Cardiovascular pharmacology: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 94: | Line 94: | ||
==Pharmacogenomics== | ==Pharmacogenomics== | ||
*Role of inheritance in variation in drug response | *Role of inheritance in variation in drug response | ||
*Metabolism, absorption, interaction of drug with target affected | *Metabolism, absorption, interaction of drug with target affected by genetics | ||
*Genetics may influence induction and inhibition, increase or reduce activity | *Genetics may influence induction and inhibition (breakdown) of drugs, increase or reduce activity of drug | ||
*Example CYP2D6: | *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. | |||
==References== | ==References== | ||
Revision as of 16:18, 29 September 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Scope
- 5% of questions of the boards
Pharmacokinetics
- Potency vs Efficacy: Potency is meaningless, effect of drug per mg. Efficacy is the clinical effectiveness of drug.
- PK is effect of the body on the drug.
- Drug distribution: muscle high in water content. Women have less muscle mass. Older patients have less muscle mass. Elderly women have less total body water. Water soluble drugs are associated with a higher drug effect (eaxample alcohool). Do not diffuse into brain. Very important in beta blockers, they are hydrophilic.
- Lipophilic drugs:Cross into CNS. Lopressor, propranolol
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.