Pharmacokinetics and Pharmacodynamics Flashcards
Which form of drugs (ionized or non ionized) can cross cells membranes
Non-ionized
In order to excrete an acidic drug in the urine in the case of an overdose, which substance can be used as a treatment?
Sodium bicarb (NaHCO3)
In order to excrete an basic drug in the urine in the case of an overdose, which substance can be used as a treatment?
Ammonium chloride (NH4Cl)
Equation to calculate volume of distribution
(Vd)= Dose/Conc
A drug that binds tightly with tissues will have what kind of Vd
High Vd
Drugs that exhibit more protein plasma binding are more likely to have drug interactions by what mechanism?
Other drugs will try to displace it from the binding protein
Eg. of a drug with a low Vd
Warfarin
Eg. of a drug that competes with warfarin for plasma protein binding
What can result from this?
Sulphonylureas
Can lead to bleeding toxicity
Eg. of a class of drugs that competes with bilirubin in neonates for plasma protein binding
What can result from this?
Sulfonamides
Can lead to kernicterus (brain damage)
A consequence of hypoalbuminemia as it relates to drug levels in plasma.
What can cause hypoalbuminemia?
increased free drug level (possible toxcity)
hypoalbuminemia may be caused by (Burns, hepatic & renal disease)
A consequence of hyperalbuminemia as it relates to drug levels in plasma.
What can cause hyperalbuminemia?
Decreased free drug level
hyperalbuminemia may be caused by (dehydration)
What kind of drugs are able to cross the BBB
Only lipid soluble, non-ionized drugs
What is the mechanism of drug redistribution
drugs distribute first to organs with high blood flow then ‘redistribute’ to other tissues such as muscle and fat
Equation for calculating loading dose
Loading dose = (Vd) (Css)/F
What is meant by biotransformation
Process to increase water solubility, to inactivate the drug, achieved by converting the drug into a more excretable form
What are the 2 phases of biotransformation, where do they occur and what is involved
Phase I- Endoplasmic reticulum (Cytochrome P 450)
Phase II- Cytosol (Conjugation)
Inducers of cytochrome P450
Carbamazepine, phenobarbitone, phenytoin
Rifampin, chronic alcohol, glucocorticoids, St.John’s wort, Nevirapine, Griseofulvin
Cytochrome P450 requires which two molecules to do its job
O2 and NADPH
If a cytochrome P450 inducer is given with a drug, what is expected to be seen and why
Reduced efficacy of the drug due to increased metabolism of the drug
If a cytochrome P450 inhibitor is given with a drug, what is expected to be seen and why
Increased efficacy of the drug due to decreased metabolism of the drug (could lead to toxicity)
Inhibitors of cytochrome P450
Cimetidine
Omeprazole
Ketoconazole
Erythromycin
Which 3 processes occur during phase !! of biotransformation
- Glucuronide conjugation
- Acetylation
- Glutathione (GSH) conjugation
an eg. of a type of drug which undergoes glucuronide conjugation
oral contraceptives
Which drugs, if given to slow acetylators can cause drug induced lupus
Sulfonamides
Hydralazine
Isoniazid
Prrocainamide
Eg. of a drug which undergoes Glutathione conjugation
Acetaminophen
Equation to calculate renal clearance
Renal excretion rate/ plasma drug concentration
Most drugs exhibit which type of kinetics
First order kinetics
For drugs with first order kinetics the rate of drug elimination is proportional to ________________
the plasma drug concentration at any given time
Examples of drugs that exhibit zero order kinetics
Phenytoin,
Ethanol
Aspirin
If drug elimination mechanisms (biotransformation and excretion) become saturated, a drug can exhibit ______-order kinetics
zero order
For drugs with zero order kinetics, describe the rate of drug elimination
the rate of drug elimination is constant.
Equation to calculate Half life(t1/2)
t1/2 = 0.7/ke (or) 0.7xVd/CL
Equation to calculate Clearance (Cl)
Cl = ke x Vd
Equation to calculate Infusion rate (Ko)
Ko = Cl x Css
Equation to calculate Loading dose (LD)
LD = Vd x Css/F
Equation to calculate Maintenance dose (MD)
MD = Cl x Css x dosing interval /F
What kind of antgonist will reduce the maximal response of the agonist
Non-competitive antagonist
What kind of antagonist will cause a rightwards shift in the dose-response curve of an agonist
Both a competitive antagonist and a noncompetitive antagonist
does a left of right shift in the dose-response curve demonstrate an increase in potency
Left-shift
What are the 3 types of antagonism
- Pharmacological Antagonism
- Physiological antagonism
- Chemical antagonism
Describe a chemical antagonist
Antagonist form a complex with the agonist and reverse its action
No receptors involved
Describe a physiological antagonist
An agonist response mediated through a receptor is antagonised by an agonist acting on a different receptor
different receptors
Describe a pharmacological antagonist
An antagonist that uses the same receptor as the agonist
What kind of agonist is Buprenorphine, which drug does it interact with
A partial agonist. it interacts with morphine
How does a ceiling effect occur
Addition of the partial agonist on top of a full agonist with 100% response will displace the full against from the receptor
What is the therapeutic index
The range of doses between the minimal effective concentration and the lethal concentration
Diazepam uses which kind of receptor binding
Ligand & voltage -gated
Which receptors act via Gi signal transduction
Muscarinic 2
Alpha 2
Dopaminergc 2
MAD2
Which receptors act via Gq signal transduction
Histamine (H1) Alpha 1 V1 M1, M3
HAVe 1 MM
