Pharmacology

Question 1

What your body dose to the drug is

Answer 1

Pharmacokinetics

-absorption (route of administration)

• distribution: (this quantified by volume of distribution)
  — solubility
  —- ability of drug to pass through cell membrane.
  —- quantified by partition coefficient
  — the bigger partition coefficient is the more soluble, the more it crosses the membrane

—ionization
—-the cross of drug through cell membrane based on pH difference

—protein binding
—-less bound -> more free the more action of drug
—-albumin binds to acidic drugs
—-alpha-1 glycoproteins binds to basic

• metabolism/elimination
  —liver (phase 1: oxygenation, reduction, hydrolysis, phase 2: consecration)
  —organ clearance
  —first order elimination (1st t1/2 50%, 2nd 25%, 3rd 12.5%)
• quantitative modules
  —redistribution
  —Context-Sensitive t1-2
  —uptake by vessel rich group vs vessel poor groups

Question 2

What the drug dose to your body is

Answer 2

Pharmacodynamics

• receptor binding (drug-drug binding, same site agonist-antagonist, indirect agonist/antagonist)
• drug effect (potency vs efficiency, competitive antagonist vs irreversible antagonist, tolerance vs tachyphlaxis, synergy vs additivity)
• drug rxn (anaphylaxis vs anaphlactoid).

Question 3

Potency can efficacy

Answer 3

Potency-> the amount of drug needed to produce effect

Efficacy -> max possible effect at infinite drug

Question 4

Therapeutic index is

Answer 4

If ED50 means effective dose in 50% of ppl

And LD50 is the lethal dose in 50% of ppl

Then TI is the difference between ED50 & LD50 (grater TI = sage drug)

Question 5

Competitive antagonist effect when agonist present and effect on agonist potency?

Answer 5

Adding antagonist would make the agonist less potent but if you increase agonist concentration will comparatively win its action and eventually reach same efficacy as if agonis given alone but with increase its concentration

So adding competitive agonist to agonist, will make the agonist less potent than if it given alone

Question 6

Irreversible antagonist effect if given with its agonist

Answer 6

By giving more concentration of agonist in presence of irreversible antagonist will not overcome the effect of antagonist (unlike competitive antagonist with agonist) because they are competing at not the same receptors

Question 7

Tolerance vs tachyphlaxis

Answer 7

Drug causing regulation of receptor or decreases receptor sensitivity as a response to high concentration

Tachyphlaxis is successive doses have progressively decreased effect (ephedrine, opioids, nitroglycerin, local anesthetic, dobutamine, ddVAP, hydralazine, Metoclopramide, ranitidine)

Question 8

Synergy vs additivity

Answer 8

Indicates the stimulation of compiled effect of 2 agents are greater then the sum of 2 individual agents

Additivity is the total effect of 2 agents is similar to the sum of the effect of individual agents.

Question 9

Anaphylaxis vs anaphlactoid

Answer 9

Ag-Ab (IgE) complex bind to mast cell releasing histamine

Where anaphlactoid is not IgE mediated, based on stimulation of release. Mostly complement pathway involvement

Trap tase test diagnose anaphylaxis as this (traptase) releases by mast cell

Question 10

How inhaled anesthetic work?

Answer 10

We believe it works by potentiating inhibitory currents within the CNS or downregulation of excitatory stimulation within CNS which results into overall downregulating the neronal activity of CNS to the point where unconscious achieved.

Question 11

Uptake of inhaled anesthetic depends on

Answer 11

Solubility (عكسي)
CO (عكسي)
PA - Pa

Shunt (right to left decreases rate of induction)

Question 12

Second gas effect or concentration effect

Answer 12

Is effect of N2O, due to its high solubility than the other gases, it will be picked up by circulation from alveolar faster, leaving the other gases in alveoli (more concentrated) in alveoli than what you deliver

Question 13

CV effect by gases

Answer 13

SVR -> decreased (more with iso & Des)

HR -> all increased except halothane (cardiac depressant )

CO & BP -> all decreases except N2O

Coronary vasodilation-> only halothane and iso

Question 14

RS effects of gases

Answer 14

All decreases, Tv, PaCO2 response, FRC and they all increases dead space

For RR -> all increases it

Bronchodilation
Decreases mucocilliary function and surfactant production
Attenuated HPV

Question 15

CNS effect by gases

Answer 15

CBF-> all increase
ICP-> all increase
CMRO2-> all decreases (except N2O)
EEG-> all decreases

Seizures threshold-> all decrease (more with iso & Des)

Latency-> all increase
AMP-> all decreases

Question 16

Gases effect on neuromuscular

Answer 16

Enhances activity of NMBs by all except N2O (no effect)

Question 17

N2O special effects compared to volatiles

Answer 17

Sympathetic stimulation
Pulm vasoconstriction (risk for RV failure)

Diffusion hypoxia
Decreases CMRO2
Highly solvable can diffuse into air spaces

Question 18

Gases toxicity

Answer 18

1) hepatic toxicity (halo> enf >iso>Des)
2) Nephro toxicity (methoxy>enf>Sevo)
3) CO production (baralyme>soda) and high temp
4) neurotoxicity

N2O toxicity

1) megaloblastic hematopoiesis (BM failure)
2) subacute combined degeneration of SC
3) immunosuppressant
4) teratogenic

Least hepatotoxic is Des

Question 19

Recommended exposure limit to gases over one hour-parts per million is

Answer 19

2 ppm for all volatiles and 25 ppm for N2O

Question 20

IV Anesthetics effusion (hypnosis, Analgesia, relaxation)

Propofol 
Etomidate
Barbiturates 
Benzodiazepines 
Ketamine

Answer 20

Hypnosis/amnesia -> achieved by all (except ketamine cause dissociative)

Analgesia -> only ketamine

Relaxation-> all except (myoclonus by Etomidate and ketamine cause catalepsy)

Question 21

IV anesthetics targets (GABA, glycine, Ach, NMDA)

Propofol 
Etomidate 
Barbiturates 
Benzodiazepines 
Ketamine

Answer 21

All potentiates GABA (except ketamine dose not)

3 has NMDA inhibition -> Ketamine, propofol, barbiturates

Propofol only inhibits glycine and ACh

Question 22

Barbiturates (methohextol & thiopental)

MOA
Onset
Effects

Answer 22

Onset: 10-30 sec

(+) GABA Cl- current and (-) NMDA (hypnotic, amnestic, non analgesic)

Myocardial depressant and (-) SNS
RS depressant
Barbiturates coma (decreases CMRO2)
Induces ALA synthetase (avoided in porphyria)
Intra-arterial vasoconstriction or crystallization

Question 23

Benzodiazepines

MoA
Effect

Answer 23

(+) GABA
Hypnotic, anxiolytics, amnestic, non-analgesic

Tolerance and withdrawal
Minimal CVS effect
RS depressant esp with opioids

Reversed by flumanzil

Question 24

Etomidate

MoA
Effects

Answer 24

(+) GABA
Hypnotic, amnestic

Minimal HD & RS effect
(-) 17 alpha hydroxylase (adrenal suppression)
Nausea/vomiting
Thrombophlebitis/ pain on injection 
Myoclonus

Question 25

Ketamine

MoA
Effects

Answer 25

(-) NMDA
Hypnotic, amnestic and Analgesic

Dissociative effect
Vivid nightmares 
Cateplexy 
Release endogenous catacholamine ( increases BP and HR except in catecholamine depleted patients)
Bronchodilation 
Increases ICP & IOP

Avoided in IHD, cranial mass or globe injuries

Question 26

Propofol

Answer 26

(+) GABA, (-) glycine, Ach, and NMDA
Hypnotic and amnestic

No tolerance
CVS & RS depressant (the most out of all IV anesthetics)

Lipid emulsion (egg allergy)
Pancreatitis/hypertriglycemia
Propofol infusion syndrome (4mg/kg/hr > 48hrs, refractory bradycardia, met acidosis, rhabdomyolysis, fatty liver)

Question 27

Dexmetadomidine

Answer 27

Selective beta-2 agonist

Sedation, hypnosis & anxiolytics (effect on locus caeruleus), sympatholysis.

Reduces opioids requirement

Increases RR and decreases Tv but preserves CO2 responsiveness

Bradycardia and decreases BP, CO, SVR and Contractility (hypertension with bolus due to peripheral vasoconstriction followed by hypotension)

Question 28

Opioid receptors

Answer 28

Analgesia by all except sigma

Euphoria-> Mu1 (delta and sigma cause dysphoria)

Hypoventilation, constipation, dependence ->
Mu2 & delta

Urinary retention-> Mu1 & delta (kappa causes diuresis)

Bradycardia-> Mu1
Tachycardia -> sigma

• Delta causes everything except no arrhythmias and cause dysphoria
• Kappa only analgesia and has diuresis
• Sigma is non analgesic, cause dysphoria & tachycardia
• Mu1: analgesia, retention and bradycardia
• Mu2: analgesia, hypoventilation, dependence, constipation

Question 29

The 2 no tolerance develops from opioids are

Answer 29

Miosis and constipation

Question 30

Neuroaxial opioids work by …

Answer 30

Mu receptors in substantia gelatinosa inhibits release of substance P

More lipoPhilic absorbed quickly but has shorter and less potent (siphoned off into epidural fat)

Hydrophilic (morphine) have spinal site of action
More hydrophobic (sufentanil) acts supraspinally
Intermediate hydrophobicity (fentanyl) acts spinally with bolus, supraspinally with infusion

Question 31

Methadone

Answer 31

Mu (+) and (-) NMDA
Lipid soluble with long t1/2 (15-60 hr)

Large t1/2 variability due to pharmacogentic CYP difference

Question 32

Meperidine

Answer 32

Atropine-like structure -vagolytic effect

Local anesthetic effects

Seretonin syndrome if given to patients who takes MAOI or SSRI

Question 33

Local anesthetics are ester and amides, which one has allergic potential

MoA

Answer 33

They work by binding to intracellular Na channels
Sensitive to small less myelinated and slow conduction current (ANS> sensory>motor)

Ester

• metabolized by plasma esterases
• PABA derivatives

Amides
- hepatic metabolized

Question 34

Local anesthetics onset depends on… and potency … where duration …

Answer 34

PKa -> onset (the lower pKa the faster, except chlorprocaine has high pKa but the most fastest due to given high concentration)

Hydrophobicity -> potency (the more hydrophobic the more potent which they are the longer action locals, tetra/bupi/ropi/etidocaine)

Protein binding-> duration (long acting locals has most protein binding)

Question 35

Side effects of locals

1) LAST
2) cauda equine
3) TNS
4) N/V
5) cardio toxicity
6) Arachoniditis

Answer 35

LAST
- Bupi/Ropi/ procaine > 3mg/kg
- Lido/mepivacaine >4.5 mg/kg (7 +epi)
Others higher doses
- chlorprocaine/Tetracaine > 12 mg/kg
- prilocaine > 8 mg/kg

IV>IC>Paravertebral >Epidural >Brachial>spinal>fem/sciatic>SQ

Cauda equina

• prolonged pain,paralysis, sensory changes
• following high concentration of local

TNS

• pain only in buttocks, thighs and legs
• associated with lithotomy, knee scopes.
• within 24 hrs - 7 days
• no bowel or bladder involvement despite its name
• ttx with NSAIDs
• lidocaine (most) procaine

N/v -> from procaine
Arachoniditis -> chlorprocaine from EDTA
Cardio toxicity -> bupi (but has sensory> motor block and more potent than ropi)

Question 36

Methemoglobinemia induces locals are

Answer 36

Procaine
Benzocaine
Prilocaine

Question 37

EMLA creams

Answer 37

Has 2.5% lido + 2.5 prolilocaine

C/I with amide sensitive patients

Monitor ECG if on amiodarone or sotalol

Additive effect with Bretylium or dofetilide

Question 38

Histamine release NMBs

Answer 38

Benzylisoquinolinum (-uriusm) except cisatracurium

Question 39

Dibucaine fest

Answer 39

Normal >80 for 5 min

40-60 -> heterozygous: 30 min

<20 -> homozygous: >4 hrs

Question 40

Special facts about NMBs

Answer 40

Pancuronium

• has muscarinic effec leads to small increase CO & HR
• longest action

Mivacurium-> shortest action

Intermediated actions
- vacronium -> has active metabolite 3-desacetylvecuronium

• atracurium & cisatracurium
  — metabolized by plasma esterases (Hoffman depredation)
  —- active metabolite (lananosine) decreases seizure threshold
  —- only atracurium releases histamine

Question 41

A 23-year-old patient presents to labor and delivery and receives epidural anesthesia. Where do epidurally-administered opioids primarily exert their effects?

A. At peripheral opioid receptors, after systemic absorption
B. In the substantia gelatinosa of the spinal cord, after diffusion across the dura
C. On opioid receptors in the dura
D. In the brainstem, after diffusion into the cerebrospinal fluid
E. On opioid receptors in the nerve roots

Answer 41

Although there is some systemic absorption of opioids after epidural administration, the amount absorbed varies according to individual drug lipophilicity. The primary mechanism by which epidural opioids exert their effects is through binding of opioid receptors in the substantia gelatinosa of the spinal cord, after diffusion across the dura. The dura itself does not have opioid receptors, nor do the opioids exert effects at nerve roots. While local anesthetics may affect brainstem function, such as in the case of a “total spinal,” opioids do not primarily bind there.

Question 42

A 40-year-old patient in preop clinic is optimized for her hypertension prior to surgery. Which one of the following options is an adverse effect of hydrochlorothiazide?

A. Pancreatitis
B. Hyperkalemia
C. Hypocalcemia
D. Pulmonary edema
E. Pulmonary fibrosis

Answer 42

Hydrochlorothiazide is a thiazide diuretic that works on the distal convoluted tubule to block the NaCl cotransport mechanism leading to urinary dilution. Side effects of hydrochlorothiazide include pancreatitis, jaundice, diarrhea, aplastic anemia, hypokalemia, and hypercalcemia. Hydrochlorothiazide is not known to cause pulmonary dysfunction. Thus A is the best answer.

Question 43

A 45-year-old patient presents to preop clinic and inquires about scopolamine as a proactive measure to reduce PONV. Which one of the following is a possible side effect of scopolamine administration?

A. Blurred vision
B. Muscle weakness
C. QT interval prolongation
D. Pruritus
E. Hyperglycemia

Answer 43

Scopolamine is a centrally acting anticholinergic that similar to atropine. Its antiemetic properties are well established for the prevention of postoperative nausea and vomiting (PONV), as well as motion-induced nausea and vomiting. Scopolamine is associated with an increased incidence of side effects, which include blurred vision, dizziness, dry mouth, and agitation.
Droperidol is a highly potent D2 antagonist with well accepted antiemetic properties. The U.S. Food and Drug Administration issued a black box warning for droperidol after receiving several reports of severe arrhythmias and deaths in association with its use. The drug is now contraindicated in patients with known or suspected QT prolongation. Scopolamine is not known to cause pruritus or hyperglycemia.

Question 44

A 65-year-old woman with a large soft tissue sarcoma of her back is scheduled for an extensive sarcoma excision and reconstruction. The patient is very concerned about her postoperative pain control. An intraoperative lidocaine infusion is planned. Which of the following is correct regarding an intraoperative lidocaine infusion?

A. The clinical effects of the lidocaine infusion are terminated at the end of the infusion
B. The benefits of perioperative lidocaine infusion include reduction in pain but not in ileus duration and length of hospital stay
C. The benefits of perioperative lidocaine infusion include reduction in opioid requirements but not in nausea
D. The customary perioperative lidocaine infusion dose ranges from 1.5-3 mg/kg/hr (after a bolus of 0-1.5 mg/kg)
E. The mechanism of intraoperative lidocaine infusion is primarily by sodium channel blockade

Answer 44

Concern about opioid risks in the postoperative period has lead to an increased interest in the use of nonopioid analgesic adjuncts, as is intravenous lidocaine.
Option A is incorrect as the benefits of lidocaine infusion persist long after the drug is metabolized to nonbiologically active concentrations. Its clinical effects exceed the duration of the infusion by more than 8.5 hours, which is 5.5 times the half-life of the compound drug.
Options B and C are incorrect as the benefits of perioperative lidocaine infusion include reductions in pain, nausea, ileus duration, opioid requirements and length of hospital stay.
Option D is correct as the usual perioperative lidocaine infusion dose ranges from 1.5-3 mg/kg/hr (after a bolus of 0-1.5 mg/kg).
Option E is incorrect as the mechanism of intraoperative lidocaine infusion is likely interference with other molecular targets, such as those involved in inflammatory signaling, and not primarily a sodium channel blockade.

Question 45

A patient with a history of opiate abuse is under general anesthesia and ketamine is used as an adjunctive analgesic. Ketamine has which one of the following effects?

A. Increased CBF, increased intraocular pressure, increased peripheral resistance, and bronchodilation
B. Increased CBF, decreased intraocular pressure, increased peripheral resistance, and bronchodilation
C. Increased CBF, increased intraocular pressure, increased peripheral resistance, and bronchoconstriction

Answer 45

Ketamine causes sympathetic stimulation and results in increases in heart rate, contractility, and peripheral resistance. Ketamine results in bronchodilation and minimal respiratory depression. It can be used in asthmatics, although it does increase airway secretions. Ketamine also leads to increases in CBF, ICP, and CMRO2, making it a poor choice in patients with head trauma unless other anesthetics are used concomitantly. Lastly, it leads to increases in intraocular pressure and nystagmus, which is an important consideration for patients undergoing eye surgery or trauma to the eye.

Question 46

An 86-year-old man diagnosed with hypertension and congestive heart failure comes to you at the clinic complaining of dizziness and syncope almost daily half an hour after breakfast. His lab profile is unremarkable and you document a reduction of systolic blood pressure of 25 mm Hg after the meal. Which of the following hormones plays a role in this condition?

A. Epinephrine and norepinephrine
B. Atrial natriuretic peptide
C. Neurotensin and kinins
D. Insulin and Octreotide
E. Glucagon and glucose-dependent insulinotropic peptide 1

Answer 46

The correct answer is neurotensin and kinins. The patient described in the question is a case of postprandial hypotension. Postprandial hypotension is a normal physiological phenomenon that occur in healthy individuals after meals. It’s always asymptomatic. However, it becomes symptomatic in elderly individuals, patients with poorly controlled blood pressure, heart failure, Parkinson’s disease, those on dialysis; and persons with autonomic dysfunction. The mechanism of hypotension in these cases is related to postprandial splanchnic hyperemia. After meal ingestion, more than 15% of blood volume is contained within the splanchnic vessels to aid digestion.
The blood flows to the left gastric and celiac as early as few minutes (10-20 minutes) after food ingestion. Then, it flows to the superior mesenteric arteries later and is prolonged to several hours. The pathophysiological mechanisms of postprandial hyperemia include CNS anticipation, mucosal metabolism, hyperosmolarity after nutrients absorption, and the action of vasoactive gastrointestinal hormones including cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin, substance P and kinins.

Question 47

A 23-year-old woman is scheduled for a diagnostic laparoscopy. Past medical history is non-significant. Her only medication is the oral contraceptive pill. During the procedure, rocuronium is used for muscle relaxation and sugammadex is administered as a reversal agent. Which of the following statements regarding sugammadex is correct?

A. Sugammadex reverses nonsteroidal neuromuscular blocking agents
B. Sugammadex is the preferred agent for patients with end stage renal failure
C. The patient must be advised that an additional non-hormonal method of contraception must be used for the next seven days
D. The dose of sugammadex, after spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation, is 16 mg/kg
E. If re-administration of a neuromuscular blocking agent is required 2 minutes after reversal with sugammadex, then vecuronium is the preferred agent

Answer 47

Sugammadex is a modified cyclodextrin and is the first selective relaxant binding agent available. It reverses the effects of non-depolarizing steroidal neuromuscular blocking drugs by binding to the free molecules of the muscle relaxant. As a result, there is a reduction in the concentration of the free muscle relaxant, leading to a rapid termination of the neuromuscular block.
Option A is incorrect as sugammadex is indicated for the reversal of the steroidal neuromuscular blocking drugs rocuronium and vecuronium, and not the non-steroidal neuromuscular blocking drugs.
Option B is incorrect as sugammadex is not recommended in patients with severe renal impairment.
Option C is correct as sugammadex may bind to progesterone and decrease effectiveness of hormonal contraceptives. Patients must be advised that an additional non-hormonal method of contraception must be used for the next 7 days.
Option D is incorrect as the recommended dose of sugammadex is 2 mg/kg, if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation. 16 mg/kg is recommended if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single dose of 1.2 mg/kg of rocuronium.
Option E is incorrect as a nonsteroidal neuromuscular blocking agent, such as cisatracurium, is preferrable used if re-administration of a neuromuscular blocking agent is required 2 minutes after reversal with sugammadex.

Question 48

How local anesthetics causes fetal toxicity

Answer 48

Local anesthetics tend to accumulate in the fetus due to its inherent lower pH compared to the mother, which ionizes the drugs and therefore, renders it unable to cross the placenta to get back to the mother. Even though the placental hydrophobicity a) and therefore its lipophilic nature let the local anesthetics cross in the first place, ion trapping is the main cause of the accumulation and toxicity of the drug.

Question 49

You’re evaluating a 72-year-old male patient with a right femoral shaft fracture. A surgical repair is scheduled for the following day. The patient’s past medical history is remarkable for hypertension treated with diltiazem. Following the initiation of analgesia, the patient develops tachycardia with hypotension. A repeat physical exam is remarkable for mydriasis. Which of the following medication is the most likely cause of this patient’s symptoms?

A. Morphine
B. Fentanyl
C. Meperidine
D. Hydromorphone

Answer 49

This case describes a patient with tachycardia, hypotension, and mydriasis following analgesia with opioids. Option C, meperidine (pethidine), is unique amongst the opioids for its anticholinergic effects. Unlike other opioids, meperidine causes tachycardia due to its structural similarity to atropine. It can also cause hypotension due to its histamine-releasing effect. Mydriasis is also explained by the atropine-like effect.
Other opioids, Options A, B, and D, would be expected to cause miosis due to their excitatory action on the Edinger-Westphal nucleus. As such, Option C is the correct answer.

Question 50

Neurotoxicity caused by Nitric oxide (NO) is due to which of the following?

A. Cerebral vasodilation
B. Increase in MABP
C. Increase in CBF
D. The formation of lethal free radicals

Answer 50

Nitric oxide (NO) plays several roles in the central nervous system as a messenger molecule. However, when generated in excess, NO can be neurotoxic. It has been postulated that neurotoxic actions of NO are mediated by peroxynitrite (ONOO-), the reaction product from NO and superoxide anion (D). In pathologic conditions, peroxynitrite and oxygen free radicals can be generated in excess of a cell antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological characteristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical and oxidant mediated insult.
NO causes cerebral vasodilation (A), increase in MABP (B) and increase in CBF (C). All of these actions are not associated with neurotoxicity.

SOURCE: Dawson, V. L., & Dawson, T. M. (1996, June). Nitric oxide neurotoxicity. Retrieved March 05, 2018, from https://www.ncbi.nlm.nih.gov/pubmed/8811421

Question 51

A 57-year-old man develops acute foot drop after lifting a heavy box and MRI reveals an L2-3 herniated disc. He is scheduled for emergent decompression in hopes of restoring his neurologic function. Somatosensory evoked potentials are to be used during the case. One hour into the procedure under total intravenous anesthesia (TIVA), the potentials are noted to be diminishing in spite of normal vital signs. Which medication will increase the amplitude of the somatosensory evoked potentials and possibly avoid the need for a wake up test?

A. Sevoflurane
B. Propofol
C. Rocuronium
D. Ketamine

Answer 51

D is correct because ketamine and etomidate increase the amplitude of SSEPs.
A is incorrect because all inhaled volatile anesthetics reduce the amplitude and increase the latency of somatosensory evoked potentials (SSEPs). Potent inhaled volatile agents must be kept less than 0.5 MAC. During motor evoked potentials, it’s best not to use them at all.
B is incorrect because propofol, although part of a total intravenous anesthetic, does not, by itself, increase the amplitude of SSEPs.
C is incorrect because rocuronium, a muscle relaxant, has no effect on the SSEPs and additionally, is not used when motor evoked potentials are monitored.