Ramtin Yeganeh
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4th Final Quiz on Pharma MCQs- 4th Year- Corrected, created by Ramtin Yeganeh on 08/01/2019.

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Pharma MCQs- 4th Year- Corrected

Question 1 of 108

1

The main routes of enteral administration of drugs are:

Select one or more of the following:

  • oral

  • by injection

  • rectal

  • per mucosa

Explanation

Question 2 of 108

1

Advantages of the oral route of drug administration are:

Select one or more of the following:

  • easily self-administered

  • toxicity and overdose may be overcome with antidotes

  • drugs avoid first-pass metabolism

  • drugs go directly into the systemic circulation

Explanation

Question 3 of 108

1

Advantages of the rectal route of drug administration are:

Select one or more of the following:

  • suitable for vomiting patients

  • suitable for children

  • suitable for unconscious patients

  • a way to avoid first-pass metabolism

Explanation

Question 4 of 108

1

Disadvantages of intravenous drug administration are:

Select one or more of the following:

  • a trained staff is required

  • risk of bacterial contamination at the site of injection

  • it is painful and stressful for the patient

  • drugs undergo first-pass metabolism in the liver

Explanation

Question 5 of 108

1

Point out the correct statements for intravenous drug administration:

Select one or more of the following:

  • aqueous solutions can be administered i.v.

  • oil solutions can be administered i.v.

  • has the highest bioavailability

  • used for treatment of life-threatening conditions

Explanation

Question 6 of 108

1

The subject of pharmacokinetics is:

Select one or more of the following:

  • drug absorption and distribution

  • drug biotransformation

  • drug elimination

  • drug biological activity

Explanation

Question 7 of 108

1

Point out the correct statements for passive diffusion:

Select one or more of the following:

  • does not require energy

  • requires energy

  • involves a carrier

  • drugs move from high to lower concentration

Explanation

Question 8 of 108

1

A drug-weak acid will be absorbed

Select one or more of the following:

  • in a medium with low pH

  • in a medium with high pH

  • in the stomach

  • in the intestine

Explanation

Question 9 of 108

1

The diffusion of Iipid soluble drugs

Select one or more of the following:

  • depends on the charge of the drug molecule

  • does not depend on the charge of the drug molecule

  • is penetration through aqueous channels or pores

  • is penetration through the biological membranes

Explanation

Question 10 of 108

1

A drug-weak base will be absorbed

Select one or more of the following:

  • in a medium with low pH

  • in a medium with high pH

  • in the stomach

  • in the intestine

Explanation

Question 11 of 108

1

Point out the correct statements for active drug transport

Select one or more of the following:

  • it is energy - dependent

  • it is not energy - dependent

  • requires carriers

  • does not require carriers

Explanation

Question 12 of 108

1

Point out the correct statement for drugs bound to plasma proteins

Select one or more of the following:

  • bound drugs are pharmacologically active

  • only the unbound drugs can act on target sites in the tissues

  • only the bound drugs are available to the process of elimination

  • drugs may displace each other from the binding proteins

Explanation

Question 13 of 108

1

Drug metabolism may

Select one or more of the following:

  • increase a drug’s pharmacological activity

  • decrease a drug’s pharmacological activity

  • change the pharmacological effects of a drug

  • change the toxicity of a drug

Explanation

Question 14 of 108

1

First phase liver metabolism reactions include

Select one or more of the following:

  • acetylation

  • conjugation

  • reduction

  • oxidation

Explanation

Question 15 of 108

1

Second phase liver metabolism reactions include

Select one or more of the following:

  • acetylation

  • conjugation

  • reduction

  • oxidation

Explanation

Question 16 of 108

1

Phase 1 of drug metabolism

Select one or more of the following:

  • may or may not involve cytochrome P450 system

  • phase 1 reactions convert Iipophilic molecules to more polar molecules

  • includes alcohol dehydrogenation, amine oxidation, hydrolysis

  • consists of conjugation reactions

Explanation

Question 17 of 108

1

Renal excretion of a drug will be reduced if

Select one or more of the following:

  • the drug is a weak acid and the urine is alkaline

  • the drug is a weak acid and the urine is acidic

  • the drug is a weak base and the urine is alkaline

  • the drug is a barbiturate and the urine is alkaline

Explanation

Question 18 of 108

1

Drug pharmacodynamics includes

Select one or more of the following:

  • drug effects

  • mechanisms of drug action

  • drug elimination

  • how the organism changes drugs

Explanation

Question 19 of 108

1

The changes that occur due to the interaction between drug molecules and organism structures are called

Select one or more of the following:

  • drug effect

  • drug action

  • adverse drug reaction

  • placebo effect

Explanation

Question 20 of 108

1

The organism response as a result of the changes that have occurred due to its interaction with the drug is called

Select one or more of the following:

  • drug action

  • drug effect

  • adverse drug reaction

  • placebo effect

Explanation

Question 21 of 108

1

What is characteristic for a drug receptor

Select one or more of the following:

  • induces (generates) a change in organism functions

  • has selectivity

  • has sensitivity

  • has specificity

Explanation

Question 22 of 108

1

Agonists are ligands which

Select one or more of the following:

  • have affinity

  • block receptors

  • have intrinsic activity

  • bind to the receptor

Explanation

Question 23 of 108

1

Antagonists are ligands which

Select one or more of the following:

  • have strong affinity

  • have intrinsic activity

  • block the receptor

  • do not have intrinsic activity

Explanation

Question 24 of 108

1

Therapeutic margin is the

Select one or more of the following:

  • difference between minimal toxic and minimal therapeutic doses

  • ratio between minimal toxic and minimal therapeutic doses

  • difference between mean lethal and mean effective doses

  • ratio between lethal and mean effective doses

Explanation

Question 25 of 108

1

Drugs’ therapeutic index is the:

Select one or more of the following:

  • difference between minimal toxic and minimal therapeutic doses

  • ratio between minimal toxic and minimal therapeutic doses

  • difference between mean lethal and mean effective doses

  • ratio between mean lethal and mean effective doses

Explanation

Question 26 of 108

1

Types of drug interaction are:

Select one or more of the following:

  • synergy

  • antagonism

  • synergy/antagonism

  • chemical antagonism (formation of complexes)

Explanation

Question 27 of 108

1

Potentiation can be observed during the concomitant use of:

Select one or more of the following:

  • Fentanyl and Droperidol

  • Heparin and Protamine

  • Amoxicillin and Clavulanic acid

  • Diazepam and Flumazenil

Explanation

Question 28 of 108

1

Full competitive antagonist of opioid receptors, administered in acute opioid intoxication is:

Select one or more of the following:

  • Allylnormorphine

  • Methadone

  • Naloxone

  • Flumazenil

Explanation

Question 29 of 108

1

Chemical antagonism or complex formation can be observed in:

Select one or more of the following:

  • Morphine and Naloxone

  • Diazepam and Flumazenil

  • Epinephrine and Histamine

  • Iron preparation and Deferroxamine

Explanation

Question 30 of 108

1

Which of the following are enzyme inducers:

Select one or more of the following:

  • Phenytoin

  • Phenobarbital

  • Metamizol

  • Metronidazole

Explanation

Question 31 of 108

1

Multiple drug administration could lead to:

Select one or more of the following:

  • drug tolerance

  • drug dependence

  • drug accumulation

  • allergic reactions

Explanation

Question 32 of 108

1

Drug addiction/dependence involves:

Select one or more of the following:

  • drug tolerance

  • physical dependence

  • psychological dependence

  • allergy

Explanation

Question 33 of 108

1

Antiseptics are used for:

Select one or more of the following:

  • decontamination of laundry and sanitary facilities

  • decontamination of skin and mucous membranes

  • internal administration

  • treatment of fever

Explanation

Question 34 of 108

1

Disinfectants are used for decontamination of:

Select one or more of the following:

  • urine, faeces and other

  • mouth

  • instruments

  • clothing and underwear

Explanation

Question 35 of 108

1

Antiseptics and disinfectants are:

Select one or more of the following:

  • detergents

  • barbiturates

  • oxidizing agents and halogen derivatives

  • phenols

Explanation

Question 36 of 108

1

Mechanism of action of sulfonamide is:

Select one or more of the following:

  • they are synthetic analogues of p-aminobenzoic acid (PABA) and complete with it for the enzyme dihydropteroate synthetase

  • they increase the permeability of the bacterial cell membrane

  • they inhibit bacterial wall synthesis

  • they inhibit the synthesis of bacterial dihydrofolic acid

Explanation

Question 37 of 108

1

For non-combined sulfanamides is true:

Select one or more of the following:

  • have broad antibacteriai spectrum

  • have narrow antibacterial spectrum

  • they are bactericidal

  • they are bacteriostatic

Explanation

Question 38 of 108

1

Combined sulfonamides are:

Select one or more of the following:

  • bacteriostatic drugs

  • bactericidal drugs

  • antiviral drugs

  • narrow spectrum antimicrobial drugs

Explanation

Question 39 of 108

1

Fluoroquinoiones are:

Select one or more of the following:

  • Gentamycin

  • Moxifloxacin

  • Ciprofloxacin

  • Levofloxacin

Explanation

Question 40 of 108

1

Mechanism of action of quinolones is:

Select one or more of the following:

  • inhibition of protein synthesis

  • inhibition of cell wall synthesis

  • inhibition of topoisomerase II and IV

  • inhibition of DNA transcription and replication

Explanation

Question 41 of 108

1

Fluoroquinolones have:

Select one or more of the following:

  • broad antibacterial spectrum

  • narrow antibacterial spectrum

  • bacteriostatic effect

  • bactericidal effect

Explanation

Question 42 of 108

1

Adverse drug reactions of fluoroquinolones are:

Select one or more of the following:

  • articular cartilage erosion (arthropathy)

  • hypertension

  • seizures in patients with epilepsy

  • prolongation of QT interval

Explanation

Question 43 of 108

1

Antimicrobials that inhibit bacterial cell wall synthesis are:

Select one or more of the following:

  • penicillins

  • cephalosporins

  • monobactams

  • tetracyclines

Explanation

Question 44 of 108

1

Tetracyclines

Select one or more of the following:

  • are bactericidal

  • are bacterostatic

  • accumulate in tissues- in bones and teeth

  • are effective against rickettsiae, mycoplasma, chlamydia

Explanation

Question 45 of 108

1

Macrolide antibiotics are:

Select one or more of the following:

  • Azithromycin (Azatril)

  • Roxithromycin (Rulid)

  • Clarithroomycin (Klacid)

  • Gentamycin

Explanation

Question 46 of 108

1

Macrolides are:

Select one or more of the following:

  • bactericidal

  • bacteriostatic

  • inhibitors of methylxanthines’ metabolism

  • effective against mycoplasmas, Legionella, Chlamydia

Explanation

Question 47 of 108

1

Adverse drug reactions of macrolides include:

Select one or more of the following:

  • gastrointestinal disturbances

  • allergy

  • hepatotoxicity

  • nephrotoxicity

Explanation

Question 48 of 108

1

Beta-lactam antibiotics are

Select one or more of the following:

  • penicillins

  • cephalosporins

  • monobactams

  • carbapenems

Explanation

Question 49 of 108

1

Adverse drug reactions of penicillins are:

Select one or more of the following:

  • allergic reactions

  • hepatotoxicity

  • anaphylactic shock

  • disbactenosrs (for orally administered broad-spectrum penicillins)

Explanation

Question 50 of 108

1

Cephalosporins 1st generation are:

Select one or more of the following:

  • More effective against Gram (+) microorganisms

  • Cefalexin and Cefazolin

  • Bacteriostatic

  • Some agents are nephrotoxic

Explanation

Question 51 of 108

1

Cephalosporins 3rd generation are:

Select one or more of the following:

  • Cefetamet and Ceftriaxon

  • Cefaclor and Cefamandol

  • More effective against Gram (-) microorganisms

  • Used for treatment of life-threatening infections

Explanation

Question 52 of 108

1

Aminoglycoside antibiotics are:

Select one or more of the following:

  • Gentamaicin

  • Amoxiclav

  • Amikacin

  • Tobramycin

Explanation

Question 53 of 108

1

The correct statements of aminoglycoside antibiotics are:

Select one or more of the following:

  • they block protein synthesis and are bactericidal

  • they accumulate in soft tissues and bones

  • they are administrated orally for treatment of urinary infections

  • they are effective against Gram (-) microorganisms

Explanation

Question 54 of 108

1

Adverse drug reactions of aminoglycosides are:

Select one or more of the following:

  • nephrotoxicity

  • ototoxicity

  • myelotoxlcity

  • hepatotoxiclty

Explanation

Question 55 of 108

1

Azoles

Select one or more of the following:

  • are fungistatic

  • inhibit cell wall synthesis

  • inhibit ergosterol synthesis

  • inhibit hepatic CYP450 enzymes

Explanation

Question 56 of 108

1

ADRs of azole antifungals are:

Select one or more of the following:

  • hepatotoxicity

  • endocrine disorders

  • nephrotoxicity

  • nausea, vomiting

Explanation

Question 57 of 108

1

Point the correct statements for Nystatin

Select one or more of the following:

  • has fungistatic activity

  • causes gastrointestinal disturbances

  • is effective against Trichomonas vaginalis

  • is effective against Candida species

Explanation

Question 58 of 108

1

Point out the correct statements for Aciclovir

Select one or more of the following:

  • it inhibits viral DNA polymerase

  • it is used for treatment of herpes virus infections

  • it inhibits neuraminidase enzyme

  • can be applied topically, orally or intravenously

Explanation

Question 59 of 108

1

Mechanism of action of Oseltamivir (Tamiflu) is

Select one or more of the following:

  • interference with the function of the viral M2 protein

  • inhibition of specific neuraminidase enzyme

  • inhibition of reverse transcriptases

  • inhibition of proteases

Explanation

Question 60 of 108

1

Mechanism of action of Rifampicin (Rifampin) is

Select one or more of the following:

  • inhibition of cell wall synthesis

  • inhibition of 50 S ribosomal subunit

  • inhibition of DNA-dependent RNA polymerase

  • increased cell membrane permeability

Explanation

Question 61 of 108

1

ADRs of Rifampicin (Rifampin) are:

Select one or more of the following:

  • heart failure

  • orange-red color of urine and other secretions

  • hepatotoxicity

  • hypoglycaemia

Explanation

Question 62 of 108

1

What are the effects of benzodiazepines?

Select one or more of the following:

  • hypnotic effect

  • anxiolytic effect

  • muscle-relaxing effect

  • anticonvulsant effect

Explanation

Question 63 of 108

1

How do benzodiazepines exert their effects?

Select one or more of the following:

  • they enhance the effectiveness of GABA

  • they inhibit the phosphodiesterase

  • they are positive allosteric modulators of the GABA-mediation

  • they block D2 receptors in the CNS

Explanation

Question 64 of 108

1

Nonbenzodiazepines hypnotics that act at GABA-recptor are

Select one or more of the following:

  • Phenobarbital

  • Melatonin

  • Zolpidem (Stilnox)

  • Zopiclone (Imovan)

Explanation

Question 65 of 108

1

Adverse drug reaction of Zopiclone (Imovan) are

Select one or more of the following:

  • bitter or metallic taste in the mouth

  • behavioral changes

  • hypertension

  • hypoglycemia

Explanation

Question 66 of 108

1

Magnesium sulfate has sedative effects when administered

Select one or more of the following:

  • orally

  • parenterally

  • subcutaneously

  • by inhalation

Explanation

Question 67 of 108

1

Mechanism of action of antiepileptic drugs includes

Select one or more of the following:

  • enhancing GABA synaptic transmission

  • blocking D2 receptors

  • reducing cell membrane permeability to calcium T-channels

  • reducingg ccell membrane permeability to sodium channels

Explanation

Question 68 of 108

1

Drugs reducing cell membrane permeability to voltage-dependent sodium channels are

Select one or more of the following:

  • Carbamazepine

  • Benzodiazepines

  • Lamotrigine

  • Valproate

Explanation

Question 69 of 108

1

Cell membrane permeability to calcium T-channels is reduced by

Select one or more of the following:

  • Valproate

  • Ethosuximide

  • Phenobarbital

  • Levetiracetam

Explanation

Question 70 of 108

1

What are the clinical indications for prescribing Carbamazepine?

Select one or more of the following:

  • It is a drug of first choice or focal and secondary generalized epilepsy

  • It is appropriate for treatment of absence seizures

  • It is used in the treatment of insomnia

  • It is useful for treatment of trigeminal neuralgia

Explanation

Question 71 of 108

1

What is characteristic of Phenytoin?

Select one or more of the following:

  • It reduces cell membrane permeability to voltage-dependent sodium channels

  • It increases GABA synaptic transmission

  • It is a potent enzyme inducer

  • It is also used as an antiarrhythmic drug

Explanation

Question 72 of 108

1

Adverse drug reactions of Valproates are

Select one or more of the following:

  • constipation

  • weight gain

  • hair loss

  • hepatotoxicity

Explanation

Question 73 of 108

1

Which antiepileptic drugs can be used for treating status epilepticus?

Select one or more of the following:

  • Benzodiazepines

  • Carboxamides

  • Valproates

  • Barbiturates

Explanation

Question 74 of 108

1

Muscarinic cholinergic receptors are located in:

Select one or more of the following:

  • skeletal muscles

  • bronchial smooth muscles

  • heart

  • smooth muscles of GIT

Explanation

Question 75 of 108

1

Nicotinic cholinergic receptors are located in:

Select one or more of the following:

  • autonomic ganglia

  • adrenal gland medulla

  • heart muscle

  • skeletal muscles

Explanation

Question 76 of 108

1

Pharmacological effects of Acetylcholine are:

Select one or more of the following:

  • bradycardia

  • tachycardia

  • increased digestive (abundant saliva), bronchial, cutaneous, (sweat) and lacrimal secretions

  • increased tone and peristaltic contractions of GIT

Explanation

Question 77 of 108

1

M-receptor agonist used for treatment of glaucoma is:

Select one or more of the following:

  • Atropini sulfas

  • Pilocarpini hydrochloridum

  • Neostigmini methylsulfas

  • Galantamini bromidum

Explanation

Question 78 of 108

1

What are the effects of Pilocarpine after eye application?

Select one or more of the following:

  • mydriasis

  • miosis

  • increases the intraocular pressure

  • decreases the intraocular pressure

Explanation

Question 79 of 108

1

Acetylcholine esterase inhibitors (anticholinesterases) are:

Select one or more of the following:

  • lpratropii bromidum

  • Galantamine bromidum

  • Neostigmine methylsulfas

  • Pyridostigmine bromidum

Explanation

Question 80 of 108

1

Anticholinesterases are contraindicated in:

Select one or more of the following:

  • bronchial asthma

  • paralytic ileus

  • epilepsy

  • bradycardia

Explanation

Question 81 of 108

1

Antimuscarinic receptor antagonists are:

Select one or more of the following:

  • Atropini sulfas

  • Butylscopolamine

  • Atracurium besilas

  • Ipratropium bromidum

Explanation

Question 82 of 108

1

Pharmacological effects of antimuscarinic drugs are:

Select one or more of the following:

  • tachycardia

  • intestinal smooth muscle relaxation

  • mydriasis

  • decrease the secretion of exocrine glands

Explanation

Question 83 of 108

1

Clinical indications for prescribing antimuscarinic drugs are

Select one or more of the following:

  • bronchial asthma

  • spasm of the smooth muscles of GlT

  • to elicit papillary dilation

  • glaucoma

Explanation

Question 84 of 108

1

Adverse drug reactions of Atropine are:

Select one or more of the following:

  • dry mouth

  • tachycardia

  • difficulties in seeing close objects

  • disorientation and hallucinations

Explanation

Question 85 of 108

1

Adverse drug reactions of non-depolarizing muscle relaxants are:

Select one or more of the following:

  • histamine release

  • hypotension

  • hypertension

  • allergic reaction

Explanation

Question 86 of 108

1

Which of the following drugs will antagonise the effect of the non-depolarizing neuromuscular blockers?

Select one or more of the following:

  • Anticholinesterases

  • MAO inhibitors

  • Antimuscarinic agents

  • Aminoglycoside antibiotics

Explanation

Question 87 of 108

1

What are the main features of Suxamethonium chioridum:

Select one or more of the following:

  • short-lasting effect

  • has no antagonist

  • anticholinesterases prolong its effect

  • oral administration

Explanation

Question 88 of 108

1

α1-adrenoceptors are located on:

Select one or more of the following:

  • presynaptic neuronal endings

  • postsynaptic neuronal endings

  • blood vessels

  • iris dilator muscle

Explanation

Question 89 of 108

1

β1-adrenoceptors are located on:

Select one or more of the following:

  • postsynaptic neuronal endings

  • presynaptic neuronal endings

  • myocardial cells

  • juxtaglomerular apparatus in the kidney

Explanation

Question 90 of 108

1

β2-adrenoceptors are located on:

Select one or more of the following:

  • postsynaptic neuronal endings

  • bronchial smooth muscles

  • liver

  • uterus (womb)

Explanation

Question 91 of 108

1

Indications for the clinical use of Epinephrine are:

Select one or more of the following:

  • anaphylactic shock

  • hypoglycemia

  • arrhythmia

  • glaucoma with wide iridocorneal angle

Explanation

Question 92 of 108

1

Pharmacological effects of the selective β2-agonists are:

Select one or more of the following:

  • pupillary dilation

  • bronchial dilation

  • blood pressure elevation

  • relaxation of uterine muscle

Explanation

Question 93 of 108

1

Which of the following drugs are selective β2-agonists?

Select one or more of the following:

  • lsoprenalini sulfas

  • Orciprenalini sulfas

  • Salbutamol

  • Salmeterol

Explanation

Question 94 of 108

1

β2-agonists are indicated in:

Select one or more of the following:

  • bronchial asthma

  • digitalis intoxication

  • arterial hypertension

  • threatening abortion

Explanation

Question 95 of 108

1

Adverse drug reactions of β2-agonists are:

Select one or more of the following:

  • finger tremor

  • bronchial dilatation

  • hyperglycemia

  • tolerance

Explanation

Question 96 of 108

1

Which of the following drugs act as agonists of the presynaptic α2-adrenoceptors?

Select one or more of the following:

  • Salbutamol

  • Clonidini hydrochloridum

  • α-Methyldopum (Dopegyt)

  • Sotalol

Explanation

Question 97 of 108

1

Adverse drug reactions of Clonidin are:

Select one or more of the following:

  • Dry mouth

  • Drowsiness and depression

  • Hypertensive attacks following abrupt cessation of treatment

  • CNS stimulation

Explanation

Question 98 of 108

1

For Methyldopa is true:

Select one or more of the following:

  • has antihypertensive effect

  • it is safe in pregnancy

  • could cause drug-induced parkinsonism

  • used to treat threatening abortion

Explanation

Question 99 of 108

1

Which of the following drugs are selective β1-blockers?

Select one or more of the following:

  • Atenolol

  • Pindolol

  • Propranolol

  • Metoprolol

Explanation

Question 100 of 108

1

β-blockers are indicated in case of:

Select one or more of the following:

  • hypertension

  • bronchial asthma

  • arrhythmia

  • ischaemic heart disease

Explanation

Question 101 of 108

1

β-blocker approved for topical use in treatment of glaucoma is:

Select one or more of the following:

  • Bisoprolol

  • Metoprolol

  • Timolol

  • Propranolol

Explanation

Question 102 of 108

1

Potential adverse drug reactions of β-blockers are

Select one or more of the following:

  • hypoglycaemia

  • bronchoconstriction

  • hyperglycaemia

  • nightmares

Explanation

Question 103 of 108

1

Effects of methylxanthines on the cardio-vascular system are:

Select one or more of the following:

  • positive inotropic effect

  • negative inotropic effect

  • increased cardiac output

  • cranial vessels constriction

Explanation

Question 104 of 108

1

Adverse drug reactions of methylxanthines are:

Select one or more of the following:

  • arrhythmia

  • seizures - in higher doses

  • increased oxygen demand of the heart

  • bronchial constriction

Explanation

Question 105 of 108

1

Therapeutic uses of Methylehenidaie are:

Select one or more of the following:

  • attention deficit hyperactivity disorder (ADHD) in children

  • hypertension

  • narcolepsy

  • concentration and attention deficit in adults

Explanation

Question 106 of 108

1

Antidepressants, selective serotonin reuptake inhibitors are:

Select one or more of the following:

  • Fluoxetine

  • Clomipramine

  • Paroxetine

  • Amitriptyiine

Explanation

Question 107 of 108

1

Mode of action of antidepressants involves:

Select one or more of the following:

  • Inhibition of serotonin reuptake

  • Inhibition of norepinephrin reuptake

  • Stimulation of serotonin reuptake

  • MAO inhibition

Explanation

Question 108 of 108

1

In treatment with MAOIs should be avoided the intake of:

Select one or more of the following:

  • tyramine containing nutrition

  • cyclic antidepressants

  • adrenomimetics

  • cholinolytics

Explanation