Pharma Flashcards
2 methods used to measure the duration of exponential process
Time constant and half/life
After one half life … of the process is still remaining where 2 half life … and 3 half life’s … of process still remaining
50%
25%
12.5%
After one Time constant … of the process remaining, where 2 time constant … and 3 time constant … of the process still remains to complete
37%
12.5%
5%
Time constant for breathing circuit is
Volume of circuit/fresh gas flow rate
Time constant for lungs =
FRC / minute ventilation
Context sensitive half life is …
The time taken for drug concentration to fall by 50% after DC
ED95 means
The dose of drug that is required to produce a specific response in 95% of the population exposed to the drug
ED 95 for NMB
Is the amount of drug needed to decrease the twitch height by 95%
1st order kinetics
Rate of decrease of plasma concentration of the drug depends of plasma concentration of the drug
Zero order kinetics
The plasma concentration of drug decreases at a constant rate
Drug dosing in RF relation to volume of distribution
Volume of distribution is increased and clearance reduced leading to increased loading and dosing interval
Drugs acting on GABA receptors
GABA-A
GABA-B
GABA-A -> Cl channel opening (thiopental, propofol, BZDs, etomidate)
GABA-B -> K channel opening (Baclofen)
Ketamine acts on
noncompetitive antagonist of NMDA Ca channel pore
Baclofen acts on
Agonist of GABA- B receptors both pre and postsynaptic
Ion channels and drugs act on
Ca
Cl
Na
K
Gaba + ketamine -> Ca
Thiopental, propofol, Etomidate -> Cl
Local anesthetic, phenytoin, NMB -> Na
Baclofen -> K
Agents that work on cGMP and cAMP
Nitric oxide
Glucagon, insulin, Epi, NorEpi, milrinone, PGs -> all cAMP
Dose of oral Versed is higher then IV because …
High first pass metabolism in liver
0.5-0.7 mg/kg body weight
Location of brain opioid receptors
Periaqueductal gray matter
Amygdala
Corpus striatum
Hypothalamus
At spinal -> substantia gelatinosa
Clinical effect of mu opioid receptors
Spinal and supraspinal analgesia
RS depression
Physical dependence
Ms rigidity
Clinical effect of kappa opioid receptors
Sedation and spinal analgesia
Clinical effect of delta opioid receptors
Analgesia and behavioral
Clinical effect of sigma opioid receptors
Dysphoria and hallucination
The ceiling effect of Nalbupine is due to ..
It’s partial agonistic activity
What’s the reason of rapid action of Alfentanil? And it’s short duration?
Low pKa
Where it has low VoD and it’s rapid metabolism in liver makes it short duration of action
The rapid duration of action of ramifentanil is due to its …
Rapid metabolism by plasma esterases (its metabolism not dependent on liver like alfentanil)
Drugs metabolized by esterases:
Esmolol
Etomidate
Remifentanil
Atracurium
Succinylcholine
Ester local anesthetics
The onset of action of opioids depends on …
Lipid solubility (how rapid it diffuses into CNS and offset of action is due to rapid redistribution from CNS)
Morphine has the lowest lipid solubility and therefore it’s onset of action is slowest sand had longest duration of action
Onset of opioid depends on …
pKa and VoD, as well as lipid solubility
Meperidine has the highest (8.5) -> slowst onset of action
Alfentanil has the lowest (6.5) -> fastest onset of action.
VoD of morphine, meperidine, and fentanyl is same 3-5 but because fentanyl has the highest lipid solubility of all (~580 vs 1 for morphine and 25 for meperidine) makes it fastest onset of action
10 of IV morphine equaled to … po
And 1 mg IV dilaudid = … po
30 mg
1 mg dilaudid IV = 5 mg po
IV-Epidural-Intrathecal opioid dosing
Morphine
Dilaudid
Fentanyl
Morphine: 10 mg IV = 1 mg Epidural = 0.1 mg intrathecal (very hydrophilic)
Dilaudid: 1mg IV= 0.2 mg Epidural = 0.04 mg intrathecal
Fentanyl: 100 mcg IV = 33 mcg Epidural = 6-10 mcg intrathecal (very lipophilic)
Among the opioids, … prolongs QT interval
Methadone
…. is prodrug opioid and needs to be converted into active metabolites
Codeine
Metabolic product of … is … and it’s accumulation in RF causes seizures activity
Meperidine is nor-meperidine
An opioid that has local anesthetic activity is …
Meperidine
Opioid effects that can be reversed with Nalaxone are …
RS depression
Analgesia
Pruritus
Can’t reverse (constipation, NV, ms rigidity, Miosis).
Propofol distributes to vessel rich, lipid rich organ (brain) and ptn become anesthetized. Ptn wakes up from single dose of propofol due to …
Redistribution
The primary organ for redistribution of propofol is
Ms skeletal > liver and kidneys
Redistribution to moderate BF and lipid content organs
The dose of thiopental in elderly should be reduced because of …
Decreased inter-compartment clearance
In obese patients, all drugs should be doses based on lean body weight except … doses per TBW to obtain …
Succinylcholine
Ideal intubating conditions during RSI
Induction agents act at brain and size of brain is similar in obese and non-obese patients (NMB are water soluble agents and the total body water is similar in both obese and non-obese patients).
Lean body weight = ideal Weight + 20%
What makes Etomidate ideal for ECT?
Because it increases seizure duration and often these patients failed previous treatment due to short seizure duration
Propofol compared to Etomidate
Etomidate associated with more pain on injection, myoclonus, NV. And has the association of adrenocortical suppression.
The only advantage over propofol is that has less incidence of hypotension
Propofol infusion syndrome clinical features
Met. Acidosis Hypotension Bradycardia resistance to treatment HyperTGs Rhabdomyolysis Hepatomegaly ARF
Ketamine CI in … and indicated in …
Idiopathic hypertrophic subaortic stenosis
Cardiac tamponade, TOF, hypothyroid, asthma
Ketamine indicated in cardiac tamponade because…
It increases HR and SVR which is beneficial
Drugs not safe in porphyria …
Barbiturates Etomidate Chlordiazepoxide Nitrazepam Flunitazepam Hydralazine Alpha methyl dopa OCP Steroids
(Propofol is safe)
Nitrous should be DC prior to … during vitrectomy for retinal detachment
Injection of suphur hexafluride
Which would nitrous expand rapidly, pneumothorax or air bubbles in the blood
Air bubbles as there is no tissue barrier
% of nitrous and size of pneumothorax increased
50% -> x2
66% -> x3
75% -> x 4
Volatiles and their metabolism %
Halothane 20%
Sevo and Enflurane 2%
ISO 0.2%
Des 0.02%
Why Des needs a special heated vaporizer?
Because it’s saturated vapor pressure (SVP) is close to atmospheric pressure ~ 680 mmHg and it’s boiling point is close to room temperature ~ 21 C
This property results in fluctuations of vaporizer output when the vaporizer is exposed to different ambient temperatures
Rapid FA/FI results when …
Increase inspired agent concentration
Increased minute ventilation
Decreased CO
Low blood gas solubility coefficient
Why N2O has higher FA/FI then Des even though Des has lower B/G solubility coefficient (0.42 compared to 0.45 for N2O)?
Due to higher concentration effect
MAC for each volatiles
104 N2O
6 Des
2 Sevo
- 8 Enflurane
- 2 Iso
- 8 Halothane
B:G coefficient for each volatiles
- 42 Des
- 46 N2O
- 6 Sevo
- 4 Iso
- 7 Enflurane
- 3 Halothane
The lower the faster FA/FI (except N2O faster then Des because of its higher concentration)
All volatiles increases HR and useful in ….
Except … therefore it is useful in IHSS
Cardiac tamponade, AR, MR
Halothane dose not increase HR and therefore useful in IHSS
N2O effect in myocardium
It’s depressant (causes symptomatic stimulation)
HD goals in IHSS
Increase preload, decrease myocardial contractility, avoid tachycardia, maintain afterload
Therefore ketamine is CI
Halothane is useful
HD goals in Cardiac tamponade
Maintain HR, increase preload and afterload (fast full and tight).
Ketamine is ideal
HD goal in MR?
Mild tachycardia and vasodilation
HD goals in AS and MS?
Avoid tachycardia and decrease in afterload
Avoid extreme bradycardia
Uptake of volatiles in neonate is faster than adults because
Increased ventilation and CO result in faster delivery of agent and rapid induction
On other hand, that low CO results in increase FA/FI
MAC requirement increases up to age of … and then decreases.
Only one volatile exception …
6 months
Sevo -> MAC is highest in neonates and then steadily decreases
MAC is unaffected by …
Duration of anesthesia
Gender
Alkalosis/Acidosis
Hypo/hyperthyroidism
Hypo/hypercarpia (paCO2 <90)
MAC decreases in …
Hypothermia Hypoxia Acute alcohol Sever hypotension Lithium Narcotic Ketamine Chronic amphetamines Cholinesterase inhibitor Elderly Pregnancy *** Hyperbaric chamber
MAC requirement increases in …
Chronic alcohol Acute amphetamines MOA inhibitor Cocaine Hyperthermia Hypertension Neonates
Hyperbaric chamber anesthesia decreases the MAC of volatiles due to …
Nitrogen narcosis
N2O can be used as sole anesthetic agent in …
Hyperbaric conditions
A volatile that if it’s concentration changed rapidly results in symptometic stimulation?
Desflurane
Right to left shunt results in inhalation’s induction … and IV induction …
Where left to right shunt …
Slow inhalation all and rapid IV induction with Rt->Lt shunt
IV induction delayed with Lf->Rt shunt, no effect on inhalational
High altitude effect on flow meter of gas compared to sea level?
Flow increases at higher flow rate (due to decreased density)
However, flow is unchanged at low flow rates because the viscosity is same
High altitude effect on vaporizer output of gas compared to sea level?
Output increases as the potency decreases at high altitude but however the change in dial setting is not indicated at high altitude
Exception is Desflurane -> no change in output as the vaporizer is electrically heated.
High altitude effect on induction of gas compared to sea level?
Slower at high altitude
Factors producing increased Carbon Monoxide?
Desflurane Low gas flow Dry absorbent Barely me > sodalime Increased temp of absorbent
Decreased in single twitch height seen in both DNMB and NDNMB, but however the tetanus fade and post tetanus potentiation seen only in …
The potentiation of the block with anti cholinesterase seen only with …
NDNMB
DNMB
The order of onset/recovery of NMB from first to last …
Diaphragm > laryngeal muscle > adductor pollicis
Tetanus fade explained by ….
Post tetanus facilitation explained by …
The depletion of Acho stores in prejunctional area results in decreased Acho release in synaptic cleft -> tetanus fade
Following a pause, post tetanus stimulation is applied. During this pause period Acho reacumulates In presynaptic vesicles and subsequent stimulation results in increased release of Acetylcholine
The termination of action of 2 NMB … by diffusion away from NM junction are …
Succinylcholine and pancuronium
Acetylcholinesterase is not present in plasma, it’s present at …
Where pseudo cholinesterase only present in …
NM junction
Blood
3 main Antibiotics dose not potentiate NM blockade are …
Penicillin, cephalosporins, erythromycin
The best test for NMB recovery is …
TOF ratio > 0.9
Best clinical test of adequate NMB recovery …
Sustained leg lift in neonates
Mastered muscle tone in adults
(Sustained head lift for 5 sec, can be obtained with TOF ratio of 0.5 and at this point respiratory muscle have not yet completely recovered).
The exertion of neostigmine and pancuronium is prolonged in … patients
RF
Debucaine is …. local anesthetic and number measured is % of
Amide
% of inhibited Palawan cholinesterase (normal should be > 80% inhibition as indicated presences of enzyme)
Heterozygous-> 40-60
Homozygous-> 20 (this develops periods of apnea after succinylcholine)
Psudocholinesterase (butyrylcholinesterase) is responsible for metabolism of …
Succinylcholine
Ester local
Mivacurium
Second dose of succinylcholine results in
Asystole 2/2 hypokalemia
Bradycardia 2/2 cavalry stimulation (pretreatment with atropine required).
Succinylcholine dose or dose not produce hyperkalemia response in Cerebral Palsy patients?
Dose NOT
Burns and paralyzed patients are sensitive to … and resistant to … NMB
Sensitive to DNMB
Resistant to NDNMB
due to presence of extrajunctional receptors
Mg prolongs both DNMB and NDNMB because….
It decreases the release of acetylcholine at NM junction
Electrolytes abnormalities that prolongs NM blockade
HYPo K and Ca
Hyper Na and Mg
Because hypoCa prolongs NM blockade, the expected blockade in hyperparathyrodisim patient is …
Shortened
HyperCa antagonized the effect of NMB
The effect of carbamazepine and phenytoin on NMB depends on duration of treatment
Chronic therapy -> shortens of NDNMB
Acute/one dose -> prolongs NDNMB
CCB prolongs/shortens NMB?
Prolongs it (low Ca -> prolong blockade).
Drugs inhibits psudocholensterse and therefore prolongs action of succinylcholine
Nitrogen mustard Trimetaphan Ecothiopate Pancuronium Anti cholinesterase Metoclopramide
(Mivacurium is partly metabolized by psudocholensterse).
Ester local anesthetic potentiate/shortens anticholinesterse (pyridostigmine or neostigmine)?
Potentiate it
NMB in elderly to consider? Why NMB dose should be reduced in elderly?
Slow action in low CO
Decreased volume distribution in low muscle mass
Prolonged action in decreased renal and hepatic function
(So dose should be reduced)
Why the following drugs dose not cross placenta?
Succinylcholine
Rocuronium
Chlorprocaine
Bupivacaine
Highly ionized
Large molecule
Rapid metabolism
High protein binding
The most local anesthetic crosses placenta
Lidocaine then bupivcaine
When neostigmine dose increased, there is a … and further dose induced the depolarizating block
Ceiling effect
Muscurinic effect of neostigmine?
Increased secretion
Bronchi constriction
Increased GI motility
Miosis
Insulin, heparin, LMWH, NDNMB dose or dose not cross placenta?
Dose NOT
Following anticholinargics dose or dose not cross placenta?
Physostigmine, atropine, scopolamine-> crosses placenta
Neostigmine, pyridostigmine, glycopyrolate-> dose NOT
Levorotatory isomers disperse the polarizing light to the …
Dextrorotatory isomers disperse the polarizing light to …
Left
Right
(Rovivacine is an enatiomer containing only levorotatory isomers)
(Bupivacaine has both levorotatory and dextrorotatory isomers).
Local anesthetic potency depends on … , duration on …, and onset on …
Lipid solubility-> potency
Protein binding, lipid solubility-> duration
Onset -> pKa, concentration
Why chlorprocaine has rapid onset despite its low pKa?
Because it’s administered in higher concentration
Why chlorprocaine has the shortest duration of all locals when administering it epidurally?
Because it rapidly metabolized by plasma cholinesterase
Methemoglobinemia associated with which local anesthetic?
Prilocaine > benzocaine
Treated with methylene blue and ascot if acid
CI for methyl blue?
G6PD deficiency and patients on SSRI
Patients who are more risk for methemoglobinemia?
G6PD deficiency patients
Advantage of Ropivacaine and Levobupivacaine over bupivacaine are …
Less motor block and less cardiac toxicity
Earliest sign of lintravascular injection of local anesthetics are …
Without Epi -> tinnitus and cirumoral numbness
With Epi -> Tachycardia
RFs of Transient neurological symptoms (TNS) after spinal
Lidocaine > mepivacaine > procaine > bupivacaine
Highest incidence with 5% hyperbaric lidocaine
Higher concentration of local
Lithotomy position
Highest to lowest of blood local anesthetics are …
Intercostal > caudal > epidural > brachial > femoral/sciatic
Tumescent Lidocaine used for
Liposuction
Concentration 0.025% -0.1%
Peak concentration at 12-14 hours
Declining time: over 6-14 hours
Epinephrine dose in bag: 1:1,000,000
Why metoclopramide is CI in parakinsons disease patients?
Extra pyramidal symptoms (rigidity)
Onset time of H2 blockers?
30 min -> IV
60-90 -> po
Effect of Ranitidine, Metoclopramide, Na-citrate on gastric volume and pH?
Metoclopramide only decreases gastric volume.
Na-Cirtate only increases gastric pH
Ranitidine decreases gastric volume and increases pH
Metoclopramide effect on GI system?
Increases LE sphincter tone
Increase gastric emptying
Decreases gastric volume
No change in pH
Drugs increases LE sphincter tone?
Metoclopramide
Neostigmine
Succinylcholine
Drugs has no effect on LE sphincter tone?
H2 blockers PPI inhibitors Propofol Remifentanil Precedex
Drugs lower the tone of LE sphincter?
Morphine
Meperidine
High dose propofol (normal dose has no effect)
BDZs
TCA
Anticholinergics
Clonidine and precedex are both alpha-2 …. and both results into hypotension and bradycardia but bradycardia seen more with … and hypotension seen more with …
Agonists
Hypotension-> precedex
Brady -> clonidine
Toxic effect of:
Methotrexate Amiodarone Bleomycin Cyclophosphamide Doxorubicin/Donorubicin Vincristine Cyclosporine Cisplatin
Megaloblastic anemia Pulm fibrosis Pulmonary fibrosis Hemorrhagic cystitis Irreversible CMP Peripheral neuropathy Renal toxicity Peripheral neuropathy
SE of Amiodarone
QT prolongation
Pulm fibrosis
Hypo/Hyper thyrodisim
Management of long QT?
Mg, k replacement
Long term; BB, pacing, left sympathectomy in refractory cases
Avoid Amiodrone
Etiology of prolong QT?
Congenital
Acquired;
- quinidine
- procainamide
- sotalol
- amiodarone
- macrolides
- TCA
- phenothiazines
- droperidol
- haloperidol
- TMP-SMX
- Zofran
SE of hydrochlorothiazide?
Decreases -> K, Cl, Na, and platelets
Increases -> UA and Ca
Diuretic works on proximal tubule?
Acetozolamide (carbonic anhydrase inhibitor-> inhibits reabsobtion of bicarbonate)
Diuretics works on Medullary portion of ascending limb of loop of henle?
Furosemide
Bumetanide
Ethacrynic acid
Mannitol
Inhibits Na/K/Cl co-transport-> prevents NaCl reabsorption
Diuretics work on Distal tubule?
Hydrochlorothizide
Inhibits Na + Cl reabsorption
Diuretics works on collecting duct?
Amiloride
Triamterene
Inhibits Na channels
Spironolactone
Aldo antagonist-> inhibits Na reabsorption and K secretion
Diuretics causes hyperkalemia
Spironolactone
Amiloride
Metabolic effects of Diuretics? All causes metabolic acidosis except …
Furosemide and thiazides causes metabolic Alkalosis
Diuretics causes venodilation and reduces preload
Furosemide
SE of nalaxone?
Tachycardia
Hypertension
SE flumazanil
NV and seizures
SE of Dantrolene
Muscle weakness
SE of Ritodrine/terbutaline/Albuterol? Which are B2 agonists
Hypotension Tachycardia Hyperglycemia Pulm edema Hypokalemia
Medications reduces biliary spasms?
Atropine
Glucagon
Nitroglycerin
Used in
- hypoglycemia
- BB overdose
- biliary spasm
Amiodarone is class … anti arrhythmic which prolongs the …. of phase … by …
At the SA node it blocks different channels?
Class 3 Prolongs depolarization (phase 3) By K channel blockade
It blocks Ca channels at the AS mode and prolongs refractory period
Acute SE of Amiodarone
Peripheral vasodilation-> Hypotension
And Bradycardia
Indication for ACE inhibitor? And CIs?
CHF, Anterior MI with low EF, and DM-nephropathy
CI: pregnancy, BL RAS, prior angioedema
Alpha 1 receptors location? Vs alpha2?
Postsynaptic In Vascular SM -> stimulation leads to vasoconstriction
Presynaptic and stimulation decreases release of NorEpi
Beta 1 receptors location vs Beta 2?
Myocardium and stimulation causes positive intropic + chronotropic
Beta 2 causes vasodilation and positive chronotropic
Adrenergic agents and their receptor action:
Dopamine
Dobutamine
NorEpi
Epi
All beta + alpha
Mainly B1 (mild Beta2 and alpha1)
The ones alpha1 + beta1
The ones (alpha1+beta1) and beta2
Nitroglycerin effect
Reduces preload, myocardial wall tension, and O2 consumption.
Why Ephedrine won’t be effective in chronic cocaine users?
Due to catacholamine depletion at the adrenergic nerve ending.
Milrinone is a …. inhibitor.
1) It decreases intracellular breakdown of … which leads to increased their levels in …
2) increases intracellular….
Phosphdiesterase inhibitors
Decreases breakdown of cAMP and therefore increases their levels in myocardium and vascular SM
Increases intracellular Ca
Milrinone effect?
Decreases afterload via decreased SVR, increases myocardium contractility, and CO
It has no effect on Alpha or Beta
Toxic effect of N2O are due to?
Methemoglobinemia
Nitrogen dioxide
Epinephrine benefits in anaphylaxis by … and in cardiac arrest by …
Stabilizing mast cell membrane
Increase afterload and improve cerebral and cardiac perfusion
LMWH compared to SQH
Greater bioavailability
Longer duration of action
Has greater anti Xa than Anti IIa activity
Lower risk for HIT
LMWH excreted through renal, where SQH …
Reticuloendothelial system. At higher dosage it’s excreted through kidneys
Antiplateltes classifications;
Cyclooxygenase inhibitor->
ADP receptors inhibitors ->
G IIb/IIIa inhibitors->
Adenosine reuptake inhibitors ->
ASA
Clopidogril, ticlopidine, prasugrel
Abciximab, eptifbatide, tirofiban, deofibrotide
Dipyridamole
Direct thrombin inhibitors
Hirudin
Bivalirudin
Lepirudin
Plasminogen activators
tPA
Urokinase
Streptokinase
Plasminogen inhibitors
Epsilon amniocaprionic acid
TXA
Tertiary amine anticholenrgic that crosses BBB and causes CNS excitation ….
Tertiary amine anticholenrgic that crosses BBB but causes sedation ….
Atropine
Scopolamine = sedation
Anticholinergic causes Mydriasis in order of more occurrences
Scopolamine > atropine > glycopyrolate
Where Antisialagouge;
Scopolamine > glycopyrolate > atropine
2 CNS disease that anticholenirgics are CI?
Alzheimer’s and Parkinson’s
DOC of acute asthma in a patient who is tachycardic?
Ipratripium (less absorption from bronchial tree)
D/C of metformin is not recommended not …
Normal Kidney fiction presenting for elective surgery or prior contrast CT.
Herbals that inhibits platelet aggregation
Garlic
Ginkgo
Ginseng (it also lowers blood glucose).
Features of salicylic poisoning
Hyperpyrexia
Res. Alkalosis
Metabolic acidosis
Treatment of organophosphate
Atropine
Pralidoxime
SE lithium
Leukcytosis Hypothyroid DI AV block Sedation Hypothermia Seizures Potentiate both DNMB and NDNMB
First vs Zero order kinetics?
Zero -> a fixed amount of drug eliminated
First -> fixed % of drug elimination (every given time, t1/2 of drug eliminated).
