Final exam General Q Flashcards
1 Routs of drug administration (classification, comparative characteristics).
1-Entral : oral and sublingual
2-Parentral:
2.1 intervenous
2.2 IM
2.3 S.c
2.4 Interdermal
3-Others :
3.1 Oral for inhlation
3.2 interthecal
3.3 Topical
3.4 transdermal
3.5 Rectal
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1-Oral : easily self administered, and toxicity and overdose of the drug may come with Antidote
-And we have 2 types :
1.1 Enteric caoted preparations :
Its a chemical envalope thats portacts the drug from the stomach acid to dilevred it to the intestines which is less acidic EX aspirin
1.2 Extended release preparation :
Provides controlling of the drug dose for slower absorption
2-Sublingual/Buccal :
Easy admensterd , fast absorption, Skips the GU environment and also skips the FPM
3-Parentral : goes directly to the systemic circulation and used for the drug to pass the Absorption of GI tract and provide rapid onset
3.1 IV : provides rapid effect and macimum degree of control over the drug delivered
3.2 IM : can be in aqueons Solution or in special depot preparation
3.: S.B : slower then IV injection and low risk or hemolysis or thrombosis which is caused by IV
2 Transport of drugs through biological membranes. Factors affecting the drug absorption and distribution
1- ion channels:
1-1 the drug block it physically
1-2 receptor ion channel
1-3 through g-proteins receptor activate it which lead to Camp open the ion channel
——
—- transmembrane movement of the drug :
1-simple diffusion: the most important method of drug absorption
2-filtration: important for drug excretion by kidney
simple and filtration also known as passive transfer
3-active transport
4-facilitated diffusion:
active and facilitated also known as carrier -mediated
5-pinocytosis: its active process which energy dependent in which the drug is engulfed inside the cell
pinocytosis and facilitated and active known as specialized transporter
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2-enzymes:
2-1 the drug goes and bond with enzyme with reversible bond
2-2 irreversible bond like ( Organophosphate)
2-3 false substances: like Ldopa converted to be dopamine, so when the drug interact with the enzyme the enzyme false between the real L dopa and fake L dopa which is the the drug and prevent synthesis of dopamine
———
3- carrie molecules or transporter :
3-1 increase the carrier molecules or decrease it
———————–
-factors that effect the absorpation :
- there is 2 types of factors
1- factors related to the drug :
1-1 molecular size
1-2 dose : increase of the dose lead to increase of the absorption
1-3 lipid salability ( pKa) : drug ionization
2- factors related to the body :
2-1 route of administration
2-2 integrity of the absorption surface
2-3 blood flow
3 Receptor mechanisms of drug action. Full and partial agonists, antagonists and agonists-antagonist.
-Dif of affinty : is the ability of substance to bind to a biological target resulting of formation of substance- receptor complex
-agonist: its substance with affinity and intrinsic activity
- the agonist can reach maximum effect which can be expected from the medicinal agent and thats called = efficacy
-another term is the potency: which is determined by the concentration in which the substance produced 50% of the effect
— types of the agonist :
1-full agonist : its the ligand that bind to receptor and produce the maximum cellular response
2-partial agonist : its the ligand which bind to the receptor with internisc activity greater then 0 but less the 100%
— type of response in the agonist
1-graded response : its response proportionally related to the dose which mean increasing of the dose will lead to increase of response
2-quintal response :the response about all or non Ex the epilpicy and arethmeia 
–we have 2 types :
1- comparative antagonist : have affinity but no intrinsic activity ( blocker ) and bind at the same site of agonist
2- non-competitive antagonist : occurs when antagonist occupies which so called allosteric binding site in receptor
(micro molecule non receptor sites which regulate the receptor activity
4 Classification of drug receptors: G-protein coupled receptor, principles of signal transduction, examples of pharmacological ligands
-receptor: its protein micro-molecule embedded in the cell membrane has extra cellular level and intra cellular level
-if the drug bind to receptor called ligands , if the ligand activate the receptor will be called agonist , and if blocked or inhibit the receptor called antagonist
—-types of receptor:
1-ligand gated-ion channel :after binding of agonist or antagonist to ion channels receptor the transmembrane conductance of specific ion increased or decreased and that causing a change in vital activity of cell membrane
2-G protein couples receptor :they are located in cell membrane and they implement there responses through the second massinger and when agonist bind to it a further signal performed and change a number of enzymes in cell or coupled ion channel
-signal transducation :
Gi > increace adenyl cycles > increase Camp > and activation of specifc protines such as IP3/DAG in alpha repctor ,
-Exampl : insuline recptor
3- enzyme linked receptor: usually has extra cellular domain for ligand which is cytokines
and intracellular domain which is
tyrosin kinase
4-receptor regulating gene transcription
receptor regulating gene transcription are termed nuclear receptor some of them located in the cytoplasm and migrate to nucleus only after binding to ligand
5 Classification of drug receptors: receptor with intrinsic ion channel, principles of signal transduction, examples of pharmacological ligands.
-receptor: its protein micro-molecule embedded in the cell membrane has extra cellular level and intra cellular level
-if the drug bind to receptor called ligands , if the ligand activate the receptor will be called agonist , and if blocked or inhibit the receptor called antagonist
—-types of receptor:
1-ligand gated-ion channel :after binding of agonist or antagonist to ion channels receptor the transmembrane conductance of specific ion increased or decreased and that causing a change in vital activity of cell membrane
-Exampls :
1-nicotonic recptor : ACh
2-GABA Recptor : gamma amino bturutic acid
2-G protein couples receptor :they are located in cell membrane and they implement there responses through the second massinger and when agonist bind to it a further signal performed and change a number of enzymes in cell or coupled ion channel
-signal transducation :
Gi > increace adenyl cycles > increase Camp > and activation of specifc protines such as IP3/DAG in alpha repctor ,
-Exampl : insuline recptor
3- enzyme linked receptor: usually has extra cellular domain for ligand which is cytokines
and intracellular domain which is
tyrosin kinase
4-receptor regulating gene transcription
receptor regulating gene transcription are termed nuclear receptor some of them located in the cytoplasm and migrate to nucleus only after binding to ligand
6 Classification of drug receptors: receptor tyrosine kinase, principles of signal transduction, examples of pharmacological ligands.
-receptor: its protein micro-molecule embedded in the cell membrane has extra cellular level and intra cellular level
-if the drug bind to receptor called ligands , if the ligand activate the receptor will be called agonist , and if blocked or inhibit the receptor called antagonist
—-types of receptor:
1-ligand gated-ion channel :after binding of agonist or antagonist to ion channels receptor the transmembrane conductance of specific ion increased or decreased and that causing a change in vital activity of cell membrane
-Exampls :
1-nicotonic recptor : ACh
2-GABA Recptor : gamma amino bturutic acid
2-G protein couples receptor :they are located in cell membrane and they implement there responses through the second massinger and when agonist bind to it a further signal performed and change a number of enzymes in cell or coupled ion channel
-signal transducation :
Gi > increace adenyl cycles > increase Camp > and activation of specifc protines such as IP3/DAG in alpha repctor ,
-Exampl : insuline recptor
3- enzyme linked receptor: usually has extra cellular domain for ligand which is cytokines
and intracellular domain which is
tyrosin kinase
-Ex : insuline recptor
4-receptor regulating gene transcription
receptor regulating gene transcription are termed nuclear receptor some of them located in the cytoplasm and migrate to nucleus only after binding to ligand
7 Classification of drug receptors: intracellular receptor regulating gene transcription, principles of signal transduction, examples of pharmacological ligands.
-receptor: its protein micro-molecule embedded in the cell membrane has extra cellular level and intra cellular level
-if the drug bind to receptor called ligands , if the ligand activate the receptor will be called agonist , and if blocked or inhibit the receptor called antagonist
—-types of receptor:
1-ligand gated-ion channel :after binding of agonist or
2-G protein couples receptor :they are located in cell
3- enzyme linked receptor: usually has extra cellular domain
4-receptor regulating gene transcription
receptor regulating gene transcription are termed nuclear receptor some of them located in the cytoplasm and migrate to nucleus only after binding to ligand
example : glicocorticoids
8 Pharmacokinetics: absorption, presystemic elimination, bioavailability
DF : its the passage of the drug from site of administration to the plasma
— main site of administration:
1-oral. 2-sublingual 3-rectal 4-inhalation 5- injection
—- transmembrane movement of the drug :
1-simple diffusion: the most important method of drug absorption
2-filtration: important for drug excretion by kidney
simple and filtration also known as passive transfer
3-active transport
4-facilitated diffusion:
active and facilitated also known as carrier -mediated
5-pinocytosis: its active process which energy dependent in which the drug is engulfed inside the cell
pinocytosis and facilitated and active known as specialized transporter
9 Pharmacokinetics: bioavailability, apparent volume of distribution.
pharmacokinetics : the effect of the body on the drug
it has 4 parts which is :
1-absorption
2-distribution
3-metabolism
4-elimination
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————–1-Absorption
DF : its the passage of the drug from site of administration to the plasma
— main site of administration:
1-oral. 2-sublingual 3-rectal 4-inhalation 5- injection
—- transmembrane movement of the drug :
1-simple diffusion: the most important method of drug absorption
2-filtration: important for drug excretion by kidney
simple and filtration also known as passive transfer
3-active transport
4-facilitated diffusion:
active and facilitated also known as carrier -mediated
5-pinocytosis: its active process which energy dependent in which the drug is engulfed inside the cell pinocytosis and facilitated and active known as specialized transporter
- factors effect the drug absorption:
- there is 2 types of factors
1- factors related to the drug :
1-1 molecular size
1-2 dose : increase of the dose lead to increase of the absorption
1-3 lipid salability ( pKa) : drug ionization
2- factors related to the body :
2-1 route of administration
2-2 integrity of the absorption surface
2-3 blood flow
-The Henderson-Hasselbach Equation ( pKa):
-The Henderson-Hasselbach Equation expresses a relationship between the body compartment pH, the drug’s pKa (can be measured in the laboratory), and provides the ratio of acidic and basic forms of the drug
- clinical significant for pKa:
1- know the site of drug absorption from GIT
2-treatment of toxicity, with acidification or alkalization
Absorption% = Pka-PH
-the ion trap - the ion trap is mean that the drug will ionized in the cell and cant diffuse to the blood stream
-Ex: ion trap for aspirin
the ph pKa for aspirin is 3,5
ph of stomach is 1,5
ph of stomach cell same as plasma which is 7,4 - ## so if patient took a large dose of aspirin with empty stomach the aspirin will move to stomach and bcs both acidic the aspirin will diffuse to stomach cells but becs the stomach cells doesn’t change the ph bcs there is no food the wall stomach get injured could explode , and the patient start vomiting blood , but after a time the ionized aspirin will change chemically and get diffused to blood circulation-Bioavilabilty : - its the fraction of the drug that reach the systemic circulation after passing the ( absorption and first pass metabolism )
10 Pharmacokinetics: elimination, biotransformation, half-life. Microsomal enzyme inductors and
inhibitors.
——————–3-metabolism
—Df of metabolism and its main function: transfer the substance that entered the body which is lipid-soluble to water-soluble to be easy excreted
—- the major site of metabolism is the : liver but not the only
——- ceases of drug in the metabolism is 1 of these 4 :
1- active to inactive
2- active to active ex: codein to morphen
3-inactive to active : ex enaloprel to enalaprolant
4- from any shape to toxic: ex paracetamol to in Acitlypenzokinon
We have 2 Phases :
-Phase 1 :
- it has 3 types :
1-oxidation ( the important one )
2-reduction
3-hydrolysis
—-Phase 1 oxidation :
happend in the vesicles inside the hepatocytes there is a lot of enzymes group but we are interested in 1 group of them which call ( cytochrome P450 )
its family of enzyme consist of not less then 50 enzyme which is mixed function oxignesis
—-biotransformation : the most valuable enzyme of this family called (CYP3A4) this enzyme can metabolize 50% of the our drugs
—types of microsomal :
1- microsomal inducers : induce the cyp3a4
1-1 barbiturates
1-2 Rifampin
1-3 carbamezoampin
1-4 cigarettes smoking
2- microsomal inhibitors: inhibit CYP3A4
2-1cimatadene
2-2 ketokonzol
2-3 Erythromycin
2-4 grape fruit
——- Ex the contraceptive bills with cigarettes smoking or rifampin ( tuberculosis drug )
-Phase 2 :
-Phase 2 ( conjugated ) : phase 2 activated if chemistry of the drug doesn’t work with phase 1
— mechanism:
if the liver fail to metabolize with first phase , the liver will conjugate the drug with large molecules like acylation , sulfation but most of the time glucuronic acid , in neonates the primary pathway is sulfation , after conjugated with large molecule which is water-soluble the liver will excrete the conjugated molecule through bile then to intestine
—- enzyme inducer or inhibitor : its only available with ( groconail transfers )
- first pass metabolism:
Df : the first place at which drug could be metabolize partly before reaching the systemic circulation
—- cases of First pass metabolism:
1-passing through the liver without in first pass metabolism
2- first pass metabolism of drug partly in the live
3- the liver first metabolize the drug
100 % ex lidocaine ( we should look for another rout of administration)
- Bioavailability:
- its the fraction of the drug that reach the systemic circulation after passing the ( absorption and first pass metabolism )
- formula:
bioavailability=absorption – FPM result by percentage
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——————4-Elimination/ Execration
- elimination = excretion + metabolism
Clearance (Cl, ml/min.) – volume of blood plasma which totally cleared of drug per unit of time
Cl total = Clrenal + Clhepatic + Clother
– Most drugs are eliminated by first-order process. The amount of drug eliminated per unit of time does not remain constant. But fraction of drug eliminated per unit of time remains constant
Half-life – time necessary for the concentration of drug in the plasma to decrease by half
NB! drug eliminated after 4-5 half life
- Ways of drug excretion. Drug clearance. Factors that change the drug clearance. General principles of drug choosing in renal and hepatic insufficiency.
——————4-Elimination/ Execration
- elimination = excretion + metabolism
Clearance (Cl, ml/min.) – volume of blood plasma which totally cleared of drug per unit of time
Cl total = Clrenal + Clhepatic + Clother
– Most drugs are eliminated by first-order process. The amount of drug eliminated per unit of time does not remain constant. But fraction of drug eliminated per unit of time remains constant
Half-life – time necessary for the concentration of drug in the plasma to decrease by half
NB! drug eliminated after 4-5 half life
-Ex for Renal faluir : ACE inhibitors and ARBs
-ex for Hepatic insufficincy : fentanyl and ciprofloxacin
- Drug interaction (pharmaceutical, pharmacokinetic, pharmacodynamic).
1-pharmaceutical : ex mixing acidic drug with alkaline drug
2-pharmacokinetic :Pharmacokinetic drug-drug interactions occur when a drug alters the disposition (absorption, distribution, elimination) of a coadministered agent. Pharmacokinetic interactions may result in the increase or the decrease of plasma drug concentrations.
-ex if a patient has anemia and he take medicine for the anemia and then he took a medicine for stomach acid which is ( antacid ) the antacid prevent the absorption of iron which he needed for the anemia so this is a antagonism on level of the absorption
3-pharmacodynamic : Pharmacodynamic drug-drug interactions (DDIs) occur when the pharmacological effect of one drug is altered by that of another drug in a combination regimen. DDIs often are classified as synergistic, additive, or antagonistic in nature, albeit these terms are frequently misused.
-One example of a pharmacodynamic drug-drug ADR is the interaction between NSAIDs and antihypertensive agents. The inhibition of prostaglandin synthesis by NSAIDs increases vascular tone, which decreases the efficacy of antihypertensive drugs
- Effects of repeated use of drug (tolerance, dependence, accumulation, sensibilisation)
-repeated administrations of the drug often lead to change on the responsive of the drug receptor , the receptor may become insensitive duo to much agents stimulation
1-Tolerance : prograssive decreases of the drug response with successive administrations , this may occurs duo to prolonged exposure of the drug leas to decrease the number of the receptors
2-Depnedce : it’s referring to the physical condition in which the body has adopted to the presence of the drug and known as withdrawal symptoms ex Opioids
3- sensibilisation: Sensitization is defined as an enhanced response to a drug after repeated exposure to the same dose of the drug.
4-Accumulation : is simply a reflection of how much drug is being added to the body relative to how much is being eliminated from the body during a defined period of time. And that ratio can be controlled by changing the dosing frequency. (redestrbaion )
- Drug nomenclature. Drug doses: therapeutic, maintenance, toxic doses
-Drug nomenclature :
1-chemical name
2- non-propitry name : genetic name referred to a scientist
3-propitry name : commercial name
-Drug doses :
-therapeutic index : is commonly used to quantify the therapeutic window
and its Ti = Td50 / Te50
-TD50 : its the dose that produces toxic effects of 50% of population
-Te50: its the dose that produces therapeutic effect of 50% of the population
its starting from up to down ( healthy to lethal )
1-threshold dose
2-mean therapeutic dose
3-maximum therapeutic dose
4-toxic dose : An infective dose that causes disease in half the subjects exposed to it. median lethal dose. Abbreviation: LD50. The amount of a substance
5- lethal dose
