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PHARM Flashcards

1
Q

Which drugs can cause ototoxicity?

A

Ototoxicity and nephrotoxicity can be caused by:

  1. Aminoglycosides
  2. Vancomycin
  3. Loop diuretics
  4. Cisplatin (may respond to amifostine)
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2
Q

What type of G-protein coupled receptors are D2 receptors? Where are they found in the body?

A

D2 dopamine receptors are i-subtype G-protein coupled receptors that are found almost exclusively in the central nervous system.

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3
Q

What are the two fates of drugs that are inactivated by phase 1 metabolism?

A

Many drugs are inactivated following phase I metabolism. Following inactivation, there are two possible scenarios:

Renal excretion. If drugs become sufficiently polar post-phase I biotransformation, they will remain in urine and get excreted.

Phase II metabolism. Most inactivated drugs (following phase I metabolism) undergo further biotransformation before being cleared from the body.

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4
Q

Cocaine is mixed into an epinephrine solution and injected into the nasal mucosa to decrease bleeding. The reason for this mixture is?

A Cocaine decreases the reflex tachycardia from epinephrine

B Epinephrine’s acidic pH is increased by cocaine

C Cocaine decreases the hypertension caused by epinephrine

D Both cocaine and epinephrine have local anesthetic effects

E Cocaine potentiates the vasoconstrictive effect of epinephrine by inhibiting monoamine reuptake

A

Cocaine potentiates the vasoconstrictive effect of epinephrine by inhibiting monoamine reuptake

Answer Explanation

Cocaine, unlike any other local anesthetic, has vasoconstrictive actions. All other local anesthetics (lidocaine, tetracaine) have vasodilatory effects. The vasoconstrictive action of cocaine is used to limit bleeding in nasal mucosa. Cocaine functions by inhibiting the reuptake of monoamines into presynaptic terminals, thus potentiating the effect of monoamines. As such, cocaine causes vasoconstriction vis-à-vis potentiation of the effects of epinephrine. The local anesthetic effect of cocaine comes from the blockage of voltage-gated sodium channels, which is an effect that is independent of its effect on monoamine reuptake transporters. Currently, the only approved therapeutic use of cocaine in the clinic is as a local anesthetic and vasoconstrictive agent during otolaryngologic and opthalmologic surgeries.

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5
Q

Where do α2-adrenergic agonists act in the body? What physiologic effect(s) does this cause?

A

Activation of α2-receptors in the medulla results in decreased sympathetic tone.

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6
Q

Concurrent administration of furosemide with gentamicin increases the risk for which of the following side effects?

A SLE like syndrome

B Hyperkalemia

C Ototoxicity

D Photosensitivity

E Tendonitis

A

Ototoxicity

Answer Explanation

Aminoglycosides, loop diuretics, and cisplatin all have a risk of ototoxicity. In fact, concurrent administration of furosemide with gentamicin increases the risk of hearing loss.

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7
Q

Which 8 drugs should be avoided if a patient has a sulfa allergy?

A

The following sulfa drugs should be avoid in patients with a sulfa allergy:

Probenecid

Furosemide

Acetazolamide

Celecoxib

Thiazides

Sulfonamides

Sulfasalazine

Sulfonylureas

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8
Q

What three conditions are treated with amphetamine?

A

Amphetamine can be used to treat the following conditions:

Narcolepsy

ADHD

Obesity

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9
Q

What enzyme catalyzes the tyrosine to melanin reaction?

A

Other fates of tyrosine include:

Tyrosine to DOPA and finally melanin (key enzyme: tyrosinase)

Tyrosine to T3 and T4 (directly by iodination)

Tyrosine catabolism, producing acetoacetate and fumarate (proceeds via homogentisate intermediate)

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10
Q

What condition is timolol used to treat? How does it accomplish this?

A

In the treatment of open-angle glaucoma:

Timolol is the agent of choice for this condition; as a non-selective β-blocker, it decreases the secretion of aqueous humor by the ciliary epithelium.

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11
Q

What effect do surface area and vascularity have on the volume of distribution of a drug?

A

Surface area and vascularity of the affected area also influence the drug’s distribution, but this is not a property of the drug. Increased blood flow increases drug delivery, and increased surface area allows the drug to be absorbed more efficiently.

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12
Q

What is the mnemonic for the drugs that can cause gynecomastia?

A

The drugs that cause gynecomastia can be remembered with the mnemonic:

Some Drugs Create Really Awesome Knockers

The drugs include:

Spironolactone

Digitalis

Cimetidine

Risperidone

Alcohol

Ketoconazole

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13
Q

Name one clinical use for phentolamine.

A

Phentolamine is used to treat hypertensive crisis in patients on MAO inhibitors who have eaten tyramine-containing foods.

​Phentolamine can also be used to diagnose pheochromocytoma: patients with the tumor will show a greater than expected decrease in blood pressure upon treatment with phentolamine.

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14
Q

How does guanethidine interfere with the synthesis and release of norepinephrine?

A Inhibiting DOPA decarboxylase

B Inhibiting dopamine-β-hydroxylase

C Inhibiting tyrosine hydroxylase

D Preventing vesicle release of norepinephrine into synapse

E Preventing presynaptic reuptake

A

Preventing vesicle release of norepinephrine into synapse

Answer Explanation

Metyrosine inhibits tyrosine hydroxylase (this is the rate limiting step in catecholamine synthesis)

Reserpine inhibits the ATP/Mg2+ pump that sequesters neurotransmitters into storage vesicles in the presynaptic neuron. These unsequestered neurotransmitters are rapidly metabolized by monoamine oxidase, leading to a global reduction in catecholamines.

Guanethidine prevents vesicle release of NE into synapse.

Cocaine and TCAs prevent presynaptic neurotransmitter reuptake.

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15
Q

Name three pathologic conditions that might affect the Vd of a drug.

A

VD can be affected by a variety of factors, but three major pathologic conditions that affect VD are the following:

Liver disease

Kidney disease

Obesity

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16
Q

What physical signs are associated with carbon monoxide toxicity? What is the antidote?

A

The antidote for carbon monoxide is 100% oxygen or hyperbaric oxygen.

Symptoms associated with toxicity include:

Headache is the first symptom

Cherry red skin and mucous membranes

Confusion

​If the patient was exposed to fire and has almond breath, suspect cyanide.

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17
Q

What are five side effects of Bethanechol?

A

Bethanechol has the following side effects.

Bradycardia

Hypotension

Sweating

Salivation

Diarrhea

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18
Q

What symptoms are associated with isoniazid toxicity?

A

The antidote for isoniazid toxicity is pyridoxine (vitamin B6).

Symptoms associated with isoniazid toxicity include:

Confusion

Peripheral neuropathy

Hepatotoxicity

Seizures

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19
Q

What is an example of a receptor that behaves according to spare receptor theory?

A

In spare receptor theory, a second messenger amplification system could lead to a maximal response despite only a few extracellular sites being activated. For example, G-coupled receptors.

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20
Q

How does noncompetitive inhibition affect Km and Vmax?

A

In these reactions, the enzyme cannot overcome inhibition by increasing substrate concentration. Kmstays constant while Vmax decreases.

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21
Q

What is the source of scombroid poisoning?

A

Scombroid poisoning occurs after ingestion of Scombridae (tuna, mackerel).

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22
Q

What clinical applications can cocaine be used for?

A

Cocaine can be used to cause local anesthesia and vasoconstriction.

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23
Q

How does the effect of atropine on heart rate vary with dose?

A

Atropine can be used in the treatment of bradycardia, asystole, and heart block. At high or toxic doses of atropine, heart rate increases (note that at low doses, the effect is bradycardia secondary to atropine-induced acetylcholine release from inhibitory neurons).
These effects are due to the inhibition of parasympathetic tone on the heart, leading to an increase in heart rate.

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24
Q

What are the 2 substrates used to synthesize ACh?

A

Ch is synthesized in the presynaptic nerve terminal via the combination of choline with Acetyl CoA.

25
Q

How do partial agonists compare with full agonists in terms of efficacy and potency?

A

Partial Agonist have a lower efficacy at all doses relative to a full agonists. Potency is an independent factor (can have more, less, or equal potency compared to the original agonist).

26
Q

What are two differences that distinguish indirect sympathomimetics from direct sympathomimetics?

A

Indirect sympathomimetics have two differences that distinguish them from direct sympathomimetics:

Indirect sympathomimetics can generallypenetrate the blood-brain barrier and act centrally.

Indirect sympathomimetics are usually non-specific and generally activate both α and β adrenergic receptors.

27
Q

Generally speaking, what is an irreversible competitive inhibitor?

A

Irreversible competitive inhibitors are substances thatresemble the substrate and bind to the active site, but cannot be overcome by increasing the substrate concentration.

28
Q

For a given drug or pharmacologic agonist, what does “efficacy” mean? On which axis of the dose-response curve is it found?

A

Efficacy (Emax) is defined as the maximal response produced by the drug/agonist. On a dose-response curve for a given drug, efficacy is represented by the y axis.

29
Q

How is the loading dose of a drug calculated?

A

The loading dose of a drug is a function of target plasma concentration at steady state (Cp), volume of distribution (Vd), and bioavailability (F) and is calculated as follows:

(Cp* Vd)/F

30
Q

You are a physician-scientist in charge of investigating a certain Drug X. During a phase I clinical trial, you find that co-administration of a commonly prescribed Drug Y causes the dose-response curve of Drug X to shift to the right. In this circumstance, what is happening to the potency of Drug X?

A

The administration of a second agent can affect the potency of a drug or agonist, which appear as horizontal shifts of the dose-response curve:

Left shift = Increased potency

Right shift = Decreased potency

31
Q

Kinetically, how are most drugs eliminated from the body?

A

Most drugs eliminated by first-order elimination

32
Q

What enzyme catalyzes the formation of ACh?

A

The enzyme choline acetyltransferase (ChAT) catalyzes this step. Newly formed ACh is then packaged into presynaptic vesicles via the ACh transporter.

33
Q

What is the mechanism of action for cocaine?

A

Cocaine acts by inhibiting catecholamine reuptake transporters.

34
Q

Which types of G protein coupled receptor transmits signals from D1 receptors?

A

Alternatively, use the mnemonic: “QISS and QIQ till you’re SIQ of SQS”
α1 – Q
α2 – I
β1 – S
β2 – S

M1 – Q
M2 – I
M3 – Q

D1 – S
D2 – I
H1 – Q

H2 – S
V1 – Q
V2 – S

35
Q

Which α-subtype receptor does phenylephrine preferentially activate?

A

Phenylephrine acts as an agonist on both α1 and α2 receptors, but has stronger preference for the α1 receptor. (α1>α2)

36
Q

What is an over the counter herbal supplement that causes selective alpha 2 blockade?

A

Another selective α2 blocker is yohimbine, which is an over the counter herbal supplement. Yohimbine is a selective α2 receptor antagonist which has been used for the treatment of erectile dysfunction, though its efficacy has never been validated. Small studies suggest that it may be useful in the treatment of postural hypotension as blockade of α2 receptors by yohimbine would result in increased adrenergic tone.

37
Q

What are 4 different ligand-gated ion channels?

A

Ligand-gated ion channels are activated by binding of a biochemical messenger, such as a neurotransmitter. There are four types of ligand-gated ion channels that are important to remember:

Nicotinic acetylcholine receptors

GABAA receptors, which are ionotropic receptor linked to chloride channels. GABAB receptors aremetabotropic G-protein coupled receptors linked to potassium channels.

Ionotropic glutamate receptors

Glycine receptors

38
Q

Fill in the blanks for the following equation relating clearance to the volume of distribution of a drug: CL = (_______ x Vd) / (_____).

A

Clearance is related to the volume of distribution by the following equation:

CL = ln(2) (VD/ t1/2)
This is equal to:

CL=(0.693 VD)/t1/2

39
Q

What is the role of phenoxybenzamine in the surgical management of pheochromocytoma?

A

Phenoxybenzamine is used preoperatively to prevent acatecholamine/hypertensive crisis in patients with pheochromocytoma (this is done before beta blockade). It has both a slower onset and longer duration of action when compared to other α blockers, which minimizes the likelihood of severe hypertension during surgical removal of the pheochromocytoma.

40
Q

What subtype of G-protein coupled receptors are alpha-2 adrenoceptors? What is their role?

A

α2 adrenoceptors are i-subtype (inhibitory) G-protein coupled receptors that serve to suppress sympathetic outflow.

41
Q

How does dopamine increase cardiac output at low-medium doses?

A

At low-medium doses, dopamine increases cardiac output by acting on β receptors to cause both inotropic and chronotropic stimulation of the heart.

42
Q

What are ten inhibitors of CYP450 enzymes?

A

There are ten inhibitors of CYP450 enzymes:

Acute alcohol abuse

Ritonavir

Amiodarone

Cimetidine

Ketoconazole

Sulfonamides

Isoniazid

Valproic acid

Grapefruit juice

Quinidine

Macrolides (but NOT azithromycin)

Mnemonic: AAA RACKS In eVery GQ Magazine.

43
Q

What do inhibitors of CYP450 do? What does this lead to?

A

Inhibitors of CYP450 prevent the enzymes from metabolizing their substrates. This results in an increased plasma concentration of untransformed CYP450 targeted drugs.

44
Q

What are four commonly used drugs/drug categories that are metabolized by CYP450?

A

Four commonly used drugs that CYP450 enzymes metabolize (meaning drugs that are substrates) include:

Anti-epileptic agents

Theophylline

Warfarin

Oral contraceptive pills

Mnemonic: Always Think When Outdoors

45
Q

Is albuterol used to treat acute or chronic asthma?

A

Albuterol is used to treat acute asthma

46
Q

What is the function of the Lineweaver-Burk plot? What does the slope of the plot represent?

A

The Lineweaver-Burk plot (double reciprocal plot) is alinear transformation of the Michaelis-Menten equation. Particularly useful for evaluating mechanism of inhibition. Km and Vmax can be obtained from the linear regression.

47
Q

Define the pharmacokinetic term “steady state.”

A

Steady state (Css) refers to when a drug is continuously infused, it will reach a concentration at which point the rate of input and the rate of elimination balance each other.

48
Q

What are two known effects of M1 receptor activation?

A

M1 receptor activation has the following effects:

  1. Increased gastric acid secretion
  2. Increased salivary secretion
  3. The role of M1 activation in the CNS is currently unknown.
49
Q

How do organophosphates cause increased cholinergic stimulation?

A

Organophosphates bind covalently to cholinesterases, which results in enzymatic inactivation. This results in decreased degradation of acetylcholine, and a consequent increase in cholinergic stimulation.

50
Q

What is the antidote for aspirin toxicity?

A

The antidote for aspirin (ASA) toxicity is HCO3- to treat acidosis and dialysis.

51
Q

What is the antidote for anticholinergic toxicity?

A

The antidote for anticholinergic toxicity is physostigmine, which can cross the blood brain barrier to treat delirium.

52
Q

How do you calculate a drug’s volume of distribution?

A

The volume of distribution (VD) of a drug is a ratio of the total amount of drug in body (D) to the plasma drug concentration (C0), which is represented by the equation:
V_D=D/C_0

53
Q

Which 6 drugs can cause photosensitivity?

A

Photosensitivity can be caused by:

Sulfonamides

Amiodarone

Tetracycline

Isotretinoin

5-Fluorouracil

Simeprevir

Demeclocycline

54
Q

Mirtazapine belongs to which drug class?

A

Selective α2 blockade is accomplished withmirtazapine. This drug also antagonizes 5HT2 and 5HT3.

55
Q

Pharmacodynamically speaking, if a cell increases its expression of receptors for a certain ligand, what happens to the cell’s sensitivity for that ligand?

A

Since drug effect is a direct result from the activity of downstream effectors (a cascade), a cell can increase its expression of surface receptors to produce a more sensitive response.

If you have many more receptors, then you need less drug to bind the same amount of receptors and produce the same downstream effect.

56
Q

What is the rate of metabolism in first-order elimination?

A

In first-order elimination, there is a constant fraction of drug eliminated per unit of time.

Drug plasma concentration decreases exponentiallywith increased time.

Most drugs eliminated by first-order elimination.

57
Q

What subtype of G-protein coupled receptors are M1 receptors? Where are they found in the body?

A

M1 receptors are q-subtype G-protein coupled receptors which are found in the central nervous system as well as in the enteric nervous system.

58
Q

Which anticholinergic agents can be used to treat asthma and COPD?

A

Ipratropium and tiotropium are two agents used to treat asthma and COPD by counteracting parasympathetic bronchoconstriction.

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