Flashcards in topic 5 Deck (18):
What are two factors that affect drug effects even before a patient takes the medication?
compliance and medication errors (physician, pharmacist, nurse, patient).
How does age affect drug effects? What are some specific factors it affects and how?
Total body water % of body weight decreases with age
Fraction of lipophillic drug in fatty tissue increases with age
LIver metabolism of drug capability increases then decreases with age
Renal drug elimination capability increases then decreases with age
What are the differences between infants, children, and elderly in absortion, distribution, biotransformation, and excretion
Absorption-not many differences
Distribution-infants (incomplete BBB, higher Vd for water soluble drugs); children-none; elderly-higher Vd for fat soluble drugs
Biotransformation-infants (lower rate of oxidative rxns and gluconurate conjugation), children-biotrans. rate sometimes higher than for adults, elderly-reduced oxidative metabolism
Excretion-infants and elderly (reduced capacity to excrete drugs, children-no change
How does sex factor into drug effect
Females usually have more adipose tissue and less water percentage which affects distribution
How does weight factor into drug effects
Especially when the Therap. index is small, weight plays a big factor.
It can get especially complicated with very lean and very obese patients due to % of fats and water in body.
Body surface area is sometimes more indicative than just weight.
What is tolerance, which body system does it affect the most?
Tolerance is decreased responsiveness to a drug after prior exposure or repeated exposure to the same or a similar drug
Drugs that affect the nervous system are especially suspectible.
What are the 3 general types of tolerance and how do they work?
Tachyphylaxis- Acute, happens rapidly and usually when a drug is given at repeated short intervals
Pharmacokinetic tolerance-more chronic, when a drug reduces its own absorption, transfer across barrier, or increases elimination (induction, inhibition)
Pharmacodynamic or cellular tolerance-reduction in the normal activity of the receptor or coupling factors
what are the two types of desensitivation and how do they work?
Homologous-only drugs at the same receptor are desensitized, Drugs with same effect at different effector are not affected. Examples include covalent modification of receptor, destruction of receptor, internalization of receptor
Heterologous-Drugs from different receptors but with same affect are both desensitized (same pathway).
What are some other terms to describe desensitization?
Inactivation-loss of ability of a receptor to respond to stimulation by a drug
refractory-time is need before a receptor can again accept a ligand and produce an effect
Down-regulation-repeated drug/receptor interactions lead to the removal of the receptor from the membrane.
What is the placebo effect?
When the effects of a drug are temporally correlated with its administration but can't be attributed to its chemical properties.
What are 3 drugs with a genetic factor? What are the results, the mode of inheritance and the genetic basis?
Succinycholine-skeletal muscle relaxant for surgery, a defective plasma cholinesterase makes it so succinycholine can't be broken down as quickly, leading to persistent apnea and paralysis
Isoniazid-anti tuberculant. A deficient acetyltransferase (half of the U.S. are slow acetylators) leads to too much INH which inhibits hepatic-mixed function oxidases (P450) which inhibits the biotransformation of phenytoin (anti epileptic) making it toxic. Peripheral neuropathy is also more common among slow acetylators, but that can be treated.
Primaquine (antimalarial), sulfonamide, probenecid, chloramphenicol (all oxidative drugs)-deficiency in Glucose 6 phosphate dehydrogenase (G6PD) in erythrocytes can lead to hemolysis of RBCs especially when taking these oxidative drugs. Common among sephardic jews, african americans.
what are two examples of drug drug interactions that occur during absportion and their effects?
Tetracycline-The presence of Al3+, Ca, Mg, Bi, Fe2+, and Zn2+ ions will cause chelation of the tetracyclines, which makes them poorly soluble and decreeased absorption.
Digitalis-Anticholinergics reduce gut motility and thus cause reduced absportion.
What's an example of a drug drug interaction during protein binding.
Warfarin-when phenybutazone is added, warfarin no longer binds as much to albumin which increases its effects.
What are 3 examples of drug drug interactions at receptor sites b/w drugs with similar effects
2 anticholinergics leads to enhanced anticholinergic affects (heat stroke in hot and humid ocnditions, toxic psychosis, paralyzed bladder/gut)
2 CNS depressants lead to enhanced CNS depression (drowsiness)
2 neuromuscular blockers lead to enhanced neuromuscular blockade (prolonged apnea).
What is one example of drug drug interactions at receptor site with opposing effects?
Beta-adrenoreceptor stimulating bronchodilator taken with non-selective beta-2-adrenoreceptor blocker leads to bronchodilator effects being antagonized.
What are two kinds of drug drug interactions dealing with drug metabolism with examples?
Anticoagulants taken with barbituates leads to lessened anticoagulants effects.
Contraceptives taken with barbituates, phenytoin, or rifampicin leads to reduced contraceptive reliability
Enzyme inhibition-phenytoin taken with chloramphenicol or disulfiram leads to increased serum phenytoin levels and possible development of intoxification.
What are two ways in which drug interactions can lead to altered renal clearance
Changes in urinary pH-ion trapping in the kidney, acidic drugs less likely to be excreted in acidic urine and so on.
Competition for active tubular secretion