Pharmaco-dynamics And Kinetics Flashcards
Examples of weak acids
Aspirin Ibuprofen Acetazolamide Phenobarbital Methotrexate Warfarin APIM
Aspirin and ibuprofen are what type of drugs ?
NSAIDs and used as analgesics for musculoskeletal pain
What is phenobarbital used for?
Seizures and insomnia
What is acetazolamide used for?
Used for intraocular pressure and heart failure
What is TCA used for
They are used as antidepressants
What are weak basic drugs?
- Codine
- Atropine
- cocaine
- morphine
- amphetamine
What are atropine used for?
They are used as cholinergic antagonists
What are codine and morphine used for?
They are used as analgesics for visceral pain
What substances can you use to acidify the urine to change urine ph?
NH4CL, Vitamin C, Cranberry juice
What substances can you use to alkalinize the urine to change urine ph?
- NaHCO3 (sodium bicarbonate)
Acid drug + acidifying urine subs
Acid drug + alkalinizing urine subs (and vice versa)
Explain and give examples
Like and like- nonionised and absorbed
Opposites- ionized and eliminated
What oral drug has a 100% bioavailability’s
Isosorbide mono nitrate and it’s is used for heart-related chest pain, heart failure, and esophageal spasms.
Unbound drugs cross/does not cross bio-membranes
Unbound drugs cross bio-membranes. So the fraction of the drug in the plasma that is bound is inactive and generally unavailable for systemic distribution.
Acidic drugs to ——— in plasma while the basic drug binds to ———
- plasma albumin
- alpha 1 acidic glycoprotein
Other plasma binding proteins are: lipoprotein and cortisol binding globulin
What drugs are highly bound to plasma proteins?
- OHA : Glipizide, Glimepride, Glyburide,
- NSAIDs
- sulfonamides s/e: recurrent diarrhea
- cardiac glycosides: digoxin
- Warfarin
CWONS
What are the formula for apparent volume of distribution
Total amount of drug in the body / plasma concentration of drug in the body
(Explain further)
Prodrugs and their examples
Drugs that become activated after bio-transformation
- Monoxidil
- Morphine
- Dopamine
- Prednisone
- Epinephrine
- Flurouracil
- Sulfasalazine: 5aminosalylic acid
- Zidovudine
- Mecaptopurine
- Cyclophosphaminde
- methyl dopa
- Clopidogrel
INH undergoes phase —— before phase —— during metabolism
Phase 2 before phase 1
It is first acetylated before hydrolyzed to isonicotinic acid
Alcohol could —— or —— cytochrome p450
Inhibit or induce
What are the substances or drugs that undergo non-microtonal reactions?
- Amine Oxidation e.g cathecholamins or histamine
- Alcohol dehydrogenation e.g ethanol oxidation
- Esterases e.g pravastatin metabolisid in liver
- hydrolysis e.g procaine
Explain the link between gray baby syndrome and chloramphenicol
Baby’s can’t produce enough glucoronic acid so less ionization and the accumulation of the drug.
What drugs undergo acetylation
- statins: hyperlipidemia
- Isoniazid: Tuberculosis
- procainamide: arrhythmia
- hydralazine: hypertension
- monocycline: antibiotics
PHISM
Drugs that undergo sulfation
Steroids and minoxidil
What is the purpose of glutathione conjugation for acetaminophen
It helps to convert the toxic intermediate of acetaminophen (NAPBQI) to a non - toxic form (cysteine and mercapturic acid.
Where are the cyp450 isoenzymes located?
The SER of lungs liver GIT and kidney
What are the 3 isoenzymes of CYP 450?
- CYP1A
- CYP2D6
- CYP3A4 ( common)
What is the substrate, inhibitors and inducers of CYP1A
Substrate: Theophylline
Inhibitors: Macrolides and fluoroquinolone
Inducers: aromatic hydrocarbons
What is the substrate, inducer and inhibitor of cyp2D6
Substrate: Codeine and metaprolol
Inhibitors: haloperidol and quinidine
What is the substrate, inducer and inhibitor of CYP3A4
Substrate: a wide range
Inducer: general cyp450 inducers
Inhibitor: Azoles, macrolides, acute alcohol intake, cimetidine
What are the general inducers of cyp450 enzyme?
- phenobarbital
- phenotoyin
- chronic alcoholism
- carbamazepine
- rifampin
- St. John wort
Sir Rifampin Can’t Come to our Private Property
What drug inhibits the cyp450 enzyme generally?
- azoles
- acute alcoholism
- macrolides
- cimetidine
- cranberry juice
- sodium valproate
- omeprazole
- ciprofloxacin
- allopurinol
- ritunavir
- amiodarone
- SSRI
——- is an autoinducer of CYP450 such that whatever it does affects itself.
Carbamazepine
Drugs that cause drug induced SLE
- INH
- Hydralazine
- Statins
- Procainamide
- Phenytoin
- Penicillamine
- Quinidine
NHIS PQ
What drugs increase the first pass effect?
Lidocaine: anti arrhythmic Propanol: beta blocker Verapamil: Ca blocker Aspirin: NSAIDS Testosterone Corticosteroids
(Very Poor Little CAT)
What is the most common form of elimination?
- 1st Order
What are drugs that take part in the zero order elimination process?
High doses of
- Ethanol
- phenytoin
- Salicylates (Aspirin)
PEA shaped like a O(Zero)
Clearance =
Rate of drug elimination/Plasma concentration
Or Volume of distribution (Vd) X elimination constant ( Ke)
Clearance formula in renal
Clearance = Free form x GFR
Distinguish between the half life for zero order and first order
Half life is constant for First order elimination but it is not fixed for zero order elimination.
What is the mathematical calculation of half life?
T1/2 = 0.7 x Vd/CL
CSS is dependent on T1/2
True/false
True
Difference between the mathematical steady state and clinical state
Mathematical steady state takes >7 t1/2 while clinical steady state takes >4 t1/2
What is the formula of Css?
Css= Ro/CLt
Ro: the rate of infusion (does not change the time needed to reach CSS but it changes the concentration.
CLt: total clearance
What is the mathematical calculation of Ro
Ro = Pc X CLt
Plasma concentration of the drug
So is dosing rate same as rate of infusion ?
Yes
What is the mathematical definition of maintenance dose
MD = Dosing rate X Dosing interval
Ro X DI
Or Cp X Cl X ^ /F
Pie(^) is dosing interval
What is the calculation of loading dose?
LD = Vd X Css
Note if BV is less than 1 you should double the loading dose.
From FA—> LD = Cp X Vd / F(bioavailability)
What are the characteristics of a drug receptor complex
- Antagonism
- Agonists
- Efficacy
- Potency
What are the characteristics of a graded dose-response curve
- Affinity
- potency
- Efficacy
- Antagonism
Affinity is
The ability to bind to the receptor
Closer to the y axis is more affinity
Potency is
How much drug is required to produce a response
Determined by the affinity and the two drugs must have same efficacy
Represented by the. X-value
Efficacy is
Maximum response provided by a drug
More efficient is the drug with the highest reached by the curve on y-axis
Increased y-value = increased Vmax
In The presence of Agonist partial agonist acts as ?
A nonCompetitive antagonist as the efficacy is decreased but with independent potency decrease
On the dose-response curves, competitive antagonists move agonist to where
A parallel shift to the right
It also decreases its potency
Most antagonist are?
Competitive
On the dose-response curves, non-competitive antagonists move agonist to where
A non-parallel shift to the right
It decreases both just efficiency and potency stays the same
How many are the non-competitive drugs and what are they?
SPOD
- succinylcholine CoA: nicotinic receptor
- phenoxybenzamine: alpha receptors
- organo phosphorus compound: AchE
- Diazoxide:Alpha receptors
What is pharmacological antagonism
An agonist and an antagonist competing for a single receptor and producing opposing effects
Explain physiological antagonism
An agonist and an antagonist acting on different receptors but producing different opposing effects
What is chemical antagonism?
The binding of a drug to another that the formation of complex between the effector drug and another compound reverses the action.
What is the effective dose?
The amount of drug required to produce a response in 50% of test individuals
What is a median toxic dose TD50
The amount of drug required to produce a toxic effect in 50% of test individuals
What is a median lethal dose (LD50)
The amount of drug required to kill 50% of test individuals.
What is therapeutic index
The relative safety of a drug
TI= LD/ED
OR
TI= TD/ED
Drugs with very low therapeutic index
- lithium
- Warfarin
- theophylline
- digoxin
- anti epileptic drugs
Warning these drugs are lethal
What are the phases of drug testing
1- is it safe (safety and dosage on healthy humans)
2- does it work (efficacy and effectiveness)
3- is it better (safety, side effects,effectiveness)
4- can it stay (long term pros and cons post approval surveillance )
FDA approval occurs after phase 3
What is the Micheal is menten kinetics?
It is Vi/o
=
[Vmax (S)] / [Km + (S)]
In renal and liver dx ——- dose is decreased and _______ dose is unchanged
Maintenance dose
Loading dose
Time to reach steady state depends on _____
T1/2 half life
And it is independent on dose and dosing frequency
An increase in dose of drug leads to a ____ in the concentration of Cs
Increase
More Pka mean
More basic
Less Pka mean
More acidic
Examples of competitive antagonist
Diazepam (agonist) + Flimazenil (antagonist) on GABA receptor
Examples of non competitive antagonist
Norepinephrine (agonist) + phenoxybenzamine (antagonist) on alpha receptors
Examples of partial competitive inhibitors
Morphine (full agonist) + buprenorphine (partial agonist) at opioid receptors
Example of an addictive drug effect
Aspirin and acetaminophen
Give an example of a permissive drug effect modification
Cortisol required for corticosteroids responsiveness
An example of synergistic drug effect
Clopidogrel with Aspirin
An example of potentiation drug effect modification
Carbidopa with no other therapeutic effect that to block the peripheral conversion of levodopa
An example of antagonism drug effect
Ethanol antidote for methanol poisoning
Drugs that exhibit tachyphylactic drug effect
Hydralazine Niacin Nitrate Phenylephrine LSD MDMA
