath, slowed heartbeat,

weight gain, tingling sensations, and

diarrhoea.

(Acharya, Wilton & Shakir 2005, p.4) A cohort study followed over 800 patients

to look specifically at the adverse

reactions when taking carvedilol. These

reactions included dyspepsia, lassitude,

depression, respiratory infections, deep

vein thrombosis, and wheezing, although

symptoms were varied and moderate.

Conclusion:

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Currently the TGA is responsible for the research, licensing, safety, monitoring, and

surveillance of pharmaceutical and complementary products on the Australian market.

Although there is a regulating body, there are many over-the-counter drugs that offer

medicinal benefits, but run the risk of adverse health effects. As outlined throughout this

report, a relatively healthy individual should weigh-out the risk-benefits in relation to taking

some of these discussed pharmaceuticals. Unfortunately, some of the drugs like Warfarin

are necessary to ensure the continued health of some individuals. Education is key and

creates patient awareness, which is very important in a pharmaceutically driven society that

is seen today.

References:

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Acharya, N, Wilton, L & Shakir, S 2005, 'Observational cohort study to monitor the use and

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