Renylee: @Obinoscopy

Methotrexate is a folic acid antagonist that
prevents development of the embryo. It may also
affect the attachment of the embryo to the uterine
wall.

JellyBean190:
I think I'd readily agree with previous speakers above who question the safety of quinine in the first trimester (sorry, I'm still new to this highlighting and commenting biz) because I've had my own setbacks with it; then add that to d fact that some people even use it as an abortifacient.
I remember in one CME we had, there was this heated debate about it. Some doctors, especially the older consultants were suggesting that pv bleeding in pregnancy after quinine administration was probably due to d malaria itself and not d drug. Others pointed out that it only happened soon after quinine was administered and almost always with quinine alone.
I'd like to suggest that when we quote the National Guidelines, we should state the year because these documents are revised from time to time.
This topic is ever relevant because contrary to my medical school teachings about quinine being the safest drug for malaria treatment in pregnancy, some platforms now state explicitly that quinine should be avoided in the first trimester eg Medscape and a few others I can't recall now. But we know medicine evolves so we should be able to adjust when sufficient evidence is presented. Thanks.
Contributions welcomed please.

Quatermaine:

Winzor78:
What's teratogenesis?. Sorry 4 taking u guyz back!

Teratogenesis is development of cogenital abnormalities in humans at the Organogenesis stage. e.g cases like a child with the hand protuding from the stomach rather than where it ought to be.

Mr Obino help out oh. na Pre-Med ai be. I haven't even started. grin

winzor try wikipedia

dexterinc2003:

Renylee:
Are diuretics first line drugs for hypertension or just adjuncts?

it depends on the patient you r dealing with...in most general hospitals you find these days,we combine this classes.Generally diuretics are added as an adjunct.for example thiazide diuretics have been found to be more effective in blacks ,so it is added as an adjunct. so if u are dealing with a patient with a lot of co morbidities like diabetes,asthma ,stroke you av to analyze the side effects before prescribing,you dont want to give a diabetic a beta blocker or a drug that will cause hyperglycaemia(thiazide diuretic),also you dont want to give a beta blocker to as asthmatic....hope that helped

dexterinc2003:

Liverpoolfc:
can you pls explain how it causes hyperglycemia?

thiazide diuretics also causes hypokalaemia,hypokalaemia inhibits insulin,without insulin ther is hyperglyceamia.

adeola_drg:

Winzor78:
What's teratogenesis?. Sorry 4 taking u guyz back!

Got this from a certain pharmacology app I found on GooglePlay.. TrcPharmacology. Try it!

Congenital malformations can be defined as nonreversible functional or morphological defects present at birth. Of course, not all malformations can be attributed to drug use during gestation. Environmental factors alone, such as maternal disease or infection, chemicals and drugs, account for between 5% and 9% of the malformations. Only a small portion of these are due to drugs acting as teratogens. However, this is still a very significant number to the one or two families out of every 1,000 with a child born with a major congenital malformation.
The risk of teratogenicity must be described in relative terms, since modern science has no way to predict with any real accuracy which drug exposures will result in teratogenesis during a particular pregnancy. Available data allow only the description of a relative risk to a patient population. Although there are data describing the effects of many drugs on animal development, these effects are not uniformly applicable to human pregnancies.
Check also drugs during pregnancy.

Factors that determine the effects of teratogens include the following:
Dose reaching fetus
Most drugs cross the placenta by simple diffusion. Many actually reach 50%–100% of the concentration in fetal blood as that in maternal blood. The rate at which drug transfer takes place depends on the drug characteristics, the blood flow of the uterus, and maternal kinetics.
Point in development when drug exposure occurs
During the period from conception to 2 weeks, there is a relative resistance to drug effects. Usually exposure during this time produces an “all or none” effect. The remainder of the first trimester (week 4 - 10) is the most critical time for organ malformation. Unfortunately, this is also a time when many women are unaware of their pregnancy. Drugs that reach the embryo at this point may produce abortion, no effect at all, an anatomic defect (teratogenesis), or a subtle metabolic or functional defect that may not be detected until later in life. During the second and third trimester, known as fetogenesis, drugs are less likely to be associated with major malformations, but they may influence neurologic development, growth, physiologic and biochemical functioning, mental development, and reproduction.
Duration of exposure
Environmental factors
Susceptibility (resistance) of the fetus

The most common effects of teratogens on the fetus are:
Spontaneous abortion
Defects in development
Malformations (major or minor)
Intrauterine growth retardation
Mental retardation
Carcinogenesis
Mutagenesis (causing genetic mutation)
Some drugs, such as warfarin, phenytoin, and alcohol, cause a group of effects specific for exposure to that agent. These recognizable patterns of congenital anomalies are named after the drug known to cause them, thus the terms “fetal alcohol syndrome,” “fetal warfarin syndrome” or “fetal hydantoin syndrome.”
Examples:
Fetal alcohol syndrome is defined as the presence of several of the following: prenatal and postnatal growth retardation, mental retardation, poor coordination, hypotonia, hyperactivity, microcephaly, short upturned nose, micrognathia or retrognathia in infancy, short palpebral fissures, hypoplastic philtrum, thinned upper lips, and, less frequently, anomalies of the eyes, mouth, heart, kidneys, gonads, skin, muscle, and joints. This group of defects is seen in mothers with high-dose alcohol intake during their pregnancies.
Fetal warfarin syndrome is seen in up to 25% of fetuses with first-trimester exposure to coumarins. This distinct pattern of anomalies includes nasal hypoplasia, depressed bridge of nose, and bone stippling on x-ray. A distinctly different pattern is seen with second- and third-trimester exposure to coumarins, featuring optic atrophy, cataracts, mental retardation, microcephaly, microphthalmia, deafness, growth retardation, scoliosis, seizures and hemorrhage.

Maternal health is critical in maintaining the viability and function of both mother and fetus during pregnancy. It is therefore important toj treat the mother for illnesses, that may complicate the pregnancy through maternal illness. Although, for every drug the risks and benefits should be weighed out. Ideally, a patient should seek information about drugs and their potential effect on fetal development before becoming pregnant. Women of childbearing age taking known teratogenic drugs for therapeutic indications should be advised to adhere strictly to effective contraception. A pregnant woman may believe that no drugs of any kind should be taken during pregnancy, or she may have other incorrect information or beliefs that lead to noncompliance. Inadequate treatment of the maternal illness may further endanger the mother and fetus. On the other hand, she may believe nonprescription drugs do not pose any hazard to her child since they are so readily available for self-medication.
What are considerations in the following situations?
Chronic maternal diseases such as diabetes, hypertension, epilepsy, and asthma must continue to be treated throughout pregnancy to protect the mother’s health as well as the integrity of the child’s development. Chronic diseases may be more safely managed during pregnancy with alternative drugs used for the condition that have not been implicated in teratogenesis.
Acute maternal diseases such as infections must also be effectively managed. Choice of anti-infectives may be made balancing efficacy with risk. For fever or pain, NSAIDs are not recommended during the third trimester; therefore paracetamol is a good alternative

Abdulsalax:

adeola_drg:

What is the best drug used to treat a patient with hypertension and diabetes?

the first line treatment for hypertension according to international convention is diuretic followed by beta blockers but it has been found that in africa using both together or diuretic with methyldopa works better

dexterinc2003: @Abdulsalax

the real question is are you asking because you honestly want to know,or because you want 2 argue..if its the former,then i will indulge you,a lot of textbooks will tell u different things,but im taking you one step ahead,im talking practical medicine....putting into consideration the age,sex,race,comorbidities ,the stage of the hypertension,and your target blood pressure,then you should know that the management of hypertension is not rocket science.you weigh your options,look at all the following i av listed above,then you will know which combination best suits your patient.

ps;if u happen to be a patient with malignant hypertension and the doctor hands you a diuretic alone as first line,pls run for your life.

1k001:
Hi all, stumbled on the thread. Great idea, will be contributing as much as i can

Regarding the ongoing discussion on HTN

An acceptable algorithm as prescribed by the NICE that many including myself follow is:

If patient white or under 55 commence them on ACE-I/ ARB

If black or over 55 recommendation is to start on a CCB

If further treatment is needed, add on CCB to ACE-I and vice versa depending on above

Further step up drug recommended is thiazide like diuretic

Then consider other diuretic, alpha or beta blocker if resistant

Note that this is of course only a guideline and is not a substitute for clinical judgement.

For example i've often used as firstline an ACE-I on black diabetics due to it's renal and cardioprotective effects

adeola_drg: @dexterinc2003

Not at all. I'm in the process of learning so I decided to post on an issue I came across. A particular class of hypertensive drugs is used for or preferred for treatment of HTN with diabetes mellitus. I only expected u mentioned the class I read about or explain if u think I'm saying crap, I'd be grateful.

1k001:

dexterinc2003:
more on cvs pharmacology trivia...

HEART FAILURE; heart failure is the inability of the heart to pump enough blood to meet the body's metabolic requirements.

heart failure drugs can be classified using the following mnemonic...ABCD

A; Angiotensin converting enzyme inhibitors and angiotensin receptor blockers eg captopril/losartan
B; beta blockers eg labetalol
C; Calcium channel blockers eg nifedipine
D;Diuretics eg frusemide,hydrochlorothiazide

I'll go a step further and give brief comments on the above for those interested in further reading

ACE - I - Landmark CONSENSUS trial showed improved mortality compared to placebo. Known to attenuate cardiac remodelling among other cardioprotective effects

Beta blockers - It used to be heresy to give this in heart failure but thanks to the MERIT-HF and CIBIS trials we now know they improve mortality. Among other tihings, it reduces sympathetic activation of the heart which has been implicated in heart failure morbidity and mortality

CCB - there's no real evidence for a mortality benefit i can think of off the top of my head. Useful however in treatment of HTN and angina

Diuretic - The rational is simple really. fluid retention in heart failure means excess fluid, diuretics get rid of excess fluid. Loop diuretics are drug of choice. In the setting however of acute poulmonary decompensation might be useful to add on a thiazide

A drug that was missed is SPIRONOLACTONE. The RALES trial showed a mortality benefit making it an important drug in the heart failure cocktail. Reason being the RAAS cascade is stimulated excessively in heart failure. spironolactone being an aldosterone antagonist mitigates this

Worthy of mention is the great foxglove plant derivative discovered by wiliam withering from a herbalist who used it to treat 'dropsy' ( heart failure). Digitalis/ digoxin (cardiac glycosides) make people feel good but confers no mortality benefit. It is really only indicated for rate control in atrial fibrillation, a discussion for another time

Abdulsalax: @dexterinc2003

i am also a student and i am more than willing to learn. Based on the criteria you set above, you didn't mention any particular class of the drug best suited. Will like to know that pls!! Also on the diabetes treatment.

1k001:

Renylee:
Please, can somebody explain the mechanism by which diuretics cause hypoglycaemia?

Looking at the literature it appears most anti-hypertensives cause hyperglycaemia except for alpha blockers.
The one that gets most 'bad press' for this is thiazides. I'm not sure if it's universally accepted but it has been postulated that the hyperglycaemic effect of thiazides is related to it's effect on potassium

Thiazides reduce extracellular potassium causing a hypokalaemia. This translates into decreased intracellular K via the ATP dependent K channel on the beta cell surface. This makes the rate of depolarization slower, which means slower calcium influx and thus slower insulin release.

To support this hypothesis several papers have demonstrated that the level of hyperglycaemia is proportional to K levels in thiazide users and normalization of their K lowers serum glucose. Furthermore in users who have an abnormal FBG, 2 hr post prandial glucose levels are often not raised.

Altogether i don't think that it precludes thiazides from use as the ALLHAT study of > 30,000 patients showed it was superior in BP control and CV disease prevention compared to ACE-I and CCB. If the hyperglycaemia was significant one would think it would show up in this study as detrimental

dexterinc2003:

adeola_drg:

What is the best drug used to treat a patient with hypertension and diabetes?

for hypertension with diabetes ,i would go for an angiotensin converting enyme inhibitor(captopril) or angiotensin receptor blocker(losartan)if the person is coughing with captopril....plus a calcium channel blocker(nifedipine)


reasons....ACEIs or ARBs are renoprotective,which is needed in diabetic nephropathy
thiazide diuretics is excluded cos of the hyperglycaemia side effect(bad for diabetes)
CCB can also help protect d libido of young males.

aieromon: @dexterinc2003

Quick question,why always the reference to captopril? In Nigeria,lisinopril is the most common ACEI.

dexterinc2003: @aieromon

just a prototype,.....we r advocating for knowledge,not self medication
and yes lisinopril is d commonest.

adeola_drg:

dexterinc2003:
for hypertension with diabetes ,i would go for an angiotensin converting enyme inhibitor(captopril) or angiotensin receptor blocker(losartan)if the person is coughing with captopril....plus a calcium channel blocker(nifedipine)

reasons....ACEIs or ARBs are renoprotective,which is needed in diabetic nephropathy
thiazide diuretics is excluded cos of the hyperglycaemia side effect(bad for diabetes)
CCB can also help protect d libido of young males.

I'm impressed. Buh ARBs are first line in this kind of condition, next is ACE.. Thank you, I'm here to stay.

aieromon:

dexterinc2003:
CCB can also help protect d libido of young males.

Based on my interaction with cardiologists, I'm not so sure about this.

dexterinc2003: @aieromon

lol....i was about to tell you 2 look at what i wrote well....yhanks,typo corrected..

dexterinc2003:
cardiorespiratory trivia

Acute pulmonary edema drugz mnemonic.......LMNOP

L; Lasix(frusemide)
M;Morpheine
N;Nitrates
0; Oxygen
P;Prednisolone

1k001:

Renylee:
Please, can somebody explain the mechanism by which diuretics cause hypoglycaemia?

Looking at the literature it appears most anti-hypertensives cause hyperglycaemia except for alpha blockers.
The one that gets most 'bad press' for this is thiazides. I'm not sure if it's universally accepted but it has been postulated that the hyperglycaemic effect of thiazides is related to it's effect on potassium

Thiazides reduce extracellular potassium causing a hypokalaemia. This translates into decreased intracellular K via the ATP dependent K channel on the beta cell surface. This makes the rate of depolarization slower, which means slower calcium influx and thus slower insulin release.

To support this hypothesis several papers have demonstrated that the level of hyperglycaemia is proportional to K levels in thiazide users and normalization of their K lowers serum glucose. Furthermore in users who have an abnormal FBG, 2 hr post prandial glucose levels are often not raised.

Altogether i don't think that it precludes thiazides from use as the ALLHAT study of > 30,000 patients showed it was superior in BP control and CV disease prevention compared to ACE-I and CCB. If the hyperglycaemia was significant one would think it would show up in this study as detrimental

1k001:

adeola_drg:

I'm impressed. Buh ARBs are first line in this kind of condition, next is ACE.. Thank you, I'm here to stay.

I think that you will find that the literature is more in favour of ACE-I than ARB's. The latter being used mostly when there is ACE-I intolerance. I've heard many a cardiologist repeat the aphorism: ACE-I is the drug you give to your mother and ARB is the drug you give to your mother in law

1k001:

dexterinc2003:
cardiorespiratory trivia

Acute pulmonary edema drugz mnemonic.......LMNOP

L; Lasix(frusemide)
M;Morpheine
N;Nitrates
0; Oxygen
P;Prednisolone

Seeing as we're discussing clinical pharmacology i'll comment on the above trivia:

With acute pulmonary edema what you need is diuresis, diuresis and more diuresis

frusemide (usually intravenously) is drug of choice, a thiazide like diuretic such as metalozone may be added on for a synergistic effect

Morphine helps the dyspnoea via venodilation and also helps reduce the associated anxiety. note however it may drop the BP and give you less room to play with in achieving your 1st aim of diuresis, diuresis, diuresis. I wouldn't routinely use it, some even say to avoid it entirely.

Simlarly nitrates usually drops the BP and constrains diuresis although it is useful in symptomatic relief. I would use it infrequently

Oxygen helps only when the patient is hypoxic. Otherwise it may be deleterious; free radical generation and all that jazz.

Regarding prednisone, unless one feels the edema is as a result of an inflammatory process it would not be advisable to give it. In any case its use in noncardiogenic pulmonary edema is still equivocal at best so I would avoid it altogether

...Still haven't been inducted. Won't stop me though smiley happen to be somewhat between jobs at the moment with a bit of time on my hands

Arsenate:

1k001:

I think that you will find that the literature is more in favour of ACE-I than ARB's. The latter being used mostly when there is ACE-I intolerance. I've heard many a cardiologist repeat the aphorism: ACE-I is the drug you give to your mother and ARB is the drug you give to your mother in law

interesting. the cardiologists are implying that ACEIs are superior to the ARBs? how so? from what I understand ARBs are more potent antihypertensives since RAS isn't the only pathway through which angiotensin is produced. furthermore, the ARBs are devoid of adverse effects associated with bradkynin accumulation e.g cough.

Emzybrown:
Ok let me make my contribution.
Pharmacology is the scientific study of drugs/selective biological activity of chemical substances in living material and its effect on the body which may be desirable or undesirable. Pharmacological terms include pharmacotherapeutics, pharmacogenetics, pharmacodynamic, pharmacokinetics.
Pls note: My lecture is not meant for advance pharmacologist but targeted to the novice in our midst, who intend to grab some knowledge.
Pharmacotherapeutics: is the use of drugs in the treatment of diseases. However drugs are not only use to manage diseases.we can use drugs for prophylasis, to correct body functions, make diagnosis, eliminate symptoms, support physiological functions,substitute body secretions.
Assignment: read exhaustively about drugs,sources.

Pharmacokinetics: refers to the process concerned with the distribution of drugs in the body as in their absorption, excreation and metabolism. In simple term it means what our body does to drugs.
Drugs may be solid in form of capsules, tablets, pills, or volatile liquids, solution, aerosol, gas, crystalline suspension. Route of adminstration can be topical/local,systemic. Example of routes are oral, intra venous, intra muscular, sub cutaneous, sublingual, intra nasal,intra womanly e.t.c
Bioavailability of drugs is the effectiveness of various method of adminstration in delivering the drug to its various site of action.
Drug metabolism takes place at the liver cells, kidney,plasma,. The liver is the major organ for drug metabolism,detoxification. Biotransformation is the ability of living organisms to modify the chemical structure of drugs through an enzyme catalysed process.
Assignment: read various ways by which drugs can be metabolized in living organisms.

Pharmacodynamics: may be defined as the study of the actions and effects of drugs on the body at organ,tissue,cellular and subcellular levels. It deals with the site, mode, and mechanism of drugs action.
Pharmacogenetics is the study of genetical markup of an individual as it affects or alters drug action. It deals mainly why drug action varies among individuals.
Finally i would like to appreciate my Chemical pathology lecturer Dr D.C Nwosu, department of medical laboratory science, imo State University Owerri for his pharmacology and toxicology lectures which i enjoy very well.

Sorry for any errors, i typed with my java phone.

1k001:

Arsenate:
interesting. the cardiologists are implying that ACEIs are superior to the ARBs? how so? from what I understand ARBs are more potent antihypertensives since RAS isn't the only pathway through which angiotensin is produced. furthermore, the ARBs are devoid of adverse effects associated with bradkynin accumulation e.g cough.

Bear with me as I answer this in a simple manner to aid those who haven’t much pharmacology experience.

The reasons for prescribing drugs are numerous but ultimately boil down to morbidity (disease) and mortality (death). Drugs aim to prolong life and improve its quality or at least reduce its rate of decline. The measure of a drug efficacy is thus ultimately related to its effect on morbidity and mortality.

Regarding hypertension (HTN), studies show that both Ace inhibitors (ACE-I) and angiotensin receptor blockers (ARB’s) are largely equally effective in treating it. That means they have equal effect on morbidity.

On the other more important measure of mortality there’s only one winner; ACE-I
A recent metanalysis (a large pooling of results from different trials- the gold standard of evidence base) by Ferrari et al in June 2013 http://www.ncbi.nlm.nih.gov/pubmed/23750680 showed

a 10% reduction in relative risk for all-cause mortality! and

a trend toward a 12% reduction in cardiovascular mortality!

ARB’s had no effect whatsoever on mortality. In fact in some studies it actually increased the risk for myocardial infarction (heart attack).

This seems a bit counter intuitive that while they both act on a similar cascade and equally reduce BP, one reduces death while the other increases death (putting it bluntly). The answer lies in the pharmacology.

ACE-I prevents Angiotensin 2 from being made, Angiotensin 2, a vasoconstrictor is basically not good for you so blocking it’s action is good. ACE-I has an added advantage of producing excess bradykinin which does get a bad rep for cough in some people but has been shown to be beneficial to the CVS (cardiovascular system)

ARBs on the other hand block the angiotensin 2 receptor, thus blocking the vasoconstrictor effect of Angiotensin 2. It however blocks only one subtype, the AT1 receptor. Other receptors AT2, 3 and 4 are still stimulated by excessive Angiotensin 2. This isn’t great seeing as AT2 is known to be involved in inflammation and cell death. This gives rise to the mixed effect of ARBs

I hope my relatively short explanation suffices and has encouraged you to give ACE-I as first line and only use ARBs if there is intolerance. Happy to answer any further questions.

alstacs:

Obinoscopy:
Quinine is very safe in pregnancy. Its the only drug that I know to have an established safety profile during the first trimester. However its cinchonic side-effects on the mother is the main reason why most patients don't like taking it. Most prefer the Artemisinin Combination Therapy Regimen (its still okay to take this in the first trimester if its benefit outweighs its risk) or even Chloroquine (also safe during 1st trimester). I've never gotten a complaint regarding the incidence of womanly Bleeding during pregnancy due to Quinine usage from either the doctors, nurses or patients in the hospital I worked in. However, I think its left for other clinicians to give us their own experience in this matter.

Regards.

Quinine was actually classified as unsafe in pregnancy in the past and the WHO and National guidelines on malaria treatment that proposed quinine as the drug of choice in early pregnancy was challenged by many. it is however important to note the drug had been reclassified.
Safety in studies is one thing, on the other hand however is clinical tolerability and acceptability to the patient. With the advent of patient centred care, consideration of the latter is very important. therefore, quinine is pharmacologically safe but not tolerable or acceptable to most patients.
Talking about our personal experiences to establish side effects and facts may not be the best as we may be wrong in our observations. please refer to evidence based medicine and our personal experiences may not carry any weight at all.

by the way, this is a nice thread if the delinquents don't invade as usual. I wish to observe from the background.....so no induction for me.

Liverpoolfc:
The autonomic nervous system Is ''automatic'' devoid of voluntary control. It control the activities of the viscerals such as the heart, kidney, blood vessels etc. It is also known as the vegetative system. The autonomic nervous system is subdivided into two namely the sympathetic and parasympathetic. It should homever be noted that some text books include enteric as the third division of ANS.
The sympathetic division uses norepinephrine as its neurotransmitter while the parasympathetic divison uses acetylcholine as its neurotransmitter.
To understand their various activities, ask yourself this question, '' what will happen now if I hear a gun shot in the next room? Guy 1) your heartrate will increase, ur bp will be high, you pupil will dilate to see better, your joystick will relax even if it was ready for action, the bronchioles will dilate etc. All the above named activities are sympathetic and exogenous agent that helps bring about /facilitate sypathetic activities are said to be sympathetomimetic agent.
The parasympathetic nervous system often known as Rest and Digest system is set into play when a guy sees a chick and he is in happy mood. E.g his joystick will rise(Attention) his pupil will constrict so he will see less,all git activities will increase, heart rate will decrease etc exogenous agent that help to facilitate parasympathetic nervous system are know as parasympathomimetic agent.
Anatomically, the sympathetic nervous system is said to be thoraco lumber in origin while that of parasympathec nervous system is said to be craniosacral in origin.
This is not a presentation yet just a brief discussion on ANS, if there is lite in my crib tonight, I will present the pharmacology part.

1k001:
Oral anticoagulants

Warfarin (coumadin) VKA

Indications

Prophylaxis of systemic embolism in patients with rheumatic heart disease and atrial fibrillation.

• Prophylaxis after insertion of prosthetic heart valves.

• Prophylaxis of venous thrombosis and pulmonary embolism and for use in the treatment of these

conditions to prevent their extension.

Pharmacology

Vitamin K antagonists. It acts by inhibiting the formation of active vitamin K dependent clotting

factors II, VII, IX and X.

Interactions

Other anticoagulants/ antiplatelets – increased bleeding risk

Metabolized by cytochrome P450 enzymes – 1A2, 3A4, 2C9 thus medications that induce

(phenytoin, rifampicin) or inhibit (cimetidine, ketoconazole) these enzymes will interact.

Broad spectrum antibiotics that reduce vit K producing gut flora e.g clarithromycin

Others such as alcohol, herbal preparations, grapefruit juice

Notes

Has narrow therapeutic window so needs regular monitoring with INR

Is pro-thrombotic when first initiated as it inhibits protein C & S before the clotting

factors. May need alternative anticoagulant until therapeutic INR reached

Clinical risk scores such as ‘CHADSVASC’ in a.fib and ‘HASBLED’ are useful in

deciding risk and benefit of initiating it

May be reversed by ingestion of Vitamin K

NNT – 1 in 25 to prevent stroke

1 in 42 to prevent death from any cause


Dabigatran – Direct thrombin inhibitor

Indication

Initially was only for thromboprophylaxis in hip and knee replacement but has now

been extended to include stroke and systemic embolism prevention in non valvular atrial fibrillation (AF) thanks to the RE-LY study

Pharmacology

Is a direct thrombin inhibitor. Thrombin enables conversion of fibrinogen to fibrin

in coagulation cascade, its inhibition results in reduced thrombus formation. Also

inhibits thrombin induced platelet aggregation

Interactions

Other antiplatelets/ anticoagulants – increased bleeding risk

is a substrate for the P glycoprotein transporter so may interact with inhibitors (Amiodarone,

verapamil, clarithromycin or inducers (Rifampicin, carbamazepine, phenytoin

Increased bleeding risk with SSRI and SNRI (Pgp substrates)

Notes

Dose is usually 220mg in 2 daily divided doses i.e 110mg bd

Reduced dosing in renal impairment and elderly patients

No need for routine monitoring,

APTT may help estimate extent of anticoagulation but not totally reliable.

If any HB drop during treatment, bleeding source should be identified

No reversal agent is available although I hear research on a specific antibody is at an advanced

stage. It will no doubt be bloody expensive!


Rivaroxaban – Direct Xa inhibitor

Indication: similar to Dabigatran was initially for Prevention of (VTE) in adult patients

undergoing elective hip or knee replacement surgery. License has since been extended to use in non valvular AF. See ROCKET-AF trial

Mode of action – Is a direct factor Xa inhibitor, it thus interrupts the intrinsic and extrinsic

pathway of the coagulation cascade

Interactions

Increased bleeding risk with other anticoagulants/ antiplatelets

Metabolized by CYP 3A4 and PGP. May interact with inhibitors and inducers of both

Notes

Use with caution in renal impairment

No specific antidote

Similar drug apixiban has shown less bleeding risk compared with other oral anticoagulants in

recent studies

Short summary, by no means exhaustive. Comments or questions welcome

Obinoscopy:
Guys find below a Case Study on Clinical Pharmacology culled from Katzung:

A teenage boy is seen at the office of a dental surgeon for extraction of an impacted wisdom tooth. He is so nervous
that the dentist decides to administer a sedative to calm the boy. After intravenous administration of the sedative (promethazine), the boy relaxes and the extraction is accomplished with no complications. However, when the boy stands up from the dental chair, he turns very pale and faints.

Lying on the floor, he rapidly regains consciousness, but has a rapid heart rate of 120 bpm and a blood pressure of only 110/70 mm Hg. When he sits up, his heart rate increases to 140 bpm, his pressure drops to 80/40 mm Hg, and he complains of faintness. He is helped to a couch in the reception area, where he rests for 30 minutes. At the end of this time the boy is able to sit up without symptoms and, after an additional
15 minutes, is able to stand without difficulty. What autonomic effects might promethazine have that would explain the patient’s signs and symptoms? Why did his heart rate increase when his blood pressure dropped?

Liverpoolfc: @Obinoscopy

promethazine is an antihistamine with also anticholinegic activities. Inhibition of the neurotransmitter acetylcholine inhibits parasympathetic activities so, sympathetic activities are exacerbated. That's all.

Obinoscopy: @Liverpoolfc

Nice one! You too much smiley.

However you haven't given the answer to the second question: "Why did his heart rate increase when his blood pressure dropped?"