Cardiovascular pharmacology: Difference between revisions
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===Drug Distribution=== | ===Drug Distribution=== | ||
====Hydrophilic Drugs=== | ====Hydrophilic Drugs==== | ||
*Muscle is high in water content. | *Muscle is high in water content. | ||
*Women have less muscle mass thereby lowering the [[volume of distribution]] of [[hydrophilic drugs]]. | *Women have less muscle mass thereby lowering the [[volume of distribution]] of [[hydrophilic drugs]]. | ||
| Line 26: | Line 26: | ||
::*[[Nadolol]] | ::*[[Nadolol]] | ||
::*[[Sotalol]] | ::*[[Sotalol]] | ||
: | :Lipophilic drugs do cross the blood brain barrier (don't give these drugs to a depressed patient): | ||
::*[[Propranolol]] | ::*[[Propranolol]] | ||
::*[[Lopressor]] or [[metoprolol]] | ::*[[Lopressor]] or [[metoprolol]] | ||
::*[[Lebatolol]] | ::*[[Lebatolol]] | ||
==Hydrophilic== | ==Hydrophilic== | ||
Revision as of 16:50, 29 September 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Scope
- 5% of questions of the boards
Pharmacokinetics
Pharmacokinetics is the effect of the body on the drug.
Potency vs Efficacy
- Potency is a meaningless measure of the effect of drug on a per mg basis. Says nothing aobut the clinical effectiveness of the drug.
- Efficacy is the clinical effectiveness of drug.
- A new more potent medicine will achieve the desired effect at a lower dose. It may not be more effective.
Drug Distribution
Hydrophilic Drugs
- Muscle is high in water content.
- Women have less muscle mass thereby lowering the volume of distribution of hydrophilic drugs.
- Older patients have less muscle mass thereby lowering the volume of distribution of hydrophilic drugs.
- Elderly women have less total body water thereby lowering the volume of distribution of hydrophilic drugs.
- Water soluble (hydrophilic) drugs are associated with a higher drug effect in patients with a lower volume of distribution like elderly women (e.g. alcohool in a woman).
- Impaired kidney function affects hydrophilic drugs as it effects the volume of distribution
- Hydrophiic drugs do not diffuse into brain.Very important in the selection of beta blockers
- Hydrophilic drugs that don't cross the blood brain barrier:
- Lipophilic drugs do cross the blood brain barrier (don't give these drugs to a depressed patient):
Hydrophilic
- In intravascular space
- Cleared by kidney
- Dont cross blood brain barrier
Atenolol, hadolol, sotalol
Intestinal Metabolism
- grapefruit juice affects intestinal system, but not liver. Intestinal cytochrome CYP3A4. (dihydropiridine CCBs,
lova, simva, cyclosporine, tacrolimus, sildenafil can be affected. May increase drug levels
Hepatic Metabolims
- beta blockers reduce hepatic blood flow, deompensated CHF affects liver blood flow
Know inhibitors\ allopurinal cipr cimet dilt eryth isoiz PPI
Inducers barb carb Know Inducers
Pharmacodynamics
Effect of drug on the body
Drug Drug Interactions
Nitrates with PD5 inhibitors
Digoxin
- Other meds
- Hypokalemia, often dont get dig toxic unless hypok, start on diuretic, then pt becoes dig toxic
- Other drugs
Teratogenicity
- Drugs cross placenta
- No drug completely safe
ACE ARB warfarin clearly bad Betablcoker can be used Alcohol, LI pheno cause fetal abn
Drugs in Lactation
Drug Overdose Mangement
Beta Blocker
=CCB
Caffeine
Cardiotoxicity
- CHF with anthracylines: related to cumulative dose, 400 t0 500 mg / m2, occurs in about a yr, progressive asx lv dysfxn.
may persist after dc of tx
- may progressive after dc
younger and old age at biggest death pathphys:cell death
minimize further exxposure chf tx worse with re-exposure
type 2 cardiotoxicity
reversibel re-challenge may be safe
St. John's Wart
- Commonly taken
- Interacts with amiodarone
Supplements that Increase Bleeding Effect
- Ginger
Adverse Drug Reactions
- 4th leading cause of death
- One third are preventable, often dont know what patient is on
- Elderly and youngerly are at risk
- Elderly:reduced muscle mass, water soluble drug concentration increased, decreased renal function, cognitive decline and mix up meds, non-compliant, co-morbidities
- Polypharmacy: OVer 5 drugs, higher risk of drug interactions. Elderly are often on ove 10 drugs
Pharmacogenomics
- Role of inheritance in variation in drug response
- Metabolism, absorption, interaction of drug with target affected by genetics
- Genetics may influence induction and inhibition (breakdown) of drugs, increase or reduce activity of drug
- Example CYP2D6: metoprolol, propafenone, tamoxifen affected. Poor metabolizers in 10% of northern europeans. Metoprolol is not broken down and easily od, codeine does not work. East africans can be ultrametabolizers: lopressor does not work, codeine toxic
- Clopidogrel
- Absorption variable
- 15% taken in is active
- 2 steps to turn it into the active drug
- CYP2c19 very important in metabolizing the drug to the active metabolite
- 2 and *3 polymorphisms are inactive, drug not activated, inadequate activity. Increase adverse events, stent thrombosis.
- Routine testing not recommedned
- If *2 or *3 allele present, then alternate therapy recommended. Pt with stent thrombosis may undergo testing and switch.
Warfarin
- Measure INR which is related to efficacy but there is still have bleeding
- Order of magnitude different doses of warfarin due to genetic difference
- Half of variability is due to geneitc variability
- CYP2C: responsible for metabolism. Therer are slow and fast metabolizers( and
- VKORc1 target of effect of warfarin
- Not clear if testing is cost-effective