Written Pharmacology Flashcards
2 Adverse Effects of Penicllins:
Allergic Reactions: angioedema & Anaphylactic shock
CNS irritation (seizures) may occur with large doses in patients with renal failure
Discuss Toxicity of Cephalosporins (Cef-)
3-Irritant: - I.M. → Painful, so add lidocaine.
4- Nephrotoxicity
Biliary sludge due to insoluble salts in bile
Explain the manifestations of Aminoglycoside (-mycin) toxicity
1.Ototoxicity:
a. Irreversible damage of 8th cranial nerve leading to vertigo & deafness
- Nephrotoxicity:
a. It is usually reversible. - Neuromuscular blockade: It is rare. may result in respiratory muscle paralysis
- Allergic reactions
2 Adverse effects of macrolides (-thromycin or -micin)
Cholestatic Jaundice
Epigastric pain
2 adverse effects of fluoroquinolones (-floxacin)
Photosensitivity
Nephrotoxic
2 adverse effects of Sulfonamides (sulfa-)
Bone marrow inhibition
Stevens-Johnson syndrome in allergy
Two Adverse Effects Rifampicin
Orange-red discoloration of secretions
Allergy → Flu-like syndrome.
Drug interactions of Rifampicin
Hepatic Microsomal Enzyme Inducer→↑ Metabolism of Oral anti-coagulants contraceptives, corticosteroids
2 adverse effects of I.N.H (Isoniazid)
Peripheral neuritis
Hepatotoxicity
Antibacterial Activity of Penicillins
Penicillins: Penicillin G is the prototype (narrow spectrum): All positive cocci, anaerobes, spirochetes, actinomycetes
Extended spectrum Penicillin: Aminopenicillins; gram -ve and Anti-pseudomonal
Therapeutic uses of penicillins
treatments of infections by gram +ve Cocci, gram -ve cocci, gram +ve Bacilli, spirochetes and actinomycosis
Gram -ve bacilli, and pseudomonas
Prophylactic uses: for streptococcal infection in Rheumatic fever, bacterial endocarditis and Gonorrheal neonatal ophthalmia
4 therapeutic uses of cephalosporins
Gram negative meningitis
Gonorrhea
Typhoid fever
UTI
Preparations and Uses Aminoglycosides:
А) Systemic use:
1. Used in serious gram-negative infection and Staphylococcal & Enterococcal infections.
- Bacterial endocarditis. Add Benzyl penicillin.
B) Topical uses:
1. Topical neomycin, in burns, wounds & skin lesions.
2. Oral neomycin for gut decontamination:
C) Uses in TB Streptomycin
4 Therapeutic Uses of Macrolides (-thromycin)
Diphtheria infection
Chlymadia infection
Gonorrheal infection
Syphilitic infection
Therapeutic uses of fluoroquinolones (-floxacin)
- Infections of urogenital caused by gram-negative organisms.
- Respiratory, skin & soft tissue infection.
3 Resistant T.B
5.Typical & atypical pneumonia
Therapeutic Uses of co–trimoxazole (sulfamethoxazole)
1, Respiratory tract infection.
2. Urinary tract infection (UTI).
3. Prostatitis.
4. Salmonella
MOA of Anti-Bacterial Activity of B-lactams : bactericidal
1- They bind to specific Penicillin-Binding-Protein (PBP):
a- y Transpeptidase enzyme responsible for cross-linking of peptidoglycans, a final step in cell wall synthesis → Cell Wall Synthesis.
b-Activate Autolytic enzymes (Autolysins) → Lysis of cell wall.
c- Bacteria imbibe water due to its interior high osmotic pressure → Rupture and DEATH of the microbe.
Explain Antibacterial action of sulphonamide (Sulf-)
Compete with PABA Dihydropteroate synthetase (DHPS) I Folic acid synthesis. Folic acid is essential for synthesis of bacterial purines & DNA.
Anti-Bacterial Activity of Rifampicin
↓ DNA-dependent RNA polymerase enzyme ↓ Synthesis of RNA
Anti-Bacterial Activity of I.N.H. (Isoniazid)
↓ Mycolic acid synthesis —> decrease synthesis of Cell Wall
Mech of action of amphotericin B
Amphotericin B binds to ergosterol in the fungal cell membrane → forming amphotericin B-associated pores in the cell membrane → ↑ permeability of the fungal cell → leakage of fungal cell contents.
Therapeutic uses of amphotericin B
1-Fungal meningitis
2- Fungal pneumonia.
3- Systemic candidiasis
2 adverse effects of amphotericin B
Nephrotoxicity
Seizures after intrathecal administration
Mechanism of action of Azoles (Imidazole)
Inhibit fungal CYP 450 → inhibition of synthesis of ergosterol of fungal cell membrane from lanosterol.
2 Imidazole uses
dandruff
Oral thrush
Mechanism of action Nucleoside reverse transcriptase inhibitor (NRTIs) (-vudine)
mammalian DNA polymerase is relatively resistant.
Mechanism of action Non-Nucleoside reserve transcriptase inhibitors (NNRTIs) (-virine)
Bind to reverse transcriptase near the catalytic site→ denaturation of reverse transcriptase → inhibition of viral DNA production.
MOA of Protease Inhibitors (PIs) (-navir)
Inhibit specific viral protease enzyme essential for cleavage of the synthesized non-functional polyproteins into functional viral proteins.
Mechanism of Action of insulin:
Insulin binds to the a-subunit of tyrosine kinase receptors, → Activation of tyrosine kinase activity of B – subunit → Phosphorylation of intracellular proteins → Change in enzyme activity, gene expression and translocation of Glut-4 transporter→ Glucose uptake by adipose tissue & Skin.
Indications of insulin:
A) Diabetes Mellitus:
1- Type-1 diabetics, all cases of Insulin Dependent Diabetes Mellitus (IDDM)
2- Type2(NIDDM)
3- Emergency treatment of Diabetic Ketoacidosis& Non-ketotic Hyperosmolar Diabetic coma.
B) Other Indications: Hyperkalemia due to renal failure.
Adverse Effects of Insulin:
Hypoglycemia
Hypokalemia
Somogyi Effect > Rebound morning hyperglycemia.
Amylin analog : Pramlintide (Symlin) mechanism of action
i. Reduces glucagon secretion
ii. Delays gastric emptying
iii. Decreases appetite.
Amylin analog Uses:
Used SC in patients with Type 1 or Type 2 diabetes who have problems with postprandial hyperglycemia.
Amylin analog Adverse effects:
anorexia
hypoglycemia
Sulfonylurea (Gly- or Gli-) Mechanism of Action
1- Increase insulin release from the pancreas:
They Block ATP-sensitive K-channel→ Depolarization → Influx of Ca → Exocytosis → ↑Release of Insulin.
2- Other actions (Extra-pancreatic): may increase peripheral insulin sensitivity.
Indications of Sulfonylureas (Gly- or Gli-):
Type-2 Diabetes (NIDD) after failure of Diet regulation &exercise.
a- Non-Obese
b- Non-Complicated Diabetes:
- No stress
- No Major organ disease
Adverse Effects of Sulfonylureas (Gly- or Gli-):
a- Hypoglycemia
b- Weight gain
Mechanism of action of biguanides (-formin; metformin)
1- The primary effect is to reduce hepatic glucose production by activating the enzyme AMP-dependent protein kinase (AMPK). This leads to stimulation of hepatic fatty acid oxidation, glucose uptake, and nonoxidative glucose metabolism and reduction of lipogenesis and gluconeogenesis &glycogenolysis.
Therapeutic Uses of Metformin
● Type 2 , in overweight patients, when dietary management and exercise alone do not result in adequate glycemic control.
● A reduction of diabetic complications after failure of diet
Adverse Effects of Biguanides (-formin; metformin)
↓ absorption of Vitamin B-12.
Rarely fatal Lactic Acidosis may occur so
Mechanism of action of GLP-1 analogues (-glutide)
1- Synthetic analogs of Glucagon-like Peptide-1 → Bind to GLP-1 receptors → reduce postprandial glucose elevation and glucagon levels, delay gastric emptying, ↑ insulin release & and suppress appetite
Uses GLP-1 analogue (-glutide)
1- control glycemia in patients with type 2 diabetes who fail to achieve control via metformin and/or sulfonylureas.
2- Liraglutide for weight loss.
Disadvantages GLP-1 analogues (-glutide)
Pancreatitis
renal impairment and acute renal injury may occur
DPP-4 (-gliptin) mechanism of action
release of (DPP-4) enzyme leading to prolongation of the action of endogenously released glucose independent peptide
Adverse Effects of DDP-4 (-gliptin)
1- Infrequent pancreatitis
2- increase risk of heart failure
SGLT2 INHIBITORS (-gliflozin) Mechanism of action
inhibiting this transporter will result in glucose excretion of only 30- 50% of the amount filtered causing glycosuria and lowers glucose levels in patients with type 2 diabetes.
Clinical indication of SGLT-2 inhibitors (-gliflozin)
Used as 3rd line therapy for type 2 DM
SGLT-2 inhibitors (-gliflozin) Adverse effects:
- Genital & urinary tract infections
- Hypotension
Mechanism of action of thyroid hormones:
- T3 and T4 dissociate from Thyroxine-binding globulin (TBG) and enter cells by diffusion or active transport.
- Inside the cell, T4 deiodinated to T3
- T3 enters the nucleus and attaches to its nuclear receptor
- Drug-receptor complex bind to DNA and promotes transcription of specific gens mRNA formation → synthesis (production of various enzymes).
Therapeutic Uses of Thyroid Hormones:
- Replacement therapy in hypothyroidism
- TSH suppression therapy in thyroid cancer and nontoxic goiter.
Mechanism of Action Thioamides (Propylthiouracil)
- Inhibition of oxidation of iodide to iodine.
- Inhibition of iodination of tyrosine
- Inhibition of coupling of iodotyrosines to T4 and T3.
- Propylthiouracil in addition reduces conversion of T4 to T3 in the periphery.
Therapeutic uses Thioamides (Propylthiouracil)
- As principal therapy.
- As adjuvant to I 131 to control the disease while waiting its effect.
- To control the disorder in preparation for surgical treatment.
- Thyroid storm
Adverse effects of Thioamides (Propylthiouracil)
Hepatotoxicity
Immunological reactions: lymphadenopathy
Iodides Mechanism of action :
- Inhibition of iodide organification
- Reduction of the response of thyroid gland to TSH,
- Inhibition Release of T3& T4.
Iodides Therapeutic indications :
Preparation of the patient for thyroidectomy
Prophylactic where goiter is endemic.
Iodides Adverse effects
- iodism: metallic taste, painful salivary glands, excess salivation, running eyes &nose.
- Allergic reactions: angioedema, rash, drug fever
Therapeutic uses of estrogens
- Contraception with progestogens.
- Postmenopausal hormonal therapy(HT):
- Replacement therapy:
a. 1ry hypogonadism (ovarian failure).
b. Premature menopause
c. Surgical menopause
Adverse Effects of estrogens
Thromboembolic events
myocardial infarction.
Therapeutic uses of progestins
- Oral contraception: alone or with estrogen
- Functional uterine bleeding.
- Dysmenorrhea, Amenorrhea, Endometriosis.
Adverse Effects of progestins
Edema
Psychic depression.
Uses of androgens
Replacement therapy in male 1ry hypogonadism
Adverse effects of androgens:
masculinization in females, hirsutism
early puberty and premature closure of epiphyseal plates in children.
Mechanism of action of cortisol
Binds to cytoplasmic glucocorticoids receptor—> activation—> receptor hormone complex —> acts as a transcription factor to express or repress genes
Uses of Glucocorticoids
A) Replacement therapy in adrenocortical insufficiency (Addison’sdisease) :
a) Acute Addisonian Crisis:
b) Chronic Addison’s Disease:
B) Supplementary & Suppressive therapy
1. Anti-Inflammatory
2. Allergic diseases
3. Immunosuppressive in: Auto-immune diseases
4. shock and stress conditions
Adverse Effects of Glucocorticoids:
Moon face & Buffalo hump
Cataract & increases intra-ocular pressure ›-Glaucoma.
Na retention: Edema and Hypertension
Contraindications of Glucocorticoids
Hypertension
Peptic ulcer.
Glaucoma
Calcitonin Action:
- Hypocalcemic hormone
- Decreases Ca++ level in the blood
1) Bone: inhibits osteoclastic activity so, it decreases bone resorption.
2) Kidney: inhibits calcium and phosphate reabsorption by the kidney tubules
Calcitonin 2 uses
- relief of pain associated with osteoporotic fracture.
- may be beneficial in patients who have recently suffered a vertebral fracture.
Action of biphosphonates
decrease osteoclastic bone resorption
Adverse effects of biphosphonates:
Esophagitis and esophageal ulcers.
Adverse Effects of Vancomycin
Nephrotoxic.
Rapid VI infusion →Histamine release → Red man syndrome & Shock.
Adverse Effects of Tetracyclines (-cycline)
- Teeth & Bone Abnormalities
- avoided during pregnancy, and lactation & in children up to 18 years. - Hepatotoxicity during pregnancy
Adverse Effects of Co-trimoxazole
Allergy
Nephrotoxicity
Therapeutic Uses of Vancomycin
- IV in MRSA & Enterococcal infections.
- IV prophylactic before dental operations in patients with prosthetic valves.
- Orally in pseudomembranous colitis.
Therapeutic Uses of Tetracyclines (-cycline)
Sinusitis
Amoebic dysentery
Acne
Cholera
Therapeutic Uses of Rifampicin
- First line drug in T.B.
- Leprosy.
- Drug of choice in prophylaxis of Meningococcal meningitis
Mechanism of Action of Vancomycin
Inhibits early steps of Cell wall synthesis →Peptidoglycan polymerization →Bactericidal.
Mechanism of Action of Aminoglycoside :
- They bind to 30 S ribosomal subunit leading to inhibition of bacterial protein synthesis
4 uses of benzodiazepines (-azepam)
Anti epileptic
Anti convulsant
Anti anxiety
Anti depressant
Anesthesia
2 adverse effects of benzodiazepines (-azepam)
Sedation
Addiction
SSRI (-oxetine) 4 uses and two adverse effects
Eating disorder (AE anorexia)
Depression (Serotonin syndrome)
PTSD
Panic
MOA of L-Dopa
L-DOPA by Central Dopa Decarboxylase →Dopamine > increase D2 receptors
L-Dopa uses
treats all manifestation of Parkinsonism by tremors by stimulating D2 receptors in basal ganglia
L-Dopa side effects
Severe rigidity
Delusions and hallucinations
Anti-epileptics MOA
Increase inhibitory trans (GABA)
decrease excitatory (glutamate)
Phenytoin uses
Grand mal partial seizures
Status Epilepticus
MOA and USES of Carbamazepine (-azepine)
Blocks Na channels, thereby inhibiting repetitive action potentials in epileptic focus
Uses:
Grand Mal Epilepsy & Partial seizures
Trigeminal neuralgia
Mood stabilizer
Adverse effects of Carbamazepine (-azepine)
Steven-johnson syndrome
Bone marrow inhibition
Phenytoin adverse effects
Convulsions
Vertigo
Morphine MOA and USES
Morphine stimulates specific Opioid= Opiate receptors in CNS & Periphery
Uses: Cancer pain, Colic pain ,Cardiac Pain, Post operative pain
Morphine adverse effects
Pin point pupil (PPP)
Inhibition of Respiration
Interfere with proper diagnosis of Head injury
Aspirin (Salicylates) actions and uses
Anti-inflammatory—–> superficial pains
Anti- Rheumatic—–> for arthritis
Anti-platelet—–> thromboembolic disease
Increase uric acid secretion—–> chronic gout
MOA of Aspirin (Salicylates):
irreversible inhibition of COX enzyme (1,2,3) by acetylation.
MOA of paracetamol and uses
- Inhibit COX-3 in C.N.S. Mainly Anti-pyretic Analgesic →As potent as Aspirin.
Allergy to aspirin, bronchial asthma, peptic ulcer
Adverse Effects of Paracetamol
Nephrotoxicity
Allergy
Therapeutic Uses of Colchicine
- Useful when NSAIDs & corticosteroids are contraindicated or not tolerated.
- Prophylaxis of Gout
- Prophylaxis of Familial Mediterranean Fever
MOA of Allopurinol
- Allopurinol is metabolized by Xanthine Oxidase enzyme (XOE) → Aloxanthine.
- Both Alopurinol & Aloxanthine →Occupy & inhibits X.E. →deceases Synthesis of uric acid.
Uses of Allopurinol
Gouty nephropathy
urate renal stones.
Adverse Effects of Allopurinol
Allergic skin reaction (mainly rash)
Hepatomegaly.
Adverse effects and toxicity of LA:
A- Systemic toxicity:
- CNS
a. restlessness, tremors.
b. This is followed by respiratory depression, coma, and death from respiratory failure. - Cardiovascular system
a. Bradycardia.
b. Hypotension
B- Local toxicity
1. Nerve damage →prolonged sensory &motor loss.
2. Tissue damage →necrosis due to VC by adrenaline added to LA.
C- Toxicity of spinal anaesthesia:
a. Hypotension
b. Treatment by leg elevation - I.V. fluid - sympathomimetics.